ANTICANCER RESEARCH 32: 1843-1966 (2012)

ABSTRACTS OF THE 22nd ANNUAL

MEETING OF THE ITALIAN SOCIETY
OF URO-ONCOLOGY (SIUrO)

13-15 June, 2012,

Bologna, Italy
Savoia Hotels Bologna,
Via del Pilastro, 2,
Bologna, Italy

Chair:
Giuseppe Martorana

Local Scientific Committee:

Enza Barbieri
Fulvio Colombo
Stefano Fanti
Walter Grigioni
Andrea Martoni
Renzo Mazzarotto
Giuseppe Severini
 Local Organizing Committee:

Alessandro Bertaccini
Eugenio Brunocilla
Marco Garofalo
Fabio Manferrari
Riccardo Schiavina

Rinaldo Beghelli
Sergio Concetti
Claudio Ferri
Michele Lo Cigno
Vincenzo Tomaselli

Alessandro Franceschelli

Referees of Abstracts

V. ALTIERI, Naples, Italy A. LAPINI, Florence, Italy

R. AUTORINO, Naples, Italy N. LONGO, Naples, Italy
C.S. BALBI, Genova, Italy M. MAFFEZZINI, Genova, Italy
V. BALDAZZI, Firenze, Italy C. MAGNO, Messina, Italy
P. BARBORO, Genova, Italy D. MARCHIORI, Bologna, Italy
A. BERTACCINI, Bologna, Italy G. MARTORANA, Bologna, Italy
A. BILANCIO, Napoli, Italy F. MASSARI, Verona, Italy
E. BOLLITO, Orbassano, Italy F. MENGONI, Bologna, Italy
S. BRAVACCINI, Meldola, Italy C. ORTEGA, Turin, Italy
M. CARINI, Firenze, Italy G.L. PAPPAGALLO, Mirano, Italy
R. CECCARELLI, Bologna, Italy C. PATRIARCA, Milano, Italy
L. CINDOLO, Benevento, Italy P. PAVLICA, Bologna, Italy
R. CIVIDINI, Bologna, Italy D. PREZIOSO, Napoli, Italy
R. COLOMBO, Milano, Italy D. ROMAGNOLI, Bologna, Italy
G. DI LORENZO, Naples, Italy G. SANGUINETI, Milano, Italy
M. FALSAPERLA, Catania, Italy V. SCATTONI, Milan, Italy
A. FANDELLA, Treviso, Italy V. SERRETTA, Palermo, Italy
G. FELLIN, Trento, Italy G. SICA, Rome, Italy
A. FORNARI, Turin, Italy M.S. SQUEO, Turin, Italy
F. FRANCESCA, Pisa, Italy V. VAGNONI, Bologna, Italy
M. GIAMPAOLI, Bologna, Italy R. VALDAGNI, Milano, Italy
R. HURLE, Bergamo, Italy S. VILLA, Milan, Italy
B. JERECZEK, Milan, Italy A. VOLPE, Novara, Italy
Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

Italian Society of Uro-Oncology (SIUrO)

President: Giuseppe Martorana, Bologna, Italy

Board

PRESIDENT: Giuseppe Martorana

VICE PRESIDENT: Riccardo Valdagni
PAST PRESIDENT: Raffaele Tenaglia
Secretary General & Treasurer: Alessandro Bertaccini
INCOMING PRESIDENT: Giario Conti

Advisors

Enrico Bollito
Sergio Bracarda
Renzo Colombo
Alberto Lapini
Nicola Longo
Massimo Maffezzini
Gigliola Sica
Cora Sternberg

Elected Scientific Committee

PRESIDENT: Gigliola Sica

Members
Vincenzo Altieri
Vincenzo Scattoni
Giovanni Pappagallo

Scientific Secretariat
Società Italiana di Urologia Oncologica (SIUrO)
c/o Clinica Urologica, Alma Mater Studiorum
Università di Bologna, Policlinico S. Orsola - Malpighi
Padiglione Palagi, via P. Palagi, 9 – 40138 Bologna
Tel: +39 051 349224 - 051 6362421– Fax: +39 051 308037
e-mail: congresso@[Link] – web: [Link]

Organizing Secretariat
Emilia Viaggi Congressi & Meeting S.r.l.
Via Porrettana, 76, 40033 Casalecchio di Reno (BO)
Tel: +39 051 6194911 – Fax: +39 051 6194900
e-mail: evcongressi@[Link] – web: [Link]

Savoia Hotels Bologna, Via del Pilastro, 2, 40127 Bologna

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ANTICANCER RESEARCH 32: 1843-1966 (2012)

This article is freely accessible online. were acceptable. Mayor complications were correlated with
high ASA score (3-4), urinary diversion (Bricker) and surgical
1 approach (peritoneal route).
EXTRAPERITONEAL RETROGRADE
RADICAL CΥSTECTOMY (RC) IN THE
ELDERLY: LONG TERM RESULTS 2
RADICAL PROSTATECTOMY (RP) WITH
Maurizio A. Brausi, Mirko Gavioli, GianLuca Simonini,
EXTENDED PELVIC LYMPHADENECTOMY
GianCarlo Peracchia, Giuseppe De Luca, Massimo Viola,
(EPLND) FOR PT3B-T4 PROSTATE CANCER (PCA):
Giorgio Verrini, Romano Alberto
LONG-TERM RESULTS OF A SINGLE CENTRE
Dept. of Urology AUSL, Modena, Italy
M.A. Brausi, G. De Luca, M. Gavioli, G. Peracchia,
G. Verrini, M. Viola, A. Romano, G. Simonini
Objectives: Τo evaluate morbidity, overall (OS) and disease
specific survival (DSS) of RC in octogenarians according to Dept. of Urology AUSL, Modena, Italy
surgical approach (peritoneal vs. extraperitoneal), ASA score,
and type of urinary diversion in the long term. Methods: From Introduction and Objectives: RP+EPLND has been suggested
2000 to 2007 105 pts 80 year-old or older received RC and as a possible treatment option in patients with cT3 Pca by
urinary diversion for BC at our institution. The mean age was different groups. Few very long term data exist on the fate of
83.2 years: 73 men and 32 women. 88/105 (83.9%) pts had one pT3b-T4 Pca patients treated by RP+ EPLND. The objectives
or more comorbidities. ASA score was used for classifying of this study were to evaluate the oncological outcomes of
preop. risk. 21/105 (20%) were ASA 2, 55/105(52.4%) ASA 3 pT3b-T4 Pca patients >9 years after radical surgery and to
and 29/105 (27.6%) ASA 4. 40/105 pts (38%) received observe side-effects. Patients and Methods: From March 2000
RC+lymphadenectomy through a peritoneal approach, while to December 2005, 602 radical prostatectomies were performed
65/105 pts (62%) had a retrograde extra-peritoneal RC. 53/105 by a single surgeon. 105/602 pts. (17.4%) were staged as
(50.5%) had uretero-cutaneostomy (UCS) as diversion, while clinical T3. After surgery 40/105 pts. were pT3b (31) or T4 (9).
38/105 (36.2%) had Bricker.14/105 pts (13.3%) had an The mean age was 68.1 (range 51-76) and the mean pre-op PSA
orthotopic neobladder. Pathological stage was: Recurrent was 24.5 ng/ml (range 4-130 ng/ml). All the pts. were Mo
Tis+T1 in 11/105 pts (10.4); T2b in 15/105 (14.3%); T3a in (negative CT and bone scan). Surgery: a bilateral EPLND was
24/105 (22.8%); T3b in 37/105 (35.2%); T4 in 18/105 (17.1%). always performed. The number of nodes removed varied from
23/105 patients (21.9%) were N+(pT3-T4). 81/105 patients 20 to 45 (mean 32.5). The retrograde extraponeurotic approach
(77.2%) were in intensive care unit for 1-6 days. 51/105 with removal of Denonviller fascia was used. Nerve sparing was
patients (48.6%) were transfused. Results: The mean follow- never attemped. Additional surgical margins of the prostatic
up was 46.5 months (24-96 months). Perioperative mortality fossa (bladder neck, lateral, base and urethra) were taken after
was 8.5% (9/105). Mean hospital stay was 14.5 days (7-35 RP for a more complete staging. Results: P Stage: p T3b=31, p
days). The complication rate (medical and surgical) was 36%. T4=9. Grade: Gleason score <6=2 (5%), Gleason score 7=7
8.3% of patients required a second operation. Medical and (17.5%), Gleason score 8-10=28 (70%). Grade
surgical complications by ASA were: ASA2=11.8%, ASA undetermined=3pts. 30/40 pts. (92.5%) had positive margins
3=(50%), ASA4=38% respectively. Complication rate while 26/40 pts. (65%) had positive nodes: 20/31(64.5%) in
according to surgical approach: Medical: extraperitoneal pT3b and 6/9 (66.6%)in pT4. Mean follow-up was 110.3
40.4%, peritoneal 27%.Surgical:12.8% with extra-peritoneal months (range 86-140 mos). 2 pts. were lost to follow-up and 1
route vs. 29.7% with intra peritoneal approach. Re-operation pt. died after 15 days from surgery due to pulmonary embolus.
rate: Extraperitoneal=0.9% vs. 7.6% peritoneal. Mean blood 37 pts were followed regularly. Of these 25 (67.6%) received
loss was: 380 cc in extraperitoneal vs. 780 cc in the immediate adjuvant Hormone Therapy (HT) after RP. 2 pts. had
intraperitoneal approach. Complications according to diversion: Radio (RT)-Chemotherapy+ HT and 2 pts RT+ HT. Overall
Medical=45% in UCS vs. 34.5% in Bricker vs. 39.5% in survival was 57.5% (23/40 pts.). 18/40 were T3b (47.5%) and
orthotopic. Surgical: 24% UCS vs. 34.5% Bricker vs. 37% in 4/40 T4 (10). DSS was 75% (30/40 pts.): 23 were pT3b (57.5)
orthotopic. [Link] rate: UCS=0 vs. 17% in Bricker vs. 7.1 in and 6 pT4 (17.5%). 8/37 pts. received RP+EPLND alone: 4/8
orthotopic. 82 pts had regular long term follow-up. After 1 year pts. had an undetectable PSA (0.001-0.01 ng/ml), 3 had PSA of
OS was 60%, after 2 years 43.6% and after 3 year 39.9%. DSS 0.8,2.7 and 3.6 ng/ml; in 1 pt. PSA was not available. 11/25 pts.
was 63.3% after 1 year and 51.2% after 2 years and 50% after (44%) treated with immediate HT had an undetectable PSA
3 years. No difference in survival was seen between the extra (0.001-0.01 ng/ml), 9/25 pts (36%) had PSA progression (0.8-
or intra-peritoneal approach. Conclusion: The results of our 17.8 ng/ml) and died of the disease. Complications: mortality
study support the use of RC in octogenarians. Complications 1/40 (2.5%), Lymphoceles=35%. Rectal injuries=5% with

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

intra-op repair. Conclusion: The combination of RP+ EPLND Introduction: The advent of the PSA and the diffusion of
and HT +/–RT resulted a valid treatment option for pts. with screening programs for early detection of prostate cancer in
pT3b-T4 Pca. 9-year DSS was 75%. 10% and 27.5% of pts. recent years has led to an increase in the diagnosis of
with surgery alone and surgery + immediate HT had an microfocal prostate cancer (MPC). MPC is a small tumor that
undetectable PSA after 9 years. Larger studies are needed to involves less than 5% with Gleason 6 or less of the biopsy
confirm these results. specimen with a minimum of four glands cancer. The biopsy
and clinical parameters play an important role in risk and
treatment decisions. The objective of this study was to evaluate
3 retrospectively the clinical staging in patients with prostate
MIDDLE TERM FOLLOW-UP RESULTS OF mapping biopsy indicative of MPC, with PSA <10 and then,
MAGNETIC RESONANCE IMAGING EVALUATION once these patients underwent radical prostatectomy compare
AFTER FOCAL THERAPY FOR PROSTATE CANCER the results of the biopsy and clinical parameters before surgery
with definitive histological examination. Patients and Methods:
A. Losa1, G. Cardone2, M. Lazzeri1, G.M. Gadda1,
We examined retrospectively 78 patients (mean age 68 years,
G. Lughezzani1, E. Dell’Acqua1, A. Larcher1,
range 49-72) diagnosed with MPC, who subsequently
G. Lista1, G. Balconi2, G. Guazzoni1
underwent radical prostatectomy at our clinic between 2006 to
1Department of Urology, 2011. We analyzed PSA, PSA density, prostate volume, digital
2Department of Radiology, San Raffaele Turro Hospital, rectal examination, transrectal prostate ultrasound, and
Vita-Salute San Raffaele University, Milano, Italy compared these parameters with histopathological diagnosis,
Gleason score on biopsy and subsequent radical prostatectomy.
Introduction and Objectives: We report the mid-term MR Biopsies were performed by the same single high experienced
imaging follow-up in patients who underwent focal therapy center (more than 300 prostate biopsies/year). Patients
(FCA) for prostate cancer (Pca). Patients and Methods: Eleven underwent transrectal ultrasound guided prostate biopsy, with
patients with unifocal, low-grade (Gleason≤6) PCa were an average of 14 samples per procedure. The presence of an
selected with trans-perineal template-guided prostate biopsy. MPC was associated with high grade PIN in 72% of cases. The
All the patients were subsequently treated with FCA. Patients assignment of Gleason score was possible in 86.7% of the
were followed up by MR imaging 24 hours after surgery, and examined cases, while for 6 biopsy specimens grading was
subsequently at 3, 12 and 24 months, with a 1.5T MR system undetermined. The PSA values were 78% lower for 10 (range
using T1w, T2w and dynamic ce-FS T1w sequences. Results: 3-34), while 83% of tumors were clinically potentially
24 hours after FCA, T2w images showed heterogeneous iso- insignificant. Results: In all 78 patients who underwent surgery
hyperintensity of the treated area, with high signal intensity after radical prostatectomy with a diagnosis of an MPC,
and hypointense perilesional rim at 3, 12 and 24 months. Post prostate cancer was confirmed by histological analysis on the
treatment ce-FS T1w MR images showed ischemia of the sample. In four cases the diagnosis was confirmed as MPC. In
treated zone. MR examinations showed a mean decrease in 59 patients (75.5%) was then diagnosed with organ confined
size of treated areas of 30% at 3, 70% at 12 and 80% at 24 cancer, unilateral (32, pT2a and 27, pT2b), multifocal bilateral
months. All the patients had a stable PSA level at 24 months cancer in 19: of these two with extraprostatic extension (pT3a),
after treatment. MR imaging follow-up revealed no evidence one with a bladder neck infiltration (pT4) and one with positive
of nodal recurrence. Conclusion: MR can be a valid tool in the surgical margins. The evaluation of the biopsy Gleason score
follow-up of PCa treated with FCA and may be used in the has underestimated the degree in 9 cases (11.5%) and
early evaluation of the effectiveness of treatment. Further overestimated in 6 (7.6%). There were no statistically
studies with a higher number of patients and longer follow-up significant correlations found between pathological stage, PSA,
are required. number of biopsies, previous histological findings, prostate
volume, rectal exploration and transrectal ultrasound, while
there was a significant correlation between PSA density,
4 advanced age and increased clinical risk. Discussion and
COMPARISON BETWEEN MICROFOCAL Conclusion: While a micro focus of Gleason score 6 prostate
PROSTATE CANCER BIOPSY AND cancer on biopsy is commonly considered as a low risk disease,
HISTOPATHOLOGICAL EXAMINATION AFTER literature define a mean 20% risk of pathological upgrading
RADICAL PROSTATECTOMY: OUR EXPERIENCE and/or upstaging. In our experience, this percentage was about
24%, slightly higher than the average reported in the literature.
Lucio Dell’ Atti, Gian Rosario Russo
The majority of patients with biopsy finding of MPC have after
Urologia Azienda Ospedaliero-Universitaria Arcispedale S. surgery a diseas increased in volume, even if organ-confined,
Anna, Ferrara, Italy often with involvement of both lobes of the prostate (19%). The

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

diagnosis of MPC does not seem to be more predictive of minutes before the biopsy. The first intention was to obtain
clinically insignificant prostate cancer. Patients with Gleason 14 cores in all patients. A verbal numerical pain score (VNS)
score 6 microfocal prostate cancer should be counseled that from 0 (no discomfort) to 10 (severe pain) was suggested to
they may harbor more aggressive disease, especially when pre- the biopsied patients who were asked to separately evaluate
treatment clinical risk factors are present, such as advanced age the degree of pain associated with the procedure, through two
or high clinical prostate specific antigen density. scales VNS, one for the insertion of the probe and the
manoeuvres associated with it, the other only for the biopsy.
1 Hong SK, Na W et al: Prediction of pathological outcomes Results: Only in 6 patients we were unable to insert TRUS
for a single microfocal (≤3 mm) Gleason 6 prostate cancer probe, in 4 due to presence of fibrous anal and in 2 due to
detected via contemporary multicore (≥12) biopsy in men severe haemorrhoidal prolapse. The mean age of patients was
with prostate-specific antigen ≤10 ng/mL. BJU Int 108(7): 68 years (48-78), the value of the PSA was 8.2 (2.5-17.8),
1101-1105, 2011. total prostate volume 57 ml (36-135). The number of biopsies
2 Thong AE, Shikanov S et al: A single microfocus (5% or performed in each patient was 14 (6-21). The mean pain in
less) of Gleason 6 prostate cancer at biopsy – can we predict the visual numerical scales in patients was 3.3 (2-8) in the
adverse pathological outcomes?. J Urol 180(6): 2436-2440, first questionnaire, 2.1(1-7) in the second questionnaire. The
2008. 8% of patients (79/969) declared severe or unbearable pain
3 Harnden P, Naylor B et al: The clinical management of (score ≥7), 716 patients (74%) declared no pain at all. Only
patients with a small volume of prostatic cancer on biopsy: 21 patients would never repeat the same biopsy or would
what are the risks of progression? A systematic review and request a different type of anesthesia and 786 (81%) of them
metaanalysis. Cancer 112(5): 971-981, 2008. would repeat it in the same way. Analyzing the two
questionnaires, a difference in the tolerability of the
procedure is observed in the first questionnaire, but not in the
5 second questionnaire (p<0.001). The patients were
TOLERABILITY OF TRANSRECTAL PROSTATE homogeneous in terms of pain with regard to the values of
BIOPSY WITH USE OF LIDOCAINE SPRAY: SINGLE PSA and prostate gland volume. Also, patients aged >65
CENTER EXPERIENCE AFTER 4 YEARS years tolerate the procedure better in the two questionnaires
(average pain VNS was respectively 2.4 and 1.7). In the
Lucio Dell’Atti, Gianni Ughi, Giovanni Pietro Daniele,
elderly there is a change in the perception of pain, due to
Gian Rosario Russo
several factors such as the decrease in the number of
Urologia Azienda Ospedaliero-Universitaria Arcispedale S. nociceptors and nociceptive afferents responsible for the
Anna, Ferrara, Italy elevation of the threshold and tolerance of pain. Discussion
and Conclusion: In our experience, transrectal PB is generally
Introduction: Transrectal ultrasound guided prostate biopsy is well tolerated with LS as the only anesthesia. Our study
now a routine, outpatient, easy to learn, quick and simple suggests that the main elements of discomfort during the
method, but still surrounded by a number of side-effects most procedure are the introduction of ultrasound probe and its
frequently including pain and discomfort. In our view, an movements than the biopsy itself. This new technique is an
important component of the state of discomfort during the excellent alternative to those currently practiced by most
procedure is characterized by the tone of the anal sphincter urologists, causing a sharp reduction of anal sphincter tone
and obstruction intrarectal ultrasound probe that causes with better patient compliance and tolerability to the
pressure and stretching of muscle fibers and sensory nerve ultrasound probe in the performance of biopsies.
fibers. The aim of our study was to evaluate patients tolerance
to transrectal ultrasound guided prostate biopsy using 1 Hergan L, Kashefi C and Parsons JK: Local anesthetic
anesthesia with Lidocaine Spray(LS). Patients and Methods: reduces pain associated with transrectal ultrasound-guided
Between September ‘07 and August ‘11, 975 consecutive prostate biopsy: a meta-analysis. Urology 69(3): 5205, 2007.
male patients with elevated PSA and (or) abnormal digital 2 Dell’Atti L and Daniele C: Lidocaine spray administration
rectal and (or) suspect TRUS scheduled for prostate biopsy during transrectal ultrasound guided prostate biopsy
(PB) were randomized. For this examination “end-fire” multi- modified the discomfort and pain of procedure: Results of a
frequency convex probe and needle 18 Gauge were used. randomized clinical trial. Arch Ital Urol 82(1): 125-127,
Biopsy examinations were performed alternately by two 2010.
experienced operators. Each examination was performed after 3 Galosi AB, Minardi D, Dell’Atti L et al: Tolerability of
emptying the bladder, because in our opinion the bladder prostate transrectal biopsies using gel and local anesthetics:
repletion is an important element of discomfort during biopsy. results of a randomized clinical trial. J Endourol 19(6): 738-
All patients were treated with LS(10gr/100ml) applied 2 43, 2005.

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

6 extension of prostate cancer. Neither univariaten or multivariate

RISK FACTORS OF POSITIVE SURGICAL MARGINS analysis showed any statistical relationship between
AND BIOCHEMICAL RECURRENCE IN PATIENTS biochemical recurrence and any other risk factors covered in
TREATED WITH RADICAL PROSTATECTOMY this study. Discussion and Conclusion: There is wide
consensus that biochemical recurrence occurs in a large
Lucio Dell’ Atti, Gianni Ughi, Giovanni Pietro Daniele,
percentage of patients following successful RP. The
Gian Rosario Russo
biochemical recurrence was detected in 33% (93/282) of
Urologia Azienda Ospedaliero-Universitaria Arcispedale S. patients who had been treated with RP within 5 years, which
Anna, Ferrara, Italy indicates that the parameters related to the disease (positive
surgical margin, pathological T stage score and extension of
Introduction: Radical prostatectomy (RP) continues to be the prostate cancer) have a pivotal role in the PSA recurrence.
“gold standard” in the treatment of localized prostate cancer Thus, PSA recurrence appears to be related to the disease itself
for patients with a life expectancy of 10 years. However, rather than the surgery (RP).
biochemical recurrence may occur in 25 to 43% within ten
years after RP and additional treatment may be required in 1 Amling CL et al: Long-term hazard of progression after
35% of these patients. We investigated the factors (preoperative radical prostatectomy for clinically localized prostate cancer:
PSA, Gleason score, pathological T stage and extension of the continued risk of biochemical failure after 5 years. J Urol
tumor volume) more likely to influence biochemical recurrence 164: 101-105, 2000.
in men post-RP for organ confined prostate cancer. Patients 2 Kotb AF, Elabbady AA et al: Prognostic factors for the
and Methods: From January 2002 to December 2006 282 development of biochemical recurrence after radical
radical retropubic prostatectomies for localized prostate cancer prostatectomy. Prostate Cancer 2011:article ID: 485189,
were performed in patients of average age 65 years (52-74). 2011.
The operations were performed by two experienced surgeons 3 Chun FK, Briganti A et al: Surgical volume is related to the
in a single institution. Sixty-four patients were excluded from rate of positive surgical margins at radical prostatectomy in
the study due to positive lymph node metastases or lost follow- European patients. BJU Int 98: 1204-1209, 2006.
up. Following the EAU Guidelines on Prostate Cancer, the
follow-up was conducted 3.6 and 12 months post-RP during
the first year, and every six months in the second year and 7
thereafter with PSA level and digital rectal examination. None SERUM ISOFORM [-2]PROPSA (P2PSA) AND ITS
of the patients had adjuvant hormonal treatment and/or DERIVATES, %P2PSA AND PHI (PROSTATE
radiotherapy. PSA level >0.2 ng/ml by two subsequent HEALTH INDEX), ARE MORE ACCURATE THAN
measurements was defined as biochemical recurrence. To THE REFERENCE STANDARD TEST (PSA)
evaluate the incidence of biochemical progression we examined IN MEN SCHEDULED FOR REPEAT BIOPSY
these factors: percentage of positive surgical margins, the seat
Alessandro Larcher1, Massimo Lazzeri1,
of the margin, pathological stage (pT), pathological Gleason
Giovanni Lughezzani1, Giulio Gadda1, Alberto Abrate1,
score, maximum extension of prostate cancer (>15 mm) and
Vincenzo Scattoni1, Mattia Sangalli1, Luciano Nava2,
preoperative PSA. Results: The incidence of positive surgical
Vittorio Bin3, Tommaso Maga1, Piera Bellinzoni1,
margin was about 28% (79/282). With a median follow-up
Andrea Cestari1, Patrizio Rigatti1, Giorgio Guazzoni1
period of 5 years 31.6% (25/79) of the patients presented with
biochemical recurrence. The preoperative serum PSA 8.7 ng/ml 1Urologia Turro Università Vita-Salute, San Raffaele,
(3.4-16.2), average Gleason score (7.1±1.3), pathological T Milano, 2Urologia Fondazione Opera S. Camillo, Milano,
stage >=3 (11/25) and maximum extension of tumor >=15 mm 3Medicina Interna Università Di Perugia, Italy

(10/25). A univariate analysis showed that positive surgical

margin had a positive statistical association with pathological T Introduction: This study tests the hypothesis that [-2]proPSA
stage score (p=0,03), extension of prostate cancer (p=0.02) and (p2PSA) and its derivates, namely %p2PSA and PHI (prostate
biochemical recurrence (p=0.035). The most common location health index), are more accurate than reference standard tests
of a positive surgical margin was in the apex of the prostate, (tPSA, fPSA and %fPSA) in detecting PCa in men scheduled
which was about 58% (46/79). Sixty-seven percent (31/46) of for repeat biopsy. Patients and Methods: This study was an
patients with positive surgical margin in apex were also observational prospective evaluation of a cohort of men with
positive in the prostate lobe; other locations were prostate lobe one or two previous negative prostate biopsies, with persistent
30% (24/79), seminal vesicle 11% (9/79). The multivariate suspicion of PCa (suspected DRE, elevated tPSA and or low
analysis showed that positive surgical margin had a positive %fPSA) who were scheduled for repeat biopsy. Men receiving
statistical association with pathological T stage score and medical therapy known to affect serum PSA (dutasteride and

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

finasteride), suffering from prostatitis and having had invasive Background: The prostate health index (PHI) is a derivative of
treatment for benign prostatic hyperplasia (BPH), such as [-2]proPSA that showed a higher accuracy in predicting the
TURP or HoLEP, were excluded. Serum p2PSA, and its presence of prostate cancer (PCa) at initial biopsy in
derivates, namely %p2PSA {([-2]proPSA/10)/fPSA)} and comparison with established biomarkers. We developed and
Beckman Coulter PHI (prostate health index) {[[- internally validated a PHI-based nomogram for predicting the
2]proPSA/fPSA x squart PSA} were considered the index tests presence of PCa at initial biopsy. Patients and Methods: The
and compared with the reference standard tests (tPSA, fPSA study population consisted of a contemporary cohort of 434
and %fPSA). All the patients underwent ambulatory repeated patients with a total PSA <50 ng/mL who were referred to our
TRUS-guided prostate biopsies (1822 cores). The primary aim institution for an initial prostate biopsy. Outpatient transrectal
was to evaluate the accuracy of p2PSA and its derivates in ultrasound-guided prostate biopsies were performed according
detecting PCa. Results: From June 2010 and June 2011, 222 to a standardized institutional saturation scheme (18-22 cores).
men underwent repeated biopsy at our single high volume Logistic regression models were fitted to test the predictors of
centre. PCa cancer was found in 71/222 (31.9%) subjects. PCa at initial biopsy. Predictive accuracy estimates of biopsy
p2PSA, %p2PSA and PHI values were significantly higher outcome predictions were quantified using the area under the
(p<0.0001), and %fPSA values significantly lower (p<0.0001) receiver-operating characteristic curve (AUC). Differences in
in patients with PCa. At univariate accuracy analysis, %p2PSA AUCs were tested using the De Long method. Regression
(AUC: 72.5%) and PHI (AUC: 67.2%) were the most accurate coefficients were used to create a nomogram that was
predictors and significantly outperformed tPSA (AUC: internally validated using 200 bootstrap resamples. Finally, the
51.8%). %p2PSA significantly outperformed %fPSA (AUC: extent of overestimation or underestimation of the observed
60.2%) in the prediction of PCa (p≤0.001), but not PHI PCa rate at biopsy was determined with calibration plots.
(p=0.136). For %p2PSA a cut-off of 1.68 showed the best Results: Overall, 179 (41.2%) patients were diagnosed with
balance between sensitivity and specificity (respectively 67.6 PCa at initial extended prostate biopsy. In accuracy analyses,
and 66.9%; 95%C.I., 58.8-74.3). For PHI a cut-off of 40 PHI emerged as the most informative independent predictor
showed the best balance between sensitivity and specificity of PCa (AUC: 74.5%; p<0.001). The inclusion of PHI to a
(respectively 62 and 59.6%; 95%C.I., 51.3-67.5). At 90% of multivariable logistic regression model based on established
sensitivity, the cut-off of %p2PSA and PHI were respectively predictors of PCa (age and digital rectal examination)
1.23 and 28.8 with a specificity of 40.4 and 25.2%. At a significantly increased the predictive accuracy of a 3.4%
%p2PSA cut-off of 1.23, a total of 153 (68.9%) biopsies could extent (from 75.6 to 79.0%; p<0.001). Calibration of the
have been avoided; an overall of 6 PCa patients would have nomogram was good within the whole range of predicted
been missed but only 1 (5%) patient with a Gleason score of probabilities. Discussion and Conclusion: We developed a
7 or greater would have been missed. At a PHI cut-off of 28.8 nomogram based on PHI that can assist clinicians in the
a total of 116 (52.25%) biopsies could have been avoided; an decision to biopsy by giving patients an individual risk of PCa.
overall of 6 PCa patients would have been missed but no While internal validation provided evidence of good
patients with a Gleason score of 7 or greater would have been calibration and accuracy of the tool, external validation of our
missed. Discussion and Conclusion: %p2PSA and PHI are findings is still required.
more accurate than the reference standard tests (tPSA, fPSA
and %fPSA) in predicting repeat prostate biopsy outcome and
may be indicative of cancer aggressiveness. 9
RETZIUS SPARING ROBOT-ASSISTED
LAPAROSCOPIC PROSTATECTOMY:
8 INITIAL EXPERIENCE OF A CENTER
DEVELOPMENT AND INTERNAL VALIDATION WITH MORE THAN 200 ROBOTIC
OF A PROSTATE HEALTH INDEX (PHI) BASED NERVE SPARING PROSTATECTOMIES
NOMOGRAM FOR PREDICTING PROSTATE
Roberto Nucciotti1, Francesco Mengoni2, Fabrizio Viggiani2,
CANCER AT INITIAL EXTENDED BIOPSY
Fabio Massimo Costantini2, Alessandro Bragaglia2,
Giovanni Lughezzani, Alessandro Larcher, Alberto Abrate, Giandomenico Passavanti2, Michele Gnech2, Valerio Pizzuti2
Giuliana Lista, Mattia Sangalli, Fabio Fabbri, 1U.O. Urologia Scuola di Chirurgia Mininvasiva e Robotica
Tommaso Maga, Nicolò Maria Buffi,
Ospedale Della Misericordia, Grosseto;
Firas Abdollah, Andrea Losa, Andrea Cestari, 2U.O. Urologia Ospedale della Misericordia, Grosseto, Italy
Massimo Lazzeri, Giorgio Guazzoni
Urologia Turro Università Vita-Salute, San Raffaele, Milano, Purpose: The Retzius sparing approach for Robot-assisted
Italy laparoscopic prostatectomy (RALP) passes through the

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

Douglas space, following a completely intrafascial plane - December 31, 2010 and findings were categorized into
without any dissection of the anterior compartment, which carcinoma (PCa), benign, PIN and ASAP. The mean age of
contains neurovascular bundles, Aphrodite’s veil, endopelvic patients was 66 years and mean number of biopsied fragments
fascia, the Santorini plexus, pubourethral ligaments, and all of was 12. We investigated repeated prostate biopsies in patients
the structures thought to play a role in maintenance of who had been diagnosed with PIN and ASAP. The second
continence and potency. After seeing the Retzius sparing biopsy was carried out about 4 months after diagnosis of
technique developed by Prof. Bocciardi, we realized the great ASAP and 6 months after diagnosis of high grade PIN. All
potential of this approach that respects, like no other, the patients diagnosed with HGPIN or ASAP on second biopsy
anatomical relationships. Patients and Methods: From were subjected to a third transrectal biopsy. Results: Of 1018
September 2011 to December 2011 we performed seven prostate biopsies, ASAP was diagnosed in 38 (3.7%) patients
robotic radical prostatectomies with the Retzius sparing [Group A, HGPIN in 56 (18%) [Group B] and HGPIN +
approach. The average age of patients was 54 years (45-59 ASAP in 17 (1.7%) [Group C]. All three groups of patients
years), the mean PSA 7.4 ng/ml (4.2-8.3 ng/ml), Gleason (n:111) underwent a second transrectal prostate biopsy. The
score <7.% Ca/core <30%, the mean volume was 48 ml (38- histopathological findings of the second biopsy in the three
54 ml). Results: After removal of the catheter in the fifth day groups of patients were: Group A: PCa 23.6% (9/38), HGPIN
we had 3 urinary retentions, then the catheter was repositioned 18.4% (7/38), ASAP 5.2% (2/38); Group B: PCa 17.8%
and removed the tenth day. In the other 4 cases after removing (10/56), HGPIN 25% (14/56), ASAP 5.3% (3/56); Group C:
the catheter in the fifth day, the patients were continent PCa 64.7% (11/17), HGPIN 11.7% (2/17), ASAP 23.5%
without the need to use pads, mean blood loss was 270 ml (4/17). Patients who still had a second biopsy with the
(150-340), the average surgical time was 150 min. (125-170 diagnosis of HGPIN or ASAP were subjected after about 6
min), and no procedure was converted to another technical months to a third transrectal biopsy with a mean number of
approach. Conclusion: The technique is easily reproducible 16 biopsies. In Group A: 40% (4/10), in Group B: 17.6%
for a urologist who has experience in nerve sparing RALP. (3/17) and in Group C: % 16.6 (1/6) of the patients had a
With this technique it is not necessary to dissect the seminal diagnosis of prostate cancer at the third biopsy. The positivity
vesicles to increase the operating space, and the respect of rates of the second and third biopsy are 27% (30/111) and
anatomical structures and anatomical relationship is absolute. 25% (8/32) respectively. 21% (8 of 38) of cancers are
Functional results are promising, and we think that this is the diagnosed at the third biopsy. The incidence of HGPIN was
best technique for the treatment of low-risk prostate cancer 18%, ASAP 3,7% and HGPIN plus ASAP was identified in
(D’Amico risk classification). 1,7% of 1018 biopsies analyzed. There was no difference
between groups where cancer was or was not diagnosed on
repeated biopsy in relation to age and serum PSA levels.
10 Conclusion: Data presented are important because they derive
RE-BIOPSY OF PROSTATE AFTER DIAGNOSIS OF from a reference urology department which conducts a large
PROSTATIC INTRAEPITHELIAL NEOPLASIA AND number of biopsy analyses every year, and can be seen as an
ATYPICAL SMALL GLAND PROLIFERATION indicator of management adopted by the urologist when facing
a diagnosis of PIN and ASAP. The numbers we found are also
Lucio Dell’ Atti1, Giovanni Pietro Daniele1, Consuelo Ricci2,
important since they are based on extended biopsies rather
Gianni Ughi1, Gian Rosario Russo1
than restricted to sextants where the mean number of
1Urologia Azienda Ospedaliero-Universitaria Arcispedale S. fragments was 12, including biopsies that can be regarded as
Anna, Ferrara; presenting saturation with 24 fragments. Although in literature
2Istituto di Chirurgia Generale Arcispedale “S. Anna”, there are conflicting experiences about the manner and
Ferrara, Italy frequency of re-biopsy after a diagnosis of HGPIN or ASAP,
in our experience the diagnosis that most frequently led to
Introduction: Isolated high grade prostatic intraepithelial repeated biopsy was HGPIN + ASAP. Prostate cancer was
(HGPIN) and/or atypical small acinar proliferation (ASAP) on most often diagnosed after the initial diagnosis of ASAP. In
prostate biopsy increases the risk of identifying cancer on addition, our results suggest that patients with a diagnosis of
repeat biopsy. The aim of this study was to assess the HGPIN or ASAP in two consecutive biopsies should be
incidence of diagnosis of HGPIN and ASAP at urology subjected to a third biopsy.
reference center. We report the results of repeated prostate
biopsy for HGPIN and/or ASAP, and propose an optimal 1 Pascual Mateo C, Lujan Galan M et al: Clinical significance
evaluation of the indexes and findings on repeated biopsies. of prostatic intraepithelial neoplasm and atypical small
Patients and Methods: We reviewed the reports from 1018 acinar proliferation: relationship with prostate cancer. Actas
prostate biopsies that had been analyzed between July 1, 2007 Urol Rsp 32(7): 680-685, 2008.

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

2 Leite K, Cristina A et al: Repeat prostate biopsies following compared with ΔΔ those of normal tissue as fold increase
diagnoses of prostate intraepithelial neoplasia and atypical calculated by 2-Ct method (3). Results: By real time RT-PCR
small gland proliferation. Int Braz J Urol 31(2): 131-136, analysis of indicated miRs, only the miR-501 was found
2005. differentially expressed in kidney carcinomas compared with
3 Borboroglu PG, Sur RL et al: Repeat biopsy strategy in normal renal tissues. In particular miR-501 expression was
patients with atypical small acinar proliferation or high 5.35 fold increased in ccRCC with respect to normal tissues.
grade prostatic intraepithelial neoplasia on initial prostate Conversely, in pRCC this miR was found 2.56 fold decreased
needle biopsy. J Urol 166(3): 866-870, 2001. compared with normal kidney. Because, the expression levels
of miR-501 in ccRCC showed a extremely variable
distribution, this miR may not be used as a marker for ccRCC.
11 Moreover, no correlation between miR-501 expression and
ROLE OF THE MIR-501 IN RENAL CARCINOMAS tumor grading was observed. However, the low expression of
miR-501 in ccRCC as well as in pRCC samples correlated
Alessandra Mangolini1, Lucio Dell’ Atti2, Anna Bonon1,
with a good prognosis, thus the downregulation of miR501
Maurizio Simone3, Eros Magri4, Patrizia Querzoli4,
could be considered as a marker for positive prognosis in
Massimo Pedriali4, Gian Rosario Russo2,
ccRCC and pRCC kidney carcinomas. Conclusion: Our results
Laura Del Senno1, Gianluca Aguiari1
demonstrate that in renal carcinomas the miR-501 was
1Dipartimento di Biochimica e Biologia Molecolare significantly over-expressed in ccRCC, while was down-
Università Degli Studi Di Ferrara; regulated in pRCC. High levels of miR-501 are not related
2U.O. Urologia Arcispedale “S. Anna”, Ferrara; with grading and metastasis in ccRCC, however, when it is
3U.O. Urologia Ospedale Del Delta, Lagosanto; down-regulated could promote a good prognosis.
4Dipartimento di Medicina Sperimentale e Diagnostica

Università Di Ferrara, Italy 1 Di Leva G and Croce CM: Roles of small RNAs in tumor
formation. Trends Mol Med 16(6): 257-67, 2010. Review.
Background: MicroRNAs (miR) are small, noncoding RNAs 2 Juan D, Alexe G, Antes T, Liu H, Madabhushi A, Delisi C,
that regulate gene expression. In particular, miRs are involved Ganesan S, Bhanot G and Liou LS: Identification of a
in many biological processes, including differentiation, microRNA panel for clear-cell kidney cancer. Urology
proliferation and cell death. In addition to their physiological 75(4): 83541, 2010.
functions, miRs are found to be aberrantly expressed in many 3 Aguiari G, Banzi M, Gessi S, Cai Y, Zeggio E, Manzati E,
carcinomas including renal tumors and to play oncogenic or Piva R, Lambertini E, Ferrari L, Peters DJ, Lanza F, Harris
tumor suppressive roles in cancer cells (1-2). Because, we PC, Borea PA, Somlo S and Del Senno L: Deficiency of
have observed by microarray analysis that some miRs (miR polycystin-2 reduces Ca2+ channel activity and cell
142-5p, 601, 362, 196b, 202 and 501) were differentially proliferation in ADPKD lymphoblastoid cells. FASEB J
expressed in autosomal dominant polycystic kidney disease 18(7): 884-886, 2004.
(ADPKD) which is an hyperproliferative disease, we have
analyzed the expression of these miRs in kidney carcinomas
to better understand their role in renal tumorigenesis. In 12
particular, we have studied the most common renal neoplasms METANEPHRIC ADENOMA OF THE KIDNEY:
as clear cell (ccRCC), papillary (pRCC), chromophobe STUDY OF EIGHT PATIENTS
(chRCC), with respect to normal kidney tissues. Materials and
G. Saraceni, F. Mengoni, E. Brunocilla, R. Schiavina,
Methods: We selected and analyzed 39 post-nephrectomy
M. Garofalo, B. Corti, G.C. Rocca,
fresh frozen tissues (including 23 neoplastic samples: 14
Z. Zukerman, G. Severini, G. Martorana
ccRCC, 6 pRCC, 3 chRCC), and 13 paraffin-embedded
tumors samples (7 ccRCC, 4 pRCC, 2 chRCC) with matched Department of Urology, Pathology Unit, Department of
normal tissues. Total RNA was extracted with TRIZOL (fresh Haematology, Oncology and Laboratory Medicine,
frozen tissues) or the RecoverAll® Total Nucleic Acid Isolation S. Orsola-Malpighi Hospital,University of Bologna,
kit (paraffin-embedded tissues). Microarray analysis was Bologna, Italy
performed in normal kidney and ADPKD cell lines following
the manufacturer’s protocols of microarray facility (Lab of Dr. Background: Metanephric adenoma is a rare benign tumor of
Negrini, University of Ferrara). Quantitative real time PCR for the kidney. First descriptions of metanephric adenoma (MA)
mature miRs was performed with TaqMan method. was by Page and Granier in the French literature in 1979.
MicroRNA levels were expressed as ΔΔCt relative to reference Polycythemia is frequently associated with metanephtic
gene U6 snRNA. MiR RNA levels in tumor sample were adenoma, and often it might be possible to suspect the

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

diagnosis of this neoplasia. The differential diagnosis of MA is performed. Descriptive statistics were adopted. The median
essentially that of two lesions: the solid variant of PRCC and PFS and OS were estimated using the Kaplan-Meier method.
epithelial-predominant Wilms tumor. Methods: From the Hazard Ratios (HR) for PFS/OS and the 95% confidence
beginning of 2000 till the end of 2011, we identified eight intervals (CI) were derived by using the Cox univariate model.
male patients with metanephric adenoma in our hospital, from A multivariate Cox proportional hazard model was developed.
which only two patients were previously selected to be Results: 65 pts were included; patients’ baseline characteristics:
operated for this tumor, whereas the other six underwent male/female: 67.7%/32.3%; radical nephrectomy yes/no:
surgery for a different condition and the pathological findings 84.6%/15.3%; Fuhrman Grading 1/2/3/4: 1.5%/15.4%/38.5%/
showed a metanephric adenoma. Results: All patients are in 18.5%; MSKCC Score favorable/intermediate/poor:
good clinical condition except two who died because of other 21.5%/55.4%/12.3%; treatment SU/SO/SU-SO: 46.2%/26.2%/
diseases. The mean (range 0.5-4.1 cm) dimension was about 2 27.7%; >1 metastatic site yes/no: 29.2%/70.8%. Objective
cm. Methanephric adenoma is solid, and may have areas of response (HR 6.69, 95% CI 3.03-14.78, p<0.0001) and
hemorrhage, necrosis and/or cystic degeneration. Surgical MSKCC score (HR 3.21, 95% CI 1.38-7.46, p=0.007) were
excision of the tumor is considered the treatment of choice. independent significant preditors for PFS at the multivariate
Conclusion: The metanephric adenoma is a benign condition. analysis. Log-rank analysis is shown in the table:
Diagnosis by computerized tomography and percutaneous
biopsy and treatment by nephron sparing surgery are PFS OS
reccomended.
Median p 1-yr Median p 1-yr
(95% CI) (%) (95% CI) (%)

13 Response
PREDICITIVE FACTORS OF PROGRESSION FREE Yes 16 (13-19) <0.0001 77.6 n.r. 0.0009 94.7
SURVIVAL (PFS) AND OVERALL SURVIVAL (OS) IN No 4 (3-6) 15.4 10 (8-12) 40.4
ADVANCED RENAL CELL CARCINOMA (A-RCC) MSKCC score
PATIENTS TREATED WITH TYROSINE KINASE Favourable 18 (3-34) 0.06 62.9 n.r. 0.04 100
Intermediate 6 (4-9) 33.3 14 (4-23) 53.4
INHIBITORS (TKIs): A RETROSPECTIVE ANALYSIS
Poor 3 (0-6) 14.3 11 (2-18) 47.6
OF A MONO-INSTITUTIONAL SERIES Treatment
Francesco Massari1, Francesca La Russa1, Francesca SU 9 (3-14) 0.34 41.2 29 (5-52) 0.20 60.7
SO 6 (1-11) 36.5 15 (4-25) 57.1
Maines1, Emilio Bria1, Isabella Sperduti2, Matteo Brunelli3,
SU-SO 7 (5-8) 36.4 n.r. 71.1
Teodoro Sava4, Annamaria Molino4, Walter Artibani5,
Guido Martignoni3, Giampaolo Tortora1
Conclusion: Despite the limitations of a retrospective study,
1Oncologia Medica DU Azienda Ospedaliera Universitaria our data confirm the value of MSKCC risk score and suggest
Integrata (AOUI), Verona; that response may represent an independent predictor for PFS.
2Direzione Scientifica Regina Elena National Cancer Because of the small power, no differences according to
Institute, Roma; treatment (SU, SO or SU-SO) emerged; therefore, results of
3Anatomia Patologica Azienda Ospedaliera Universitaria comparative prospective trials, able to elucidate the optimal
Integrata (AOUI), Verona; sequence of targeted agents, are strongly awaited.
4Oncologia Medica DO Azienda Ospedaliera Universitaria

Integrata (AOUI), Verona;

5Urologia Azienda Ospedaliera Universitaria Integrata 14
(AOUI), Verona, Italy EFFECTS OF DUAL PI3K AND mTOR INHIBITION
ON INCIDENCE AND LOCAL GROWTH OF
Background: The introduction of targeted therapy has PROSTATE CANCER BONE METASTASES
significanlty contributed to change in the prognosis of A-RCC’s
Giovanni Luca Gravina1, Andrea Mancini2, Nadia Rucci3,
patients (pts). Nevertheless, both the optimal strategy to
Chris Liang4, Mattia Capulli3, Jay Gibbons4, Carla Tatone5,
administer these agents and which predictive factor is able to
Anna Maria Teti3, Andrea Lenzi6, Emmanuele A. Jannini7,
identify the appropriate treatment are still controversial. The
Claudio Festuccia8
aim of this analysis was to screen for predictors of outcome in
the context of a retrospective mono-institutional series. 1Dipartimento Di Medicina Sperimentale, Università Di
Methods: A retrospective analysis including A-RCC pts treated L’Aquila Divisione Di Radioterapia;
with Sunitinib (SU), Sorafenib (SO), or pre-planned sequential 2Dipartimento Di Scienze e Tecnologie Biomediche,

SU-SO at AOUI between January 2005 and April 2011 was Università Di L’aquila Biochimica;

1854
 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

3Dipartimento Di Medicina Sperimentale, Università Di impairment), score 4 (Xray visible lesions with cortical
L’aquila Bone Pathology, Italy; impairment with/without fractures) and score 5 (extended
4Xcover Llc, West Palm Beach, Fl Translational Oncology osteolysis with extra-tibial growth). X480 was able to
Research, U.S.A.; significantly reduce tumor burden (4/20 tibiae with score >3)
5Dipartimento Di Scienze Delle Salute, Università Di relative to those observed in untreated animals (12/20 tibiae
L’aquila Biologia Cellulare; with score >3, p<0.05). Although mTor selective inhibition by
6Dipartimento Di Medicina Sperimentale, Università La X414 was able to reduce tumor burden (7/20 tibiae with score
Sapienza Di Roma Fisiopatologia; >3), this was not significant. However, histo-morphometric
7Dipartimento Di Medicina Sperimentale, Università Di analyses revealed that X414 treated animals showed
L’aquila School of Sexology; significant reduction of tumor mass (p<0.05). These findings
8Dipartimento Di Medicina Sperimentale, Università Di provide the rationale for including PI3K/Akt/mTOR kinase
L’aquila Radiobiology, Italy inhibitors as part of the therapeutic regimen for PCa patients
and suggest that dual inhibition of PI3K and mTor may more
Although phosphoinositide 3-kinase PI3K activation is effectively inhibit metastasis and tumor host interaction in the
associated to prostate cancer (PCa) progression, the bone microenvironment than inhibition of mTor alone.
contribution of mTOR and its interaction partners toward
regulating PCa progression and metastasis remains poorly
understood. The main aims of this report are: (I) to verify if 15
the inhibition of PI3K/Akt/mTOR pathway by using the dual EFFECTS OF 1D11 AN ANTIBODY AGAINST
PI3K/mTOR kinase inhibitor, X480, was able to modulate cell TRANSFORMING GROWTH FACTOR BETA
proliferation and apoptosis in prostate cancer cells; (II) to (TGF-Β) ON INCIDENCE AND LOCAL GROWTH
compare the effects of X480 with the mTOR inhibitor, X414; OF PROSTATE CANCER BONE METASTASES
(III) to verify the effects of these drugs on the production of
Giovanni Luca Gravina1, Andrea Mancini2, Nadia Rucci3,
proteases involved in cell migration and metastases and (IV)
Mattia Capulli3, Scott Lonning4, Anna Maria D’alessandro5,
the final endpoint of this study is to examine the role of
Anna Maria Teti3, Andrea Lenzi6, Emmanuele A Jannini7,
PI3K/AKT/mTOR inhibition in the incidence of bone
Claudio Festuccia8
metastases as well as its role on the growth of tumor cells in
the bone microenvironment. We analyzed the cytotoxic effects 1Dipartimento Di Medicina Sperimentale, Università Di
and biochemical arrangement induced by these compounds by L’Aquila Divisione Di Radioterapia;
using two nontumor prostate epithelial cell lines and a series 2Dipartimento Di Scienze e Tecnologie Biomediche,

of 8 prostate cancer cell lines and 11 prostate cancer cell Università Di L’aquila Biochimica;
derivatives. In vivo, male nude mice were injected with 3Dipartimento Di Medicina Sperimentale, Università Di

PC3cells by intracardiac (metastatic model) and intratibial L’aquila Bone Pathology, Italy;
(local growth) method. Dual inhibition of PI3K/mTOR 4Department of Oncology Research, Genzyme Corporation.

signaling, using X480 attenuated cell proliferation and induced Framingham, Ma Traslational Oncology Research, U.S.A.;
apoptosis in prostate cancer cells. The effects were more 5Dipartimento Di Scienze Delle Salute, Università Di

marked in presence of a PTEN loss and Akt activation (by L’aquila Biochimica;
increased EGFR/Her2 activity or PIK3CA mutation). mTor 6Dipartimento Di Medicina Sperimentale, Università La

inhibition by X414 was also able to reduce cell proliferation Sapienza Di Roma Sezione Di Fisiopatologia;
and to induce apoptosis. Cell migration and invasion 7Dipartimento Di Medicina Sperimentale, Università Di

experiments indicated that the inhibition of the PI3K/mTor L’aquila School of Sexology;
pathway was associatedwith marked reduction of metastatic 8Dipartimento Di Medicina Sperimentale, Università Di

potential. The analyses of in vivo experiments revealed a L’aquila Radiobiology Laboratory, Italy
significant reduction of metastases incidence and tumor
burden after treatment with X480 (p<0.05). Evaluation of Transforming growth factor beta (TGFβ) plays an important
tumor growth in bones after intratibial injection revealed a role in prostate cancer (PCa) development and this growth
significant reduction both after X480 and X414 treatments. factor has been implicated in the pathogenesis of PCa-derived
Tibiae obtained 35 daysafter intratibial injection of nude mice bone metastases. The main aims of this report are: to verify if
wereanalyzed by Xray and microCT and scored as: score 0 the inhibition of TGFβ pathway, by using the pan-neutralizing
(absence of tumor growth after xRay and microCT analyses), anti-TGF-β antibody (1D11), was able to modulate cell
score 1 (osteolytic lesions visible only to microCT analyses proliferation and apoptosis in prostate cancer cells and to
and <5 mm2), score 2 (lesions visible only microCT and >5 examine the role TGFβ inhibition in the incidence of bone
mm2), score 3 (lesions visible to xRay without cortical metastases as well as its role on the growth of tumor cells in

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

the bone microenvironment. 1D11 is a murine monoclonal 3Dipartimento Di Medicina Sperimentale, Università Di
antibody against all three TGFβ isoforms and has been used as L’aquila Radioterapia Oncologica;
a surrogate for a fully human antibody (GC1008) currently in 4Dipartimento Di Medicina Sperimentale, Università Di

clinical development. We analyzed the effect of 1D11 on the L’aquila Oncologia Medica;
growth of C4-2B and PC-3 bone derived PCa cells in vitro by 5Karyopharm Therapeutics, Newton, Ma, USA Research and

measuring radiolabeled thymidine incorporation into DNA as Development, U.S.A.;

well as the biochemical arrangement induced by treatmnent. 6Dipartimento Di Medicina Sperimentale, Università Di

In vivo, male nude mice were injected with PC3cells by L’aquila Radiobiology Laboratory, Italy
intracardiac (metastatic model) and intratibial (local growth)
method. We monitored the tumor burden and bone responses CRM1 (Xpo1) is a key nuclear export protein which
in vehicle control, 1D11 and 13C4 (isotype control antibody) controls the nuclear export of multiple tumor suppressor
treated mice. PC3 and C4-2B cells are TGF-β1 responsive and proteins (TSP) and cell proliferation pathways including
have an intact constitutive TGF-β signal transduction pathway p53, p21, FOXO, PI3K/AKT, Wnt/β-catenin and NF-κB.
as confirmed by pSmad2 induction and growth inhibition Mislocalization of TSP can abrogate their functions as well
when stimulated with TGF-β1. As expected, 1D11 but not as render chemotherapies ineffective. Induction of nuclear
13C4, inhibited the TGF-β1-induced pathway activation and expression of TSP and chemotherapy targets, by CRM1
growth inhibition of PC-3 and C4-2B cells. The analyses of in inhibition can restore their tumor suppressor functions and
vivo experiments revealed a significant reduction of metastases increase drug sensitivity. We have developed orally active,
incidence and tumor burden after treatment with 1D11 small molecule SINE that irreversibly and potently inhibit
(p<0.05) with significant less bone loss due to reduced CRM1 mediated nuclear export of multiple TSP and other
osteoclast activity in PC-3 tumor-bearing bones than in the cargoes (IC50 <100 nM). Here, we describe in vitro results
untreated mice. Tibiae obtained 35 days after intratibial using SINE compounds, KPT-185 in vitro and KPT-251 in
injection of nude mice were analyzed by Xray and microCT vitro and in vivo on seven prostate cancer (PrCa) cell lines
and scored as: score 0 (absence of tumor growth after xRay representing distinct differentiation/progression states of
and microCT analyses), score 1 (osteolytic lesions visible only disease and genotypes: LAPC-4 (Androgen receptor [AR]
to microCT analyses and <5 mm2), score 2 (lesions visible positive, androgen dependent with low Akt/mTOR activities,
only microCT and >5 mm2), score 3 (lesions visible to xRay p53 wt); LnCaP (AR positive, androgen dependent with
without cortical impairment), score 4 (Xray visible lesions high Akt/mTOR activities, p53 wt); LnCaP-C81 and LnCaP-
with cortical impairment with/without fractures) and score 5 C4-2B (AR positive, androgen independent with high
(extended osteolysis with extra-tibial growth). 1D11 was able Akt/mTOR activities, p53 wt); 22rv1 (AR positive,
to significantly reduce tumor burden (6/20 tibiae with score androgen independent with low Akt/mTOR activities, p53
>3) relative to those observed in untreated animals (14/20 wt); PC3 (AR negative, with high Akt/mTOR activites and
tibiae with score >3, p<0.05). In summary, we report for the no p53 function (p53 del) and DU145 (AR negative, with
first time that TGF-β neutralization with a monoclonal low Akt/mTOR activites and mutant p53). Benign prostatic
antibody (1D11) can control PCa bone metastases and may be hyperplasia line (BPH1) and Prostatic epithelial line (EPN)
a useful therapeutic approach in men with advance PCa. were used as non-neoplastic controls. We show that SINE
block CRM1 mediated nuclear export of FOXO and p53
with a IC50 values <100 nM in both PrCa and non-neoplastic
16 cell lines. KPT compounds are selectively cytotoxic to PrCa
SELECTIVE INHIBITORS OF NUCLEAR lines with EC50s between 10 and 1000 nM, and show
EXPORT (SINE) ACTIVATE MULTIPLE limited cytotoxicity on the nonneoplastic EPN and BPH1
TUMOR SUPPRESSOR PATHWAYS AND lines (EC50 >5-20 SINE cytotoxic effects are independent of
KILL PROSTATE CANCER CELLS ACROSS p53 status, and induce caspase-3 activation. SINE display
MULTIPLE GENOTYPES IN VITRO AND IN VIVO synergistic effects in combination with cisplatin and
docetaxel in vitro with combination indices between 0.3 and
Giovanni Luca Gravina1, Andrea Mancini2, Francesco
0.8. In vivo results indicate that KPT-251 show a dose-
Marampon3, Enrico Ricevuto4, Sharon Shechter5, Vincent
dependent inhibition of tumor growth. KPT251 was also
Sandanayaka5, Michael Kauffman5, Sharon Shacham5,
additive when administered at 30 mg/kg/5 days/week per os
Claudio Festuccia6
with docetaxel and cisplatin by using the aggressive p53 wt
1Dipartimento Di Medicina Sperimentale, Università Di 22rv1 xenografts. Taken together, CRM1 inhibition
L’Aquila Divisione Di Radioterapia; represents a completely novel, neoplasia-selective and well
2Dipartimento Di Scienze E Tecnologie Biomediche, tolerated target for use as single agent or in combination
Università Di L’aquila Biochimica; with chemotherapy for PrCa.

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

17
PROGNOSTIC FACTORS OF KIDNEY
TUMORS IN T3 STAGE: ROLE OF
PERIRENAL FAT INFILTRATION, RENAL
SINUS INFILTRATION AND VENOUS THROMBOSIS
G.C. Rocca, R. Schiavina, E. Brunocilla, M. Garofalo, A.
Bertaccini, S. Concetti, G. Saraceni, F. Chessa, A. Baccos, Z.
Zukerman, C.V. Pultrone, G. Passaretti, M.S. Rossi, D.
Romagnoli, G. Martorana
Department of Urology, S. Orsola-Malpighi Hospital,
University of Bologna, Bologna, Italy

Introduction: The outcome predictors for renal cell cancer

(RCC) remains controversial; although many parameters have
been tested for prognostic significance, only a few have
achieved widespread acceptance in clinical practice. The
prognostic significance of perirenal fat or sinus infiltration,
and venous tumor thrombus extension in patients with renal
cell carcinoma (RCC) is a matter of many controversies in the
current literature. Patients and Methods: We analyzed the
pathological finding and clinical follow-up of 593 patients
who underwent radical nephrectomy for RCC from 2000 to
2011 at our institution. The mean age was 63.9±11.8, the two pathological characteristics could better identify those
mean tumor size was 7.39 cm ± 2.73 cm. Among these we patients at higher risk of recurrence. Tumor size, Furhman
selected 125 patients with T3 stage at pathological evaluation grading, presence of distant metastases and vein trombosis are
and grouped them as follows: group A (63 patients) with independent prognostic factors in pT3. Large prospective
invasion of peritumoral fat and/or hilar fat, group B (19 series are needed to validate these findings.
patients) with renal vein trombosis or vena cava trombosis,
group C (43 patients) with both venous trombosis and the
peritumoral and/or hilar fat invasion. We evaluated the cancer 19
specific survival (CSS) between the three groups using Kaplan NON INVASIVE DETECTION OF BLADDER
Meier survival curves for the univariate analysis and Cox CANCER BY ELECTROMAGNETIC INTERACTION
regression model for multivariate analysis. Results: The mean
Francesco Esperto1, Christof Kastner2
follow-up was 41.44 months (±35.27, range 1-140 months),
the median survival was 31 months. 98 patients underwent 1Urologia Azienda Ospedaliera Sant’Andrea, Italy;
lymphadenectomy. The histological subtypes of our group 2Dept. of Urology, Cambridge, Addenbrookes Hospital, U.K.
were: clear cell carcinoma 102 (79.4%), papillary 17(14%),
cromophobe 4(2.9%), NAS 2(3.7%); The Furhman Grading Introduction: Biological tissues interact with EM waves.
was: G2 32(25.9%), G3 69(54.1%), G4 24(20%); lymph node Cancer behave differently to benign tissue in an EM field using
involvement was noted in 19 (16.4%) and distant metastases in the phenomena of non linear resonance. The objective of this
18 (16%). At univariate analysis, there was a significantly study was to evaluate the diagnostic accuracy of bladder cancer
difference in CSS among the three groups (Figure 1, detection using the TRIMprob, a nonlinear tunable oscillator
p=0.036). However group A had a significantly higher survival generating extremely low energy multiple electromagnetic
than group C (p=0.008) but not than group B (p=0.364) fields, that has been evaluated for the detection of several
because of the small number of cases in the group B. At human cancers in clinical and experimental studies (1-3).
multivariate logistic regression analysis, the new grouping was Patients and Methods: 200 consecutive patients referred to
not an independent prognostic factor, while tumor size, Sant’Andrea’s outpatients clinic for urethrocystoscopy were
grading and distant metastases were independent prognostic enrolled in the study. All patients were investigated by history,
factors. Conclusion: The current TNM staging system for physical examination, urinalysis, urine culture and urine
RCC does not account for the simultaneous presence of cytology, urethrocystoscopy and TRIMprob test. Transurethral
perirenal fat and vein trombosis as a distinct category in the resection of the bladder was performed in case of any
pT3. A new subgroup with the simultaneous presence of the suspicious lesion. Main indications for cystoscopy were gross

1857
 ANTICANCER RESEARCH 32: 1843-1966 (2012)

from January 2008 to October 2010. It was considered positive

when the signal at 465 MHz was set to 0 level. Nonlinear
resonance was analyzed at 465, 930 and 1395 MHz. Results:
Analysis of resonance values at 465MHz showed a statistically
significant difference between patients with and without
bladder cancer (p<0.0001 at Mann Whitney test). No
statistically significant difference was observed in the values at
930 (p<0.073) and 1395 MHz (p<0.327). The following
accuracy values were observed for the diagnosis of bladder
cancer: sensitivity, 86%; specificity, 94%; positive and negative
predictive value of 86% and 94% overall, diagnostic accuracy
was 92%. No significant difference was found between the two
different positions and operators. No correlation was seen
between TRIMprob test and tumor size and/or grade.
*p<0.0001 at Mann Whitney test
**p<0.073 at Mann Whitney test Discussion and Conclusion: In our experience the TRIMprob
***p<0.327 at Mann Whitney test has a high diagnostic accuracy for the detection of bladder
cancer in patients undergoing urethrocystoscopy for
Figure 1. Comparison between the mean signal intensity in the three haematuria and after-TURB follow-up. Confirmation clinical
spectral lines (465, 935 and 1395 MHz) of the TRIMprob test in and experimental studies are currently ongoing to better define
patients with positive and negative urethrocystoscopy for the the possible clinical role of the TRIMprob for the management
presence of neoplasms.
of patients at risk of bladder cancer.

1 Bellerofonte C, Vedruccio C, Tombolini P, Ruoppolo M and

Tubaro A: Non-invasive detection of prostate cancer by
haematuria and follow-up of patients after TURB. Patients electromagnetic interaction. Eur Urol 47: 29-37, 2005.
affected by pelvic tumors, urinary tract infection, cardiac 2 Gervino G, Autino E, Kolomoets E, Leucci G and Balma M:
pacemakers or with other electromagnetic devices were Diagnosis of bladder cancer at 465 MHz. Electromagn Biol
excluded from the study. The TRIMprob was moved over the Med 26(2): 119-134, 2007.
surface of the patient’s pubic region while standing in front of 3 Tubaro A, De Nunzio C, Trucchi A, Stoppacciaro A and
the system receiver in two different positions, with a bladder Miano L: The electromagnetic detection of prostate cancer:
filling of 150 ml after endoscopic examination. Two operators evaluation of diagnostic accuracy. Urology 72(2): 340-344,
blinded to the patient status independently conducted the test 2008.

Figure 2. Flowchart of patients undergoing cystoscopy. Patients with a significant decrease of the electro-magnetic signal at 465MHz were
labelled as “ positive at TRIMprob test “ and those without any significant decrease were described as “negative at TRIMprob test”.

1858
 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

20 as a growth factor towards the tumor (2), but also determines

THE USE OF UCYT+ ALLOWS TO ANTICIPATE a positive effect on the reduction of sanitary costs. The uCyt+
DIAGNOSIS OF UROTHELIAL CARCINOMA (UC) method, easily performed, detects minimum quantities of
neoplastic antigens much earlier than morphological
Amelia Bernardi1, Ester Berardengo1, Fabrizio Fop2,
modifications visualized through traditional cytology. For
Margherita Gussio1, Patrizia Lovadina1, Giuliana Maffei1,
example, a Borderline Positivity, also referred to one single
Francesco Morabito3
positive cell located in the sample can help in the diagnosis of
1Anatomia Patologica Ospedale San Giovanni A.S. the neoplasia when it develops and/or to precauciously
Aou Molinette; visualize relapses. According to our results, a positive uCyt+
2Nefrologia Dialisi e Trapianto Aou Molinette Torino; test in the presence of a negative cytology exam should not be
3U.O. Urologia Ospedale Cardinal Massaia Asti, Italy underestimated. In fact, in 50 patients, that normally would
have been controlled with longer frequency intervals, a more
Introduction: The aim of this retrospective study was to accurate surveillance interval with contemporary urinary
evaluate over a six-year period, if the use of the uCyt+ test cytology and uCyt+ exams, diagnosed the neoplasia and/or the
along with the cytology examination of spontaneous urine relapse, even when the lesion was very small (<1 cm).
samples would detect, as affirmed in literature (1), the
presence of neoplasic cells, not revealed by cytology alone. 1 Têtu B, Tiguert R, Harel F and Fradet Y: ImmunoCyt/u
Therefore, anticipating diagnosis months ahead with respect Cyt+TM improves the sensitivity of urine cytology in
to the cystoscopy examination. Patients and Methods: The patients followed for urothelial carcinoma. Modern
patients had previously given their informed consent that the Pathology 18: 83-89, 2005.
voided urine sample would be processed separately for the 2 Oosterlinck W: Recent clinical trials in superficial bladder
standard staining in routine cytology (Papanicolaou technique) cancer. Current Opinion in Urology 11(5): 511-515, 2001.
and then for the FDA approved immunofluorescent uCyt+ test
developed by Fradet and Lochart in 1997. The urine samples
were tested with uCyt+ and the slides were read under a 21
fluorescent microscope at a 40x magnification according to MINIMALLY INVASIVE INTRACORPOREAL
manufacturer instructions. A total of 3728 uCyt+ tests were URINARY DIVERSION AFTER RADICAL
performed. The sample was considered positive also when CYSTECTOMY IN PATIENTS WITH TRANSITIONAL
there was 1 to 4 positive red and/or green fluorescent cells on CELL CARCINOMA OF THE BLADDER
the slide (Borderline Positive). A case was considered positive
Roberto Nucciotti1, Alessandro Bragaglia2,
when there were ≥5 positive cells on the slide. Results: uCyt+
Fabrizio Viggiani2, Fabio Massimo Costantini2,
was Borderline Positive in 135 cases where traditional
Francesco Mengoni2, Giandomenico Passavanti2,
cytology was negative: 85 cases (62,3%) were false positives;
Valerio Pizzuti2
50 cases (37%) were true positives, which were confirmed
during the successive cystoscopies repeated over time. This 1U.O. Urologia Scuola Di Chirurgia Mininvasiva E Robotica
gave the possibility to anticipate diagnosis of UC to ≤12 Ospedale Della Misericordia;
months in 88% and to >12 months in 12%, (median 8 months. 2U.O. Urologia Ospedale Della Misericordia, Grosseto, Italy

Discussion and Conclusion: A delayed diagnosis of UC can

have important relapses on patient life quality and in some Robot-assisted radical cystectomy (RARC) and laparoscopic
cases on their survival. There are new laboratory strategies and radical cystectomy (LRC) are becoming increasingly
methods available to perform along side with urinary cytology widespread for the treatment of bladder tumor. We present our
and cystoscopy, such as uCyt+ that could help to correct the technique of intracorporeal urinary diversion and present
insufficiencies present in the current bladder cancer oncological and functional outcomes focusing specifically on
management. According to literature, the uCyt+ test, [FDA the oncologic parameters and comorbidity of the procedures.
approved in the surveillance of UC patients (1)] in Patients and Methods: Single hospital case series from 2009 to
combination with traditional cytology increases diagnostic 2011 including 23 selected patients with high grade and/or
sensibility over 40%. The non-invasive uCyt+ test has the muscle invasive urothelial cancer of the bladder without
advantage of not provoking any collateral effects with repeated clinical evidence of lymph-node involvement and an American
use. In fact, UC develops more frequently in ages when other Society of Anesthesiologists (ASA) score <4. Group A (N=16)
illnesses are present and when frequent invasive cystoscopies underwent robotic intracorporeal neobladder after robotic
are generally performed in narcosis. Furthermore, an eventual radical cystectomy, whereas group B (N=6) underwent
reduction of non essential instrumental exams, not only laparoscopic ileal conduit after laparoscopic cystectomy. The
reduces bladder trauma, that repeated over time, could behave two groups were demographically comparable. We evaluated

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

the mean age, clinical stage, operative time, blood loss, subtypes of our group were: clear cell carcinoma 84 (80.02);
intraoperative complications and transfusions, type of papillary 17 (16%); cromophobe 2 (1.9%); NAS 2 (1.9%).
diversion, time of catheterization, analgesic consumption, start Lymphadenectomy was performed in 80 patients. The
of oral nutrition, rate of postoperative complications, length of Furhman Grading was G2 25(24.5%); G3 57 (53.8%); G4
hospital stay, pathologic diagnosis of the specimen, number of 23(21.7%). Lymph node involvement was present in 15
lymph nodes removed, and the oncologic outcome Results: patients and distant metastases were present in 17 patients. We
The mean operative time was 320 minutes (range: 280-380 observed a better prognosis in group A than in group B, with
min) for group A and 280 minutes (range: 260-310 min) for a significant difference between the two groups (p=0.024)
group B. The mean blood loss was 640 mL (range: 370-810 (Figure 1).
mL) in group A and 410 mL (range: 300-650 mL) in group B.
The mean of lymph nodes removed was 18 (range: 16-21) for
group A and 13 (range: 11-16) for group B. Five patients were
diagnosed with positive lymph nodes. Surgical margins were
clear in all but one patient. Early complications occurred in 8
patients. Median postoperative stay was 14 d (range: 12-18).
Conclusion: Laparoscopy/ robotic assisted radical cystectomy
and minimally invasive intracorporeal urinary diversion is a
safe procedure, like open surgery, but it offers the advantage of
minimal invasiveness, represented by reduced analgesic
consumption and early recovery of peristalsis with rapid oral
nutrition.

22
PROGNOSTIC ROLE OF INFILTRATION OF THE
HILAR FAT IN PATIENTS WITH RCC IN STAGE T3A
G.C. Rocca, R. Schiavina, E. Brunocilla, A. Bertaccini,
M. Garofalo, S. Concetti, G. Saraceni, F. Chessa, C.N.
Bizzarri, Z. Zukerman, C.V. Pultrone, L. Bianchi,
A. Farina, G. Martorana
Department of Urology, S. Orsola-Malpighi Hospital,
University of Bologna, Bologna, Italy
At multivariate logistic regression analysis, the new grouping
Introduction: Outcome prediction in renal cell cancer (RCC) was not an independent prognostic factor, while the
remains controversial; only a few prognostic parameters have pathological size and the Furhman Grade were independent
achieved a widespread acceptance in clinical practice. The adverse prognostic parameters. Conclusion: The present
prognostic significance of perirenal fat or sinus fat infiltration results in accordance with the results in the literature show a
in patients with renal cell carcinoma (RCC) has attracted prognostic difference between the various subgroups in the
several controversies in the current literature. Patients and same category of TNM, suggesting the need of a new
Methods: The pathological data and clinical follow-up of 593 classification. Large prospective series are needed to validate
patients who underwent radical or partial nephrectomy for these findings.
RCC from 2000 to 2011 at our institution were analyzed.
Among these, we selected 105 patients with pT3 RCC
dividing them into 2 groups: group A (44 patients) with
23
peritumoral fat invasion, group B (61 patients) with
INTRAVESICAL ADJUVANT ELECTROMOTIVE
peritumoral fat and hilous fat involvement. We evaluated the
MITOMYCIN-C IN PATIENTS WITH PRIMARY
cancer specific survival (CSS) between the two groups using
INTERMEDIATE-RISK NON-MUSCLE INVASIVE
Kaplan Meier survival curves for the univariate analysis and
BLADDER CANCER: A RANDOMIZED
Cox regression model for multivariate analysis. Results: The
CONTROLLED TRIAL
median survival was 32 months; the mean age was 64.75 (SD:
11.50), the mean tumor size was 7.25 cm (SD 2.77). The mean Cristian Verri1, Emanuele Liberati2, Luca Topazio1,
follow-up was 42.63 months (SD 35.14). The histological Marco Valenti3, Savino Mauro Di Stasi1

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

1Dipartimento Di Scienze Chirurgiche/Urologia Università 24

Tor Vergata, Roma; INTRAVESICAL SEQUENTIAL BCG
2U.O.S. Di Urologia Oncologica Policlinico Casilino, Roma; AND ELECTROMOTIVE MITOMYCIN-C
3Dipartimento Di Medicina/epidemiologia Università De VERSUS BCG ALONE FOR STAGE PT1
L’Aquila, L’Aquila, Italy UROTHELIAL BLADDER CANCER
Emanuele Liberati1, Cristian Verri2, Luca Topazio2,
Background: In laboratory and clinical studies, intravesical
Marco Valenti3, Savino Mauro Di Stasi2
electromotive drug administration (EMDA) increased
mitomycin-C (MMC) bladder uptake, improving clinical 1U.O.S. Di Urologia Oncologica Policlinico Casilino;
efficacy in high-risk non-muscle invasive bladder cancer 2Dipartimento Di Scienze Chirurgiche/urologia Università
(NMIBC). Our aim was to compare transurethral resection Tor Vergata, Roma;
of bladder tumor (TURBT) and adjuvant intravesical 3Dipartimento Di Medicina/epidemiologia Università De

electromotive EMDA/MMC with TURBT and adjuvant L’Aquila, L’Aquila, Italy

intravesical passive diffusion (PD) MMC and TURBT
alone in patients with intermediate-risk NMIBC. Methods: Background: In 2006, we reported that intravesical, sequential
From January 1994 to December 2003, 225 patients with Bacillus Calmette-Guérin (BCG) and electromotive mitomycin
primary intermediate-risk NMIBC were randomly assigned in patients with stage pT1 urothelial bladder cancer leads to
to: TURBT alone (n=75), TURBT and adjuvant higher disease-free interval, lower recurrence and progression,
intravesical 40 mg PD/MMC dissolved in 50 ml sterile and to improved overall survival and disease-specific survival
water infused over 60 minutes once a week for 6 weeks compared with BCG alone. After an additional 6 years of
(n=77), or TURBT and adjuvant intravesical 40 mg follow-up, we now report estimated 16-year results. Methods:
EMDA/MMC dissolved in 100 ml sterile water with 23 From January 1994 through June 2002, we randomly assigned
mA pulsed electric current for 30 minutes once a week for 212 patients with stage pT1 urothelial bladder cancer to 81 mg
6 weeks (n=73). Patients in the intravesical adjuvant BCG infused over 120 min once a week for 6 weeks (n=105)
EMDA/MMC and PD/MMC groups who were disease-free or to 81 mg BCG infused over 120 min once a week for 2
3 months after induction treatment, were scheduled to weeks, followed by 40 mg electromotive mitomycin
receive monthly intravesical instillation for 10 months, (intravesical electric current 20 mA for 30 min) once a week
with the same dose and methods of infusion as initial as one cycle for three cycles (n=107). Complete responders
assigned treatment. All patients were assessed for safety. underwent maintenance treatment: those assigned BCG alone
Our primary endpoints were recurrence rate and disease- had one infusion of 81 mg BCG once a month for 10 months,
free interval. Analyses were done with the intention to and those assigned BCG and mitomycin had 40 mg
treat. Results: Median follow-up was 86 months (IQR 53- electromotive mitomycin once a month for 2 months, followed
123). Patients assigned to receive TURBT and adjuvant by 81 mg BCG once a month as one cycle for three cycles.
intravesical EMDA/MMC had a lower rate of recurrence The primary endpoint was disease-free interval; secondary
(26/73 [36%]) than those assigned to receive TURBT and endpoints were time to progression, overall survival, and
adjuvant intravesical PD/MMC (46/77 [60%]) and TURBT disease-specific survival. Analyses were done by intention to
alone (47/75 [63%]; log-rank p<0.0004). Patients assigned treat. Results: Median follow-up was 121 months (IQR 70.5-
to receive TURBT and adjuvant intravesical EMDA/MMC 163.5). Patients assigned sequential BCG and electromotive
also had a higher median disease-free interval (19 months, mitomycin had higher disease-free interval than did those
95%CI 11-27) than those assigned to receive TURBT and assigned BCG alone (79 months [95% CI 27-139] vs. 26
adjuvant intravesical PD/MMC (10.5 months, 10-16) and months [11-113]; difference between groups 53 months [39-
TURBT alone (10 months, 7-13; log-rank p<0.0001). In 67], log-rank p=0.0002). Patients assigned sequential BCG
patients who underwent adjuvant intravesical MMC local and electromotive mitomycin also had lower recurrence (45%
side-effects and symptoms were recorded in 19/77 (25%) [35-55] vs. 62% [50-72], difference between groups 17% [6-
in the PD/MMC group, and in 19/73 (26%) in the 28], log-rank p=0.0002); progression (12% [3-21] vs. 28%
EMDA/MMC group. Treatment was stopped because of [17.5-38.5], difference between groups 16% [5-27], log-rank
chemical cystitis side-effects in 3/77 (4%), and 1/73 (1%) p=0.003); overall mortality (44% [33-55] vs. 59% [43-75],
patients of these groups, respectively. Conclusion: difference between groups 15% [2-28], log-rank p=0.01); and
Adjuvant Intravesical EMDA/MMC is feasible and safe; disease-specific mortality (9% [2.5-15.5] vs. 23% [11–34],
moreover, it reduces recurrence rates and enhances the difference between groups 14% [4-24], log-rank p=0.0055).
disease-free interval in patients with intermediate-risk Side effects were mainly localised to the lower urinary tract.
NMIBC compared with TURBT and adjuvant intravesical Conclusion: In patients with stage pT1 urothelial bladder
PD/MMC and TURBT alone. cancer intravesical BCG combined with electromotive

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

mitomycin provided better results than BCG alone in terms of 26

higher remission rates and longer remission times. HETEROGENEOUS NUCLEAR
RIBONUCLEOPROTEIN K AND ANDROGEN
RECEPTOR EXPRESSION IN RADICAL
25 PROSTATECTOMY SPECIMENS
CLINICAL STAGE I SEMINOMA: ARE ASSOCIATED WITH PROGNOSIS
LONG TERM EXPERIENCE OF
Paola Barboro1, Sandra Salvi2, Alessandra Rubagotti3,
A PATIENT ORIENTED STRATEGY
Simona Boccardo2, Bruno Spina2, Mauro Truini2,
Teodoro Sava, Antonio Porcaro Giorgio Carmignani4, Carlo Introini5,
Francesco Boccardo3, Cecilia Balbi1
Oncologia Do Aoui Verona, Italy
1Traslazionale Urologica IRCCS Azienda Ospedaliera
Introduction: Clinical stage I seminoma is a relatively rare Universitaria San Martino IST-Istituto Nazionale Per La
disease with a very favourable prognosis. Different options are Ricerca Sul Cancro;
available (surveillance, radiotherapy or chemotherapy): all of 2Anatomia e Citoistologia Patologica IRCCS Azienda

them have excellent results but are characterized by possible Ospedaliera Universitaria San Martino IST-Istituto Nazionale
side-effects. No clear prognostic factors are demonstrated and Per La Ricerca Sul Cancro;
guidelines suggest that the choice of the best strategy is 3Oncologia Medica B IRCCS Azienda Ospedaliera

primarily related to the patient-doctor discussion. We Universitaria San Martino IST-Istituto Nazionale Per La
retrospectively analyzed our experience: till 2001 the preferable Ricerca Sul Cancro; Dipartimento Di Medicina Interna,
strategy was radiotherapy (but from 1997 surveillance was also Università Di Genova;
offered); from 2002 we offered to clinical stage I seminoma 4Clinica Urologica Dipartimento di Urologia “Luciano

patients, after an exhaustive discussion, to choose between one Giuliani”, Università Di Genova;
of the 3 options (surveillance, radiotherapy or chemotherapy). 5Oncologia Urologica IRCCS Azienda Ospedaliera

Patients and Methods: 133 patients were retrospectively Universitaria San Martino IST-Istituto Nazionale Per La
reviewed: 79 treated with orchiectomy from 1982 to 2001 and Ricerca Sul Cancro, Italy
54 after 2002. All of them had pure seminoma clinical stage I
disease. Before 2001, patients were treated as follows: 61 with Introduction: Prostate carcinoma (PCa) represents a major
adjuvant radiotherapy, 16 with surveillance, 1 with health concern in the Western Countries and new diagnostic
chemotherapy and 1 with retroperitoneal lymphadenectomy. and prognostic biomarkers, able to supplement or replace
After 2002 the treatment option has been primarily indicated serum PSA testing, are strongly required from clinicians to
by the patient, irrespectively of prognostic factors: 30 adopted improve risk stratification of patients with this tumor.
a surveillance program, 22 were treated with radiotherapy and Recently, studies carried out in our and in other
2 with chemotherapy. Results: 13 patients relapsed: 5 were laboratories, have shown that heterogeneous nuclear
primarily treated with radiotherapy, 1 with chemotherapy and 7 ribonucleoprotein K (hnRNP K) may play a key role in the
during the surveillance strategy. Only 2 patients died (both carcinogenesis process in PCa since it is implicated in the
before 1994) and only one due to the disease. From 2002 most network of mechanisms that control androgen receptor
of patients preferred a surveillance program (55%; while (AR) expression (1, 2). Moreover, in human prostate
radiotherapy 40%); very few opted for adjuvant chemotherapy. LNCaP cells, AR and hnRNP K colocalize in the
From 2008, 88% of patients seen (29 out of 33) opted for the nucleoplasm in a complex that is highly proximal to DNA
surveillance program. The main patient’s reason for choosing a (3). A lot of human tumors present an overexpression of
surveillance program is to avoid unnecessary treatment and hnRNP K and in several cases an aberrant cytoplasmic
side-effects; the reasons for those who opted for radiotherapy localization as well; besides a correlation between the
are to simplify the follow-up (reduce the number of visits and protein expression and patient’s prognosis was also
CT scan) and the fear of recurrence. Discussion: Surveillance observed. In the present study we have analyzed, in radical
seems to be an optimal strategy both for patients and in our prostatectomy specimens, hnRNP K and AR expression to
experience. Often more patients prefer the surveillance option; evaluate their diagnostic and prognostic potential and
some patients still decide for an active adjuvant treatment, whether, in vivo, a relationship between the expression of
mainly radiotherapy, usually in order to reduce the fear of the two proteins exists. Patients and Methods: From 1995
recurrence and the number of visits and CT scans. to 2007, 105 patients who had undergone a radical
prostatectomy for biopsy proven PCa, were selected.
1 Consoli F, Sava T and Cetto GL: Clinical Stage I seminoma. Immunohistochemistry was carried out using anti-hnRNP
Tumori 94(1): 1-6, 2008. K and anti-AR antibodies. For each patient both PCa and

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

adjacent non-cancer tissue were examined. Biochemical 27

progression-free (BPF) and overall survival (OS) were the PROGNOSTIC PREDICTORS FOR TIME TO
main end-points of the present analysis. Patients were CLINICAL PROGRESSION AND CASTRATION
followed at regular intervals and PSA determined. A PSA RESISTANCE IN PROSTATE CANCER CASES WITH
level of at least 0.4 ng/ml, which was confirmed by another BIOCHEMICAL PROGRESSION AFTER SURGERY
assay four weeks later, was sufficient to indicate a TREATED WITH INTERMITTENT ANDROGEN
biochemical progression. After a median follow-up time of DEPRIVATION (IAD)
10.7 years (95% confidence interval (CI) 9.7-11.6), 54
Alessandro Sciarra, Stefano Salciccia,
patients were found to have experienced biochemical
Francesco Minisola, Alessandro Gentilucci,
progression and 21 died. BPF and OS were calculated by
Andrea Alfarone, Susanna Cattarino,
means of the Kaplan–Meier method and curves compared
Michele Innocenzi, Michele Ravaziol,
by the log-rank test. In order to evaluate the possible
Vincenzo Gentile
interactions among all the variables under study, multi-
parametric models were constructed according to Cox’s Dipartimento di Urologia U. Bracci Policlinico Umberto I,
technique. All the analyses were performed using SPSS Roma, Italy
version 18.0 for Windows. Results: In PCa, hnRNP K
displayed a more frequent and stronger immunoreactivity, Abstract Objective: To define characteristics of the first cycle
both cytoplasmic and nuclear, when compared with of intermittent androgen deprivation (IAD) that would
adjacent non-cancer tissue (p=0.0001). The patients with predict outcomes in a long term follow-up. Patients and
higher cytoplasmic expression (score ≥6) showed a highest Methods: In 1996 we started a prospective study of IAD for
risk of biochemical failure (HR=1.63, 0.84-3.16 CI 95%) the treatment of biochemical progression (BP) after radical
and death (HR=2.23, 0.86-5.81 CI 95%) which, however, prostatectomy (RP) for prostate cancer (PC). The end-points
were statistically significant only in the subgroup (n=30) of of the trial were time to clinical progression (CP) and time to
patients that have been submitted to neoadjuvant endocrine castration resistance PC (CRPC). Eighty-four cases were
therapy (HR=3.33, 1.24-8.97 CI 95%, p=0.017). Despite included in the study. In all cases, after an initial induction
AR expression was much variable, an elevate percentage of period, an acceptable nadir to switch from on-to-off-phase of
AR positive cells (>75%), in the tumor tissue, was IAD was considered to be a serum PSA <1.0 ng/ml.
associated with a better prognosis (HR=0.29, 0.13-0.69 CI Measurements: As possible predictors for time to CP and
95%, p=0.005) and multivariate analysis indicated an CRPC, we analyzed pretreatment parameters such as age,
independent prognostic value for the AR even with respect Gleason Score, serum PSA, testosterone, chromogranin A
to Gleason score, seminal vesicles and surgical margins (CgA) levels, and characteristics from the first cycle of IAD.
involved, capsular penetration, PSA, pN, and neoadjuvant Results: Mean follow-up during IAD was 88.6±16.7 months;
therapy (HR=0.28, 0.110,69 CI 95%, p=0.006). A direct 29.7% of patients developed CRPC and 14.2% of cases
correlation between nuclear hnRNP K expression and AR showed a CP with a mean time of 88.4±14.3 months and
level was observed (p=0.005), suggesting a possible 106.5±20.6 months, respectively. At univariate and
interaction between the two proteins in the nucleoplasm. multivariate analysis, the PSA nadir during the first on-phase
Finally, lower AR (≤75%) and higher citoplasmic hnRNP period and the first off-phase interval resulted in significant
K (score ≥6) were associated with poor OS (HR=1.71, and independent predictors (p<0.001) of the time to CRPC
0.97-51.97 CI 95%, p=0.055). Conclusion: Our finding and CP. In particular for cases with a PSA nadir >0.4 ng/ml
confirms that, also in PCa, an aberrant cytoplasmic and for those with an off-phase interval </=24 weeks, the
expression of hnRNP K is associated with a poor prognosis. risk of CRPC and CP during IAD was 2.7-2.5 and 3.0-3.1
The pivotal role played by this protein might depend on a times that for patients with a PSA nadir </=0.1 ng/ml and
direct interaction with AR and/or on a control exerted on with an off-phase interval >48 weeks, respectively.
its expression. Moreover, cytoplasmic higher level of Conclusion: Cases with BP after RP selected to IAD that
hnRNP K and lower percentage of AR positive cells were show at the first cycle a PSA nadir </=0.1 ng/ml and a off-
associated with shorter OS and therefore might be potential phase interval >/=48 weeks may identify candidates who will
prognostic markers for PCa. Additional validation studies experience better response to IAD treatments and delayed CP
should be justified. or CRPC development.

1 Barboro P et al: Br. J. Cancer 100: 1608-1616, 2009.

2 Mukhopadhyay NK et al: Cancer Res 69: 2210-2218, 28
2009. PROSTATE CANCER UNITS FOR THE OPTIMAL
3 Barboro P et al: Prostate 71: 1466-1479, 2011. MANAGEMENT OF PROSTATE CANCER

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Alessandro Sciarra, Stefano Salciccia, same pathologist. Methods: We retrospectively reviewed all
Francesco Minisola, Alessandro Gentilucci, histopathological examinations performed during 20 years
Andrea Alfarone, Susanna Cattarino, in patients undergoing surgery in our urological clinic who
Michele Innocenzi, Michele Ravaziol, Vincenzo Gentile were diagnosed with BPH. We limited our evaluation to the
following variables in each BPH case analyzed:
Dipartimento di Urologia [Link] Policlinico Umberto I, inflammatory aspects associated with BPH, presence of
Roma, Italy focal acinar atrophy, atypical adenomatous hyperplasia
(AAH), prostatic intraepithelial neoplasia (PIN), incidental
Prostate cancer (PC) is established as one of the most prostate carcinoma (IC). These histological variables were
important medical problems affecting the male population. analyzed according to some clinical parameters such as age,
An early diagnosis is necessary to implement well-balanced prostate volume and serum PSA. Results: The study
therapeutic options, and the correct evaluation can reduce population was comprised of 3942 cases with histological
the risk of overtreatment with its consequential adverse diagnosis of BPH. The mean patient age was 68.85±7.67
effects. Breast and prostate cancers, respectively, are the years. In particular, inflammatory aspects were associated
most common cancers in women and in men, and various with BPH in a high percentage of cases (43.1%=1700
similarities have been underlined. The paradigm of the cases), predominantly as chronic inflammation. Observation
patient consulting a multidisciplinary medical team has been of focal acinar atrophy significantly increased according to
an established standard approach in treating breast cancer. patient decade of age (p=0.027). There was a significant
Such multidisciplinary approach can offer the same optional trend to increase with age decades (p=0.036) for high grade
care for men with PC as it does for women with breast PIN. A significant difference was found in IC (T1a, T1b)
cancer. A multidisciplinary team (MDT) comprises distribution in the different decades of age and especially in
healthcare professionals from different disciplines whose regards to both T1a and T1b tumors, there was a trend to
goal of providing optimal patient care is achieved through increase with patient age (p=0.020 and p=0.025,
coordination and communication with one another. A respectively). On the contrary, the distribution of
Prostate Cancer Unit is a place where men can be treated by inflammatory aspects (p<0.001) and AAH (p=0.003)
specialists in PC, working together with a multi-professional significantly varied according to prostate volume, and
team. The MTD approach guarantees a higher probability particularly in regards to chronic inflammation, there was a
for the PC patient to receive adequate information on the trend to increase depending on the prostate volume
disease and on all possible therapeutic strategies, balancing (p=0.002). Only the presence of T1b tumor but not of the
advantages and related side-effects. The future of PC other histological parameters associated to BPH, was able
patients relies on a successful multidisciplinary to significantly influence serum PSA. Conclusion: In our
collaboration between experienced physicians, which can analysis different histological variables associated to BPH
lead to important advantages in all the phases and aspects are differently influenced by the age of patients and prostate
of PC management. A Prostate Cancer Unit has been volume, and they differently influence serum PSA levels.
established from 2010 in our department and our results
confirm these positive suggestions.
30
COMBINATION THERAPY OF
29 ETHINYLESTRADIOL AND
DISTRIBUTION OF INFLAMMATION, ESTRAMUSTINE PHOSPHATO
PRE- MALIGNANT LESIONS AND INCIDENTAL REINTRODUCES OBJECTIVE CLINICAL
CARCINOMA IN HISTOLOGICALLY RESPONSES IN PATIENTS WITH CASTRATE-
CONFIRMED BENIGN PROSTATIC HYPERPLASIA: RESISTANT PROSTATE CANCER
A RETROSPECTIVE ANALYSIS
Gian Maria Busetto1, Alessandro Sciarra2,
Alessadro Sciarra, Stefano Salcicca, Francesco Minisola, Stefano Salciccia2, Vincenzo Gentile2, Franco Di Silverio2
Alessandro Gentilucci, Andrea Alfarone, Susanna Cattarino, 1Urology Sapienza Rome University;
Michele Innocenzi, Michele Ravaziol, Vincenzo Gentile 2Clinica Urologica Policlinico Umberto I, Roma, Italy
Dipartimento di Urologia U. Bracci Policlinico Umberto I,
Roma, Italy Introduction: Therapy for advanced prostate cancer centers on
suppressing systemic androgens and blocking activation of the
Objectives: We analyze our experience on BPH through 20 androgen receptor (AR). Despite anorchid serum androgen
years of histopathological examinations performed by the levels, nearly all patients develop castration-resistant disease.

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We hypothesized, on the basis of an ancient experience (1), prostate cancer: a mechanism for castration-resistant tumor
that ongoing steroidogenesis within prostate tumors and the growth. Cancer Res 68: 4447-4454, 2008.
maintenance of intratumoral androgens may contribute to 3 Yap TA, Carden CP, Attard G and de Bono JS: Targeting
castration-resistant growth. Recently Montgomery and CYP17: established and novel approaches in prostate cancer.
colleagues (2), in a basic research convincingly showed that Curr Opin Pharmacol 8: 449-457, 2008.
median testosterone levels within metastases from castrated 4 Tindall DJ and Rittmaster RS: The rationale for inhibiting
men are approximately threefold higher than levels within the 5α-reductase isoenzymes in the prevention and treatment of
primary prostate cancers from untreated eugonadal men. The prostate cancer. J Urol 179: 1235-1242, 2008.
authors further showed up-regulated expression of
steroidogenic enzymes including FASN, CYP17A1, HSD3B1,
HSD17B3, CYP19A1, and UGT2B17 (p<0.001 for all). 31
Indeed, several clinical studies have proposed minimizing ENDOVESICAL ADJUVANT THERAPY
levels of these extragonadal sources of T and its precursors by FAILURE IN HIGH-RISK NON MUSCLE
using combinations of inhibitors targeting different points of INVASIVE BLADDER CANCER (NMIBC):
steroidogenesis such as ketoconazole and 5-α reductase CHEMOSENSITIVITY TESTING
inhibitors (3, 4). We evaluated whether a combination therapy AND TAYLOR THERAPY
of ethinylestradiol and estramustine phosphato can reintroduce
Gian Maria Busetto1, Riccardo Giovannone2,
objective clinical responses in patients with metastatic
Arianna Petracca3, Chiara Nicolazzo3, Paola Gazzaniga3,
androgen ablation refractory prostate cancer (HRPC).
Vincenzo Gentile2, Ettore De Berardinis2
Materials and Methods: 12 patients (5 pz Gleason score 8
(4+4), 5 pz Gleason score 9 (5+4), 2 pz Gleason score 10 1Urology Sapienza Rome University;
(5+5)) with stage D3 disease and bone metastases who had 2Clinica Urologica Policlinico Umberto I, Roma;
progression despite initial responses to combined androgen 3Dipartimento Di Biochimica E Biologia Molecolare

blockade and in whom antiandrogen withdrawal subsequently Policlinico Umberto I, Roma, Italy
failed discontinued combined androgen blockade and received
2 mg ethinylestradiol orally daily and oral estramustine 420 Introduction and Objectives: Adjuvant endovesical treatment
mg/daily. Serum prostate specific antigen (PSA), Eastern of choice for high risk NMIBC is still debated and still open
Cooperative Oncology Group performance status and bone questions are: Which drug? Which dosage? Which therapy
pain scores were assessed at regular intervals. Median follow- planning? Although intravesical chemo-immuno treatments is
up was 17 months (range 8 to 26). Results: All cases (90%, the gold standard after TURB the percentage of recurrence and
95% CI 55.5 to 99.8) had an objective clinical response, progression is still high. Making a systematic overview of
defined as a greater than 50% PSA decrease (median 87.1%, chemotherapy effects in urothelial bladder comprising 31974
range 50.2% to 94.4%). PSA normalization (less than 4 patients we have up to 60% of recurrences at 5-8 years.
ng/ml) was achieved in 3 cases. All patients reported Analysing BCG failure we have up to 54% of reccurences at 5
significant and durable improvement in bone pain (median years. There is really need to introduce the concept of
duration 17.5 months) and performance status (median personalized medicine in bladder cancer management and in
duration 18 months). The most important side-effects were: particular with molecular and genetic testing we should be able
vein thrombosis (3 pz) and gastric pain (2 pz). Conclusion: to predict which patients are at high risk for cancer progression
Castrate resistant prostate cancer (CRPC) is sensitive to and which patients will respond to treatment. Materials and
androgens and moreover prostate cancer could become Methods: It has been reported that some chemotherapy drugs
hypersensitive to low levels of androgens and is finally used in intravesical regimens may induce a phenomenon
established that this cancer produces androgens by itself. For known as chemotherapy-induced resistance (CIR), through the
the future the therapy could involve increasing estrogen dose up-regulation of ATP-binding cassette proteins. Furthermore,
(Estradurin® 80 mg ?) and/or using new androgen antagonist inefficient apoptotic machinery might also lead to
(abiraterone acetate, MDV300 ?). IAS (intracrine androgen chemotherapy resistance, through the selection of more
synthesis) produces a “relative hormone refractoriness” and is aggressive clones that, proliferating in the presence of the drug,
the new research frontier. may be responsible of progression of disease under treatment.
We started a clinical trial with the aim to characterize, in each
1 Di Silverio F, Gagliardi V, Sorcini G and Sciarra F: patient, an individual chemosensitivity profile, based on the
Biosynthesis and methabolism of androgenic hormones in expression of a panel of markers that are involved in the
cancer of the prostate. Invest Urol 13(4): 286-288, 1976. resistance to standard chemotherapy drugs. Specifically, we
2 Montgomery RB, Mostaghel EA, Vessella R et al: chose multidrug resistance protein 1 and 2 (MRP1, MRP2),
Maintenance of intratumoral androgens in metastatic belonging to the superfamily of ATP-binding cassette

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transporters, which are both involved in the resistance to greater than 50%. Furthermore, some non-muscle-invasive
epirubicin, doxorubicin and mitomycin-C; human equilibrative bladder cancer (NMIBC), more frequently T1G3, present with
nucleotide transporter 1 (hENT1) and deoxycytidine kinase biological features of invasiveness, leading to cancer death
(dCK), involved in the resistance to gemcitabine and α5β1 after bladder-sparing treatment within 5 years in about 16-23%
integrin, which represents the fibronectin receptor, and is of cases. Circulating tumor cells (CTCs) play a crucial role for
involved in the internalization of BCG. The present analysis distant failure in different types of solid tumors. Their
was also extended to apoptosis regulating genes, such as the enumeration through Cell Search system (Veridex) is widely
bcl-2/bax ratio and surviving expression. 128 patients with high used for prognostic information in patients with metastatic
risk NMIBC were enrolled, all candidates for TUR-B followed breast, colon and prostate cancer. Recent studies have shown
by intravesical treatment. One mg of tumoral tissue from each that CTCs are released in circulation in a very early phase of
patient was kept for molecular assay subjected to RNA cancer disease where their presence is associated with a worse
extraction and RT-PCR amplifications with primers specific for prognosis of patients and CTC count could reflect the ongoing
these components. On the basis of densitometric analysis of the progression of cancer disease. Patients and Methods: Primary
amplification bands obtained by normalisation with the endpoint of the present study was to investigate the prognostic
GAPDH internal controls, we obtained for each patient a significance of CTCs in NMIBC patients; to this purpose the
chemosensitivity molecular profile. We considered high, presence of CTCs has been used to predict time to first
intermediate and low sensitivity to mitomycin c, epirubicin, recurrence (TFR) and time to progression (TTP) in a follow-
and doxorubicin a ratio MRP/GAPDH <1, =1, >1 respectively. up of 24 months. Secondary endpoints were the association
For gemcitabine resistance, we considered sensitivity, between CTC presence and known prognostic variables such
intermediate sensitivity and resistance a ratio hENT- as T, G and presence of CIS. In a prospective study, 44
dCK/GAPDH >1, =1 and <1 respectively. Sensitivity to BCG patients were enrolled all with histopathological diagnosis of
was evaluated as follows: high, intermediate, low sensitivity in NMIBC. According to T, 18/44 (41%) were Ta and 26/44
the presence of α5β1/GAPDH >1; =1; <1 respectively. We then (59%) were T1. 9/44 (20%) were G1, 9/44 (20%) were G2
compared both the molecular profiles of chemosensitivity to and 26/44 (59%) were G3. Concomitant presence of CIS was
the clinical response to the intravesical regimen adopted in the found in 8/44 (18%) patients. A population of 20 healthy
first 6 months of follow-up. Results: This chemosensitivity test donors was included as negative control when needed. Blood
was able to predict response to treatment in 93% of patients. drawings were carried out in all patients at the first diagnosis,
The assay is easy to perform with low costs and rapid time of 1h before TURB. Patients were then included in a follow-up
execution. Conclusion: Our results are encouraging in the view programme which consisted of cystoscopy and urinary
of an individualised therapeutic approach, to provide a higher cytology every 3 months and a URO-CT every 12 months.
treatment success rate while sparing patients unnecessary CellSearch system (Veridex) was used for CTCs enumeration.
toxicity from drugs that are not suited for their tumors. Briefly, the method is an immunomagnetic cell enrichment
which uses antibodies targeting epithelial cell adhesion
molecule (EpCAM) and nucleus labeling with fluorescent dye.
32 Results: CTC were detectable in 8/44 patients (18%), and in
PROGNOSTIC VALUE OF CIRCULATING TUMOR 0/20 healthy volunteers. CTC were found in 8/26 (31%)
CELLS IN NON MUSCLE INVASIVE BLADDER patients with T1 tumors, and in 0/18 patients with Ta
CANCER: A CELL SEARCH ANALYSIS (p=0.0275). CTC presence was also found associated to
concomitant presence of CIS; in the group of patients with
Paola Gazzaniga1, Angela Gradilone2,
CIS, CTC were found in 5/8 (62.5%) compared to 3/36 (8.3%)
Ettore De Berardinis3, Chiara Nicolazzo2,
found in the group without CIS (p=0.00228). For what
Arianna Petracca2, Alessio Farcomeni2,
concerns TTP, of the 8 CTC+ patients, 7 experienced the event
Gian Maria Busetto3, Vincenzo Gentile3,
within the end of follow-up, with a median TTP of 12 months.
Luigi Frati4, Enrico Cortesi4
No events were observed in the 36 CTC- patients (p<0.001).
1Experimental Medicine Sapienza Rome University; For what concerns TFR, there were once again 7 events in the
2Dipartimento Di Biochimica E Biologia Molecolare CTC+ group within end of follow-up, with a median TFR of
Policlinico Umberto I, Rome; 13 months and 13 events in the CTC- group. Conclusion:
3Clinica Urologica Policlinico Umberto I, Rome; Evaluation of circulating tumor cells from blood could provide
4Incologia Medica B Policlinico Umberto I, Rome, Italy a non-invasive source of representative tumor material;
although the prognostic significance of CTC count has been
Introduction: Although most cases of bladder cancer patients more extensively validated in a metastatic setting, a growing
present with a disease that is confined to mucosa (Ta) or body of evidence is now demonstrating their role in early
submucosa (T1), recurrence rate in this cohort of patients is staged tumors as well. We suggest that NMIBC patients with

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similar stage and detectable CTCs may be considered at biopsy with less than 10 cores and cases in which a MR with
higher risk for recurrence and progression, and therefore be a complete MRSI and DCEMR study was not possible. All the
candidates for more accurate surveillance and more aggressive patient were submitted to1H-MRSI/DCEMR; before that
treatment options. patient’s urine were collected by an expert Urologist,
following an attentive prostate massage (3 compressions for
each prostatic lobe), in order to perform PCA3 assay. All the
33 biopsies were performed according to a standard biopsy
MULTIPARAMETRIC MAGNETIC RESONANCE protocol: 10-core laterally directed random TRUS-guided
IMAGING OF THE PROSTATE AND PCA3 prostate biopsy (two cores from the basal portion lateral and
URINARY TEST: IS TIME TO RE-EVALUATE paramedial, two from the midgland lateral and paramedial, and
PROSTATE BIOPSY? one from the apex, on each side of the gland) for each patient,
plus additional biopsies from other areas suspicious for PCa
Gian Maria Busetto1, Stefano Salciccia2,
at MR. Results: The total number of urinary sediments that
Alessandro Sciarra2, Riccardo Giovannone2,
could be analyzed successfully were 95,3% (41 on 43
Valeria Panebianco3, Ettore De Berardinis2,
specimens). The performance of the PCA3 test was evaluated
Vincenzo Gentile2, Franco Di Silverio2
in terms of sensitivity and specificity by comparing the PCA3
1Urology Sapienza Rome University; score to biopsy results. The overall sensitivity and specificity
2Clinica Urologica Policlinico Umberto I, Rome; of a PCA3 score ≥35 alone for positive biopsy in this cohort
3Dipartimento Di Medicina Sperimentale E Diagnostica were 76.9% and 66.6 %, respectively, with a Positive
Policlinico Umberto I, Rome, Italy Predictive Value (PPV) of 80 % and a Negative Predictive
Value (NPV) of 62.5%; as for MR sensitivity and specificity
Introduction: The deficiencies of serum PSA as a prostate- were, respectively, 92.8% and 86.6% with a Positive Predictive
cancer-specific diagnostic test are well recognized thus Value (PPV) of 92.8 % and a Negative Predictive Value (NPV)
creating a new diagnostic dilemma: only a fraction of men of 86.6%. The sensitivity and specificity of PCA3, MRI and
with increased serum PSA have detectable prostate cancer. their combination were explored using receiver operating
Men with at least one negative biopsy often have persistently characteristic (ROC) analysis. The area under the ROC curve
increased serum PSA, primarily attributable to enlarged gland was 0.755 for PCA3, 0.864 for MR and 0.92 for 1H-
and benign prostatic hyperplasia (BPH). However, a MRSIDCEMR/PCA3. Discussion and Conclusion: Our results
significant proportion of men with slightly increased serum show that the combination of both diagnostic methods may
PSA (2.5-4.0 ng/mL) either have, or will develop, clinically lead to a very high diagnostic accuracy compared to other test
significant prostate cancer [1]. Although biopsy remains the individually. This finding should be confirmed in a large
gold standard for prostate cancer detection, more accurate tests prospective study.
with better specificity are needed to decide whether or not to
biopsy the prostate. In recent clinical trials the potential
diagnostic value of the PCA3 urine test was soon established 34
as well as the role of combined proton 1H-magnetic resonance “THREE-U-STITCHES” TECHNIQUE
spectroscopic imaging (1H-MRSI) and dynamic contrast- FOR URETHROVESICAL ANASTOMOSIS
enhanced imaging magnetic resonance (DCEMR) in the DURING RADICAL PROSTATECTOMY:
management of prostate cancer. The aim of our study is to THE KNOTLESS METHOD
evaluate the ability of 1H-MRSI/DCEMR combined with
Giovanni Zarrelli1, Gian Maria Busetto2,
PCA3 urinary test to improve PCa biopsy detection in cases
Gianluca Mastroprimiano1, Riccardo Giovannone2,
of PSA increase and precious negative prostate biopsy.
Ettore De Berardinis2, Vincenzo Gentile2
Patients and Methods: This is a prospective single-center
study on patients with prior negative random TRUS-guided 1Department of Urology, S.S. Pietro and Paolo Hospital ASL
prostate biopsy and persistent elevated PSA levels. Including VC, Borgosesia (VC);
criteria: a first random TRUS-guided prostate biopsy negative 2Department of Urology, Sapienza Rome University, Rome,

for prostate adenocarcinoma or high-grade prostate Italy

intraepithelial neoplasia, persistent elevated PSA levels (total
PSA ≥4 ng/mL and <10 ng/mL; mean 6.37 ng/mL), and Introduction: The aim of this study was to describe a new
negative digital rectal examination. Exclusion criteria for the technique for urethrovesical anastomosis, which is applicable
study were previous hormonal, surgical, or radiation therapies both in laparoscopy as in open surgery, to accelerate and
for prostate diseases, urine not collected after (digital rectal simplify one of the critical surgical steps during radical
exam) DRE and prior to prostate biopsy, inadequate prostate prostatectomy. Materials and Methods: The technique consists

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in placing three “U” stitches of Monocryl 2-0 between the and overall survival with a median follow-up time of 8.3
bladder neck and urethral stump. The margins are approached years. Results: In Group A patients, 42 recurrences (52.5%)
by double passage of the suture, without performing any node. were reported in a median time of 10.4 months (range 3-26)
The sutures are fixed on the bladder side with application of and 25 progressions (31.2%) in a median time of 25 months
Lapra-Ty clips distant from the joining point of the mucosal (range 3-68). Regarding time to first recurrence and time to
margins. Results: We applied the technique on a total of 116 progression, both the KaplanMeier survival curves obtained
patients that underwent radical prostatectomy, of which 26 are significant and p-values are, respectively, 0.0263 and
open radical retropubic prostatectomy (RRP) and 90 0.0011. Comparing Groups A and B patients, 25 progressions
laparoscopic extraperitoneal radical prostatectomy (LERP). (31.2%) in a median time of 25 months (range 3-68) and 18
With this method we achieved an important reduction of the progressions (25%) in a median time of 25.9 months (range
time needed to complete the anastomosis, particularly in 4-72), respectively, were recorded. Regarding overall survival,
laparoscopy. The optimal combination of the margins, the at 10 years, 24 deaths (42.5%) occurred in a median time of
absence of nodes and the minimum trauma to the urethral wall 55.4 months (range 12-94) in Group A and 42 deaths (58.3%)
enable to create an anastomosis both “sealed” and “tension in a median time of 54.9 months (10-100) in Group B.
free” allowing a quick “welding” of the margins and early Cancer-specific survival was evaluated in Group A with a
catheter removal with a good stretch of the final anastomosis. total of 18 deaths (22.5%) in a median time of 47.5 months
The results are excellent in terms of urinary continence and in (range 16-78), and in Group B with a total of 16 deaths
terms of absence of postoperative stenotic complications. (22.2%) in a median time of 45.7 months (range 16-88). The
Conclusion: The functional results added to ease and speed of progression-free survival Kaplan-Meier curve is not
execution, especially in laparoscopy, make this technique, in significant, the p value being 0.3801; the overall survival
our opinion, a viable alternative to popular anastomotic curve is significant with a p value of 0.0487 while the cancer
techniques. specific survival curve is not significant with a p value of
0.9762. Discussion: In Group A, considering “time to first
recurrence”, the difference is greater between unifocal lesions
35 and multifocal or Cis-associated lesions. Conversely, for
T1G3 HIGH-RISK NMIBC (NON-MUSCLE INVASIVE “time to progression”, there is a greater difference between
BLADDER CANCER): CONSERVATIVE TREATMENT unifocal and multifocal tumours and Cis-associated tumours.
VERSUS IMMEDIATE CYSTECTOMY Looking at “progression-free survival” in Group A and Group
B patients, there is no statistically significant difference, like
Gian Maria Busetto1, Riccardo Giovannone2,
in cancer-specific survival. A statistically significant
Gabriele Antonini2, Vincenzo Gentile2, Ettore De Berardinis2
difference was observed in overall survival being in favour of
1Urology Sapienza University, Rome; conservative treatment thus reflecting that conservative
2Clinica Urologica Policlinico Umberto I, Rome, Italy treatment is not burdened by all the surgical and post-
operative complications of cystectomy. Conclusion: Although
Background: The management of stage T1 poorly NMIBC invading the lamina propria, stage G3, with or
differentiated G3 bladder cancer invading the lamina propria without Cis-associated lesions are burdened both by a high
continues to be debated. These tumours are associated with a volume of recurrences and progressions, cystectomy could be
high risk of recurrence and progression; concomitant considered a too aggressive approach. New biological
carcinoma in situ and/or multifocality are negative prognostic markers are now needed which are able to predict the
factors. Choosing between a preserving approach such as behaviour of the cancer and to guide the decision-making
trans-urethral resection of the bladder (TURB) followed by process between conservative or aggressive treatment.
maintenance bacillus Calmette-Guerin (BCG) and an invasive
approach like cystectomy is critical. Patients and Methods:
Overall, 80 patients underwent TURB and RE-TURB 36
followed by intra-vesical induction treatment with BCG plus ROLE OF PERCUTANEOUS BIOPSY
maintenance (Group A) while 72 patients underwent IN THE DIAGNOSIS OF THE SMALL RENAL
immediate radical cystectomy with extended MASSES: OUR EXPERIENCE
lymphadenectomy (Group B). Patients were divided into 3
Giandavide Cova1, Francesco Beniamin1,
subgroups: uni-focal tumours, multi-focal tumours and
Mauro Dugo2, Luigi Maccatrozzo1
carcinoma in situ associated lesions. In Group A, time to first
recurrence and time to progression were analysed. A 1Urologia Ospedale Regionale Di Treviso;
comparison was made between Group A and Group B 2Nefrologia Dialisi E Trapianto Ospedale Regionale Di
regarding progression-free survival, cancer-specific survival Treviso

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Introduction: The common and widespread use of “imaging” 76-100% concordance of the core to the definitive histological
techniques has increased the incidental diagnosis of small analysis. In 15-44% of cases it was possible to avoid the
renal masses (SRM), defined as solid masses with contrast surgical treatment for a benign pathology (2). Even in case of
enhancement and of size smaller than 4 cm, potentially non-diagnostic biopsy, the repetition is recommended for the
malignant (1). The problem is that such lesions may be benign high effectiveness and low complications rate (3). The only
or with a low aggressive potential, therefore a histological limitation of the studies here documented is that they are not
analysis would be useful aiming at reducing the risk of an based on common and standardized criteria because they are
invasive surgical treatment, especially on elderly patients or leveraging on retrospective experience of different clinical
with serious comorbilities. For this reason, over the last years centers. Conclusion: SRM biopsy is a safe, effective, easily
the role of renal biopsy has increased in importance as an reproducible procedure with high clinical interest. The data
effective method to diagnose SRMs and for the definition of gathered in our experience, even though exiguous, confirm
the correct therapy. Materials and Methods: Between January what documented in literature but further studies are needed
2009 and January 2012, 16 patients (average age: 59) with to confirm the actual utility in the clinical practice.
incidental US diagnosis, then confirmed by CT scan to be of
average size of 3.4 cm (range 2.8-4.0 cm), underwent US- 1 Volpe A, Panzarella T, Rendon RA, Haider MA, Kondylis
guided percutaneous biopsy; among those one with FI and Jewett MA: The natural history of incidentally
transplanted kidney. The test has been run on day-surgery detected small renal masses. Cancer 100: 738-745, 2004.
mode, local anesthesia, with the patient lying prone or on the 2 Volpe A, Mattar K, Finelli A, Kachura JR, Evans AJ, Geddie
side in function of the lesion’s position, using a 16 G needle WR et al: Contemporary results of percutaneous biopsy of
biopsy gun, with coaxial US guide (Toshiba Aplio). The 100 small renal masses: a single center experience. J Urol
average number of cores was 3, with average length of 0.8 cm. 180(6): 2333-2337, 2008.
The average duration of the test was 20 minutes. Each 3 Leveridge MJ, Finelli A, Kachura JR, Evans A, Chung H,
procedure was executed by a single, expert operator who, after Shiff DA, Fernandes K and Jewett MAS: Outcomes of small
the biopsy, also verified via microscope the presence of renal renal mass needle core biopsy, nondiagnostic percutaneous
tissue. After an observation period of 24 hours the patients biopsy, and the role of repeat biopsy. Eur Urol 60: 578-584,
were discharged. Results: In 11 patients the biopsy resulted 2011.
RCC positive; in 2 patients it resulted non diagnostic, then one
of the two repeated the test and resulted positive. One of the
patients with positive biopsy is now awaiting surgery 37
treatment. The patient with RCC on the transplanted kidney CASE OF SPERMATIC CORD AND
has been subjected to mass cryo-ablation. No major TESTICLE ANGIOMYOLIPOMA
complications have been observed but high fever in one
Roberto Giulianelli, Luca Albanesi, Francesco Attisani,
patient, resolved with adequate therapy within 24 hours after
Barbara Crisitna Gentile, Luca Mavilla, Gabriella Mirabile,
the test. One RCC positive patient deceased for intercurrent
Stefano Brunori, Francesco Pisanti, Teuta Shestani,
pathologies. 5 patients have been subjected to VLAP
Giorgio Vincenti, Manlio Schettini
nefrectomy for unfeasibility of the nephron sparing surgery
treatment, and 5 to VLAP partial nefrectomy. The histological Clinica Urologica Villa Tiberia, Roma, Italy
analysis proved the presence of RCC in all the patients who
underwent radical surgery (3 pT1aG1 + 1 G4 sarcomatoid Introduction: The angiomyolipoma (AML or Amartoma) is a
tumor), whereas only 4 patients who underwent conservative mesenchymal tumour, in most cases a benign one, consisting
surgery were diagnosed with RCC (pT1aG1). The patient of differentiated cells in their correct location but forming a
subjected to non-diagnostic biopsy was diagnosed with disorganised mass. It is composed of varying proportions of
angiomyolipoma. The execution of the biopsy test did not vascular cells, immature smooth muscle cells and fat cells. Its
cause complications during the surgical treatment. The median incidence in general population is about 0.3 and 7%. AML are
follow-up time was 15 months, during which no seeding- typically found in the kidney and are strongly associated with
correlated relapsed cancers have been observed. Discussion: a genetic disease, Tuberous Sclerosisi (1). There are some rare
The increase in SRM incidence made the percutaneous biopsy cases of angiomyolipoma observed in different anatomic sites,
become more widespread with a consequent impact on the that makes more difficult the differential diagnosis with
therapy definition: avoidance of surgery in case of benign malignant neoplasia. In literature there are only two cases of
lesions or use of a conservative surgical treatment or even testicle angiomyolipoma described (2, 3). The present is the
adoption of a surveillance therapy. In literature a sensitivity of third case described. The patient was 53 years old, suffering
70-100% and a specificity of 100% are documented, with a of motor deficit due to congenital brain disease. He had
low complications rate (seeding <0.01%, bleeding <1%) and a hypertension in therapy. He reported, in March, the appearence

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

of a sudden testicular pain. The blood tests were normal, symmetric (6). Reported prevalence range is from 0.6 to 9%.
except for white cells (12,65 h/mm3). At the examination the The condition is often associated with germ cell tumor (GCT)
left testis and epididymis were harder and painfull at or intratubular germ cell neoplasia. To our opinion, radical
palpation. Scrotum Ultrasound showed bilateral scattered orchiectomy is still the best therapeutic approach.
microcalcifications. Variation change of structure of the head
of left epididymis, which appeared hypoechoic and encreased 1 Nelson CP and Sanda MG: Contemporary diagnosis and
in volume in comparison with the opposite side, was observed management of renal angiomyolipoma. J Urol 168: 1315-
vascularization bilaterally was preserved. An antibiotic 1325, 2002.
(Rocefin 1 fl im/die) and anti-inflammatory therapy was 2 Lane TM, Masood J, Shah N, Koye B and Hill J:
prescribed. After two weeks, since the symptoms did not Angiomyolipoma of the testis. J Urol 171: 794, 2004.
completely disappear, the patient underwent to a new 3 Saito M, Yuasa T, Nanjo H, Tsuchiya N, Satoh S and
ultrasound evaluation at another clinic. Scrotum Ultrasound: Habuchi T: A case of testicular angiomyolipoma. Int J Urol
right testicle normal for place, shape, size, aberrant ultrasound 15: 185-187, 2008.
structure for the presence of micro-calcifications of 1-2 mm 4 Mues AC, Palacios JM, Haramis G, Casazza C, Badani K,
size. Left testicle roundish, 38×03×30 mm. The tissue Gupta M, McKiernan J, Benson MC and Landman J:
appeared abnormal for the presence of several calcifications Contemporary experience in the menagment of
(1-3 mm). Left epididymis normal for size but hypoechoic as Angiomyolipoma. J Endourol 2010 Oct 2004.
for inflammation status. Light left pampinoform venous plexus 5 Doherty FJ, Mullins TL, Sant GR, Drinwater MA and Ucci
dilatation was present. At this point the patient underwent a AA: Testicular microlithiasis a unique sonographic
surgical exploration of left testicle by inguinal approach which appearance. J Ultrasound Med 6: 389-392, 1987.
ended in orchiectomy. Gross examination showed a soft 6 Otie U, Webb J AW, Oliver RTD, Badenoch DF and Nargund
brownish mass, measuring 4×3×3 cm, replacing the most of VH: Testicular microlithiasis: Is it a benign condition with
the testicular parenchyma, with widespread haemorrhagic malignant potential? Eur Urol 40: 538-542, 2001.
appearance of the cut surface and well circumscribed margins.
Microscopic examination showed medium-to-large calibre
thick-walled blood vessels with ectatic lumina, surrounded by 38
sclerotic fibrous strands and interlacing smooth muscle BIPOLAR TURBT NARROW BAND IMAGING (NBI)
bundles in a fatty context. The peripheral narrow zone of ASSISTED. DOES IT IMPROVE DETECTION AND
residual parenchyma displayed diffuse necrotic and RE-TREATMENT RATES? PRELIMINARY
haemorrhagic infarction of the seminiferous tubules, interstitial EXPERIENCE IN A SINGLE CENTRE
xantogranulomatous flogistic infiltrate with scattered
Roberto Giulianelli, Luca Albanesi, Francesco Attisani,
siderophages and blood cells extravasation. Tunica albuginea
Stefano Brunori, Barbara Cristina Gentile, Luca Mavilla,
was irregularly thickened, epididymis globally preserved.
Gabriella Mirabile, Francesco Pisanti, Teuta Shestani,
Immunohistochemical staining was performed to assay CD34
Giorgio Vincenti, Manlio Schettini
positivity of the blood vessels, SMA positivity of the smooth
muscle fibers and negativity of S100 and HMB-45 stains. Clinica Urologica Villa Tiberia, Roma, Italy
Discussion: Given the rarity of the case, this neoplasia is not
part of the approved list of histology of testicular tumors. This Introduction: Narrow Banding Imaging (NBI) was developed
implies that the diagnosis and eventually treatment have never with the goal of enhancing the definition of small lesions of
been standardized (4). Most of the angiomyolipomas are the bladder that could be missed during White Light
benign but there are cases of renal and extrarenal malignant Endoscopy. The aim of this study was to evaluate the efficacy
angiomyolipomas. Pathologic and immunohistochemical to identify non-muscle invasive bladder cancer by comparing
features of our case as well as the case reported by Saito et al. the predictive power of the white light cystoscopy versus NBI
(3), are indicative for benign testicular angiomyolipoma from cystoscopy and white light endoscopic resection versus the
non-germinal cells. Clinical and ultrasound features make the NBI one. Patients and Methods: From June 2010 to June
differential diagnosis of malignant tesicular tumors very 2011, 482 patients, 301 male and 181 female, affected by non-
diffcult. Our case of angiomyolipoma is the first case in which muscle invasive bladder, underwent NBI Bipolar TURBT.
the tumor is not identifiable by ultrasound as a solid Histological findings are shown in the table below.
intratesticular mass, but associated to testicular microlithiasis,
uncommon condition characterized by calcium deposits within Neoplasms Pumnpl Ta T1
the seminiferous tubules. This condition was first described by
Primitive neoplasms 49 159 74
Doherty et al. (5), on ultrasound, seen as multiple, uniform,
Recurrence neoplasms 30 115 55
nonshadowing echogenic foci of 1-3 mm, usually bilaterally

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The average age was 67.7 yrs. (range 46-88). All patients 39
underwent preoperative white light cystoscopy: topography THE PREDICTIVE ROLE OF NBI RE-TURB IN
and characterization of neoplasms and/or suspicious lesions THE EVALUATION OF T1HG BLADDER
followed by a similar evaluation using NBI. Then all the NEOPLASM RECURRENCE AND PROGRESSION
patients underwent resection of the previously identified RATE. PRELIMINARY EXPERIENCE
lesions performed at first using white light followed by NBI
Roberto Giulianelli, Luca Albanesi, Francesco Attisani,
resection of the bed and surgical margins. All the removed
Stefano Brunori, Barbara Crisitna Gentile, Luca Mavilla,
tissue send separately for histological evaluation after mapping
Gabriella Mirabile, Francesco Pisanti, Teuta Shestani,
the areas of resection on a topographic sheet. All lesions of
Giorgio Vincenti, Manlio Schettini
the lateral side walls were resected after preoperative
additional anesthesia (obturator ipsilateral nerve block). Clinica Urologica Villa Tiberia, Roma, Italy
Follow-up was carried out according to the EAU Guidelines
for non-muscle invasive bladder tumors. Results: The use of Introduction: High grade bladder neoplasia (T1HG TCC)
NBI cystoscopy revealed a total of 325 patients (67.4%) represent a true therapeutic challenge because of a 20-30%
affected by white light non-visible lesions, but only in 200 risk of progression. Sometimes a restaging TURBt better
patients (41.4%), the histological findings showed neoplasms predicts early stage progression. Small or flat cancerous
of the bladder. Overall, with the use of NBI cystoscopy and lesions of the bladder surface may be missed during white
NBI TURBt, we identified 125 (25.9%) benign lesions (i.e., light imaging (WLI) cystoscopy. Different optical imaging
chronic inflammation, reactive urothelial hyperplasia). In the techniques have been developed in an effort to minimize this
T1HG primitive bladder neoplasms group we observed a failure. We investigated whether narrow band imaging (NBI)
40.2% (29/72 pts) cases free of disease, a relapse rate of could improve the detection during follow-up of high-grade
59.7% (43/72 pts), and a progression rate of 14% (10/72 pts). disease recurrence and progression rate (T1HG bladder
The table below shows the detailed results. neoplasm). Patients and Methods: From 6/2010 to 6/2011 a
cohort of 276 patients presenting primary bladder neoplasms
underwent TURBt with Bipolar Surgimaster Scalpel in saline
T Neoplasms Cystoscopy Cystoscopy TURBT TURBT
(TURis); out of this number 72 (26,1%) were T1HG. After a
(pts) WL NBI WL NBI
month HG cancer patients underwent re-TURBT of the
PUNMPL (pts) 31 72 17 58 previously resected area using NBI light to better characterize
Ta (pts) 208 165 201 70 the “bottom of resection” and surgical margins: the aim was
T1 (pts) 77 88 64 72 to evaluate, more precisely, recurrence and progression free
Primitive PUNMPL (pts) 21 40 9 38 survival time. The subsequent follow-up consisted of NBI
Primitive Ta (pts) 115 78 108 49 cystoscopy with multiple biopsies, (randomly and in the
Primitive T1 (pts) 49 37 43 29
previous zone of resection) every 3 months, urinary
Recurrent PUNMPL (pts) 10 22 8 20
Recurrent Ta (pts) 93 87 93 21
oncocytology on 3 specimens and kidney/bladder ultrasound
Recurrent T1 (pts) 28 51 21 43 every 6 months. The average follow-up was 12 (6-18) months.
Results: The T1HG cancer group showed a 40.2% (29/72 pts)
free of disease, a relapse rate of 59.7% (43/72 pts) and a
progression rate of 13.8% (10/72 pts). After NBI re-TURB we
Mean post-surgical hospitalization and catheterization periods found an overall persistence of TCC in 31 (43.1%) cases: 23
were, respectively, 36 and 12 hours; besides mean post (31.9%) high grade (HG) non muscle invasive disease and 8
surgical Hb value was 14.8 gr/dl. No pts. were submitted to (11.1%) high grade (HG) muscle invasive bladder cancer
haemotrasfusion. Early adverse events (EAs) included dysuria (T2HG). In the recurrence group (31 pts) 21 pts (29.1%)
in 27.6% (133 pts.), urgency in 21.6% (104 pts.), haematuria underwent WLI TURBt, while the remaining 10 (13.8%) NBI
in 21.4% (104 pts) and AUR with re-catheterization for clots resection (located in the bed of resection in 2 cases (2.7%) and
in 10.4% (50 pts). Conclusion: Despite the high rate of NBI in surgical margins in 5 (6.9%)). Patients with a high grade
false positives lesions (over 25%), the combination of white (HG) muscle invasion disease (T2HG) were 6 (8.3%): 2
light and NBI appears to allow a better diagnostic and recurrences in the bed and 4 in the surgical margins related to
therapeutic approach of bladder tumours, especially in T1 NBI re-TURBt but only 2 (2.7%) in WL re-TURBT. We
lesions. The high rate of false positives could depend on observed disease progression in 2 patients after 6 and 12
artifacts produced during white light endoscopy. However, months respectively. In the group of 41 (56.9%) patients T0,
NBI TURBt in overall T1HG superficial disease patients the NBI and WL reTURB showed a recurrence in 12 pts
identifies subjects with high rate of early progression (41.9%), (16.6%) and a progression in just 2 (2.7%) who presented a
who need an immediate radical surgical treatment. recurrence after 3 months, associated with CIS. The

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multivariate analysis showed that the most important variable developing of a HG upper urinary tract cancer. Conclusion:
of early progression was the histopathological findings at re- Bladder PUNLMP can occur either as a de novo lesion or
TURBt (p=0.01) followed by the results of the NBI re-TURBt during surveillance for prior higher grade urinary bladder
(p=0.001), presence of CIS (p=0.02) and absence of urothelial neoplasm. None of our PrimaryPUNLMP pts
recurrence within 3 months (p=0.02). Conclusion: NBI re- developed invasive carcinoma or died because of the disease
TURBt in T1HG patients identifies subjects with high risk of despite a 66% recurrence and 43.5% grade progression rates.
early progression disease who need an immediate radical Surveillance PUNLMP was associated with a worse outcome
surgical treatment (early cystectomy). (27.8% grade/stage progression, 3.27% deaths because of
disease progression) most likely due to their initial higher
grade/stage urothelial neoplasm.
40
PAPILLARY UROTHELIAL NEOPLASM
OF LOW MALIGNANT POTENTIAL (PUNLMP): 41
OUR LONG TERM EXPERIENCE URINARY DIVERSION CHOICE AFTER
PELVIC EXENTERATION FOR RECURRENT
Roberto Giulianelli, Luca Albanesi, Francesco Attisani,
CERVICAL CANCER: SINGLE INSTITUTION
Stefano Brunori, Barbara Crisitna Gentile, Luca Mavilla,
13 YEARS EXPERIENCE
Gabriella Mirabile, Francesco Pisanti, Teuta Shestani,
Giorgio Vincenti, Manlio Schettin Deliu Victor Matei1, Sara Melegari1, Giacomo Galasso1,
Giovanni Cordima1, Antonio Brescia1, Danilo Bottero1,
Clinica Urologica Villa Tiberia, Roma, Italy
Fabio Landoni2, Angelo Maggioni2, Ottavio De Cobelli1
Introduction: The present study evaluates behavior of de-novo 1Urologia, Istituto Europeo Oncologico, Milano;
primary bladder PUNLMP lesions (Primary-PUNLMP) as 2Ginecologia, Istituto Europeo Oncologico, Milano, Italy
well as Surveillance-PUNLMP (diagnosed during follow-up
of a higher grade urothelial neoplasm. Patients and Methods: Introduction: Pelvic exenteration (PE) was initially utilized for
From January 2006 to June 2011, 608 patients (Males=430, the palliative surgical management of recurrent gynecologic
Female=178; mean age 71.8+9.2 years) underwent cancers, then it evolved into a curative intervention for
transurethral resection (TURBT) of all visible tumours. We advanced and recurrent gynecologic cancers confined to the
retrospectively analysed our TURBT database and identified central pelvis. Its exenterative time is characterized by pelvic
all patients with a histological examination revealed a viscera removal and blood vessels ligation, often difficult
PUNLMP lesion type. Results: We identified a total a 61 because of previous surgery and radiotherapy, and a
PUNLMP of the bladder; 22 (36.07%) pts categorized as reconstructive phase that needs multidisciplinary approach.
Primary-PUNLMP and remaining 39 (63.93%) pts as The aim of this study was to compare urologic complication in
Surveillance-PUNLMP. During follow-up, 36 mo. (range: 6- patients with Indiana pouch(IP) versus ileal conduit (IC) as
66 mo), in the Primary-PUNLMP group, 12/22 (54.5%) urinary diversion after pelvic anterior or total exenteration for
patients did not develop any recurrences vs. 13/39 (33.3%) in recurrent cervical cancer. Patients and Methods: From 1997
the Surveillance-PUNLMP group. In the first group, 4/22 to 2011 at IEO 151 PE were performed, 83 PE for cervical
(18,8%) pts developed PUNLMP recurrence (1-2 episodes in cancer. In our series 54% of women presented with a
1-4 yrs) and 7/22 (31.8%) progression to a higher grade persistent disease, 38% had a recurrence, 8% recurrence
lesions within 1-4 yrs. Grade progression was non invasive persistence after neoadjuvant chemotherapy; 60% had a
low grade urothelial carcinoma (LG-TCC) in 6 pts (27.2%) central pattern of recurrence, while 40% a lateral one. 40
and non invasive high grade urothelial carcinoma (HG-TCC) underwent anterior PE and 43 total PE. 39 women received an
in 1 pts (4.5%). None of our Primary-PUNLMP pts developed IC as urinary diversion, and 44 received an IP. 43 needed a
muscle-invasive carcinoma or died because of disease colostomy. Results: In our series overall 5 years survival for
progression. Tumour size did not correlate with likelihood for cervical cancer was 48% versus 80% in patients receiving an
recurrence. In the second group, 26/39 pts (66.6%) showed urinary diversion for transitional cells tumor. Overall the time
PUNLMP during surveillance for higher grade urinary to the first complication was 1.33 years. According to urinary
bladder’s lesions. These included 16 (41.02%) prior LG-TCC, diversion overall survival was longer for having undergone IP
9 (23.07%) prior HG-TCC and 1 (2.56%) found in cystectomy versus IC, but survival free of complications was higher for
for invasive neoplasm in bladder diverticula. Grade IC with a mean time to the first complication of 2.1 years
progression to LG-TCC was in 11 pts (28.2%) while versus 0.8 years of IC (p=0.06). As far as urinary diversion
progression to HG-TCC in 6 (15.3%). Two patients (5.12%) related complication is concerned a total of 45 (54.2%)
died in HG-TCC group and one (2.56%) in the LG-TCC after women experienced a complication, 28 (65.1%) of IP and 17

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

(43.6%) of IC. In particular 38 (24 vs. 14) patients had 5Oncologia Medica a Direzione Universitaria Fondazione del
hydronephrosis, 8 (4 vs. 4) had U-I leakage, 1 had a pouch Piemonte per l’Oncologia, Istituto per la ricerca e Cura del
leak, 4 (2 vs. 2) had a urostoma stenosis, 1 IC patient had a Cancro Candiolo, TO, Italy
renal abcess and 2 IP formed stones. Overall 7 patients
experienced 2 urinary diversion related complications and 3 Background: The purpose of this study was to investigate the
more than 2. According to Clavien classification 23.6% of safety and efficacy of mTOR inhibitors (temsirolimus and
these were Clavien I, 43.6% were Clavien IIIa (needing often everolimus) in patients with metastatic renal cell carcinoma
the intervention of radiologist), 20% were Clavien IIIb and (mRCC) and end-stage renal disease requiring haemodialysis
12.7 % were Clavien IVa. Considering the occurrence of (HD). Renal function plays a crucial role in drug treatments: if
hydronephrosis and comparing IEO gynecologic series (39 IC renal excretion is significantly reduced, the drug will be
vs. 44 IP) with IEO urologic series (190 IC vs. 115 eliminated more slowly and the risk of toxicity will increase
neobladder) we noted that hydronephrosis occurred in 45.7% proportionally to the increased blood concentration of the
of gynecologic group (35.9 % vs. 54.5 %) vs. 8.2% of urologic drug. For these reasons, the treatment of patients with cancer
group (9.5% vs. 7.3%), even if it occurred earlier in urologic receiving dialysis, is a problem for medical oncologists. A few
group (11.8 months versus 19.08 months). Other urinary- published data indicating that the use of TKIs (sunitinib and
related complications owned to IP: 3 urinary leak and 18 sorafenib) is feasible in this subgroup of patients, with no
(42%) metabolic acidosis requiring medication (mean Na unexpected toxicity and a good efficacy, are currently available
bicarbonate supplementary intake: 2g/d). DISCUSSION 35% (1). The pharmacokinetics of temsirolimus has been studied
of all CC treated will experience recurrent or persistent only in case series including patients receiving hemodialysis:
disease. The rate of recurrence depends on the disease FIGO the study found that after a single dose of 25 mg of
staging, lymph node involvement, surgical margins, tumor size temsirolimus as a 30-minute intravenous infusion, neither
and deep infiltration. Younger age, better survival expectancy temsirolimus nor sirolimus concentrations were significantly
(small [<5 cm] central recurrence), and good hand dexterity affected in those mRCC patients receiving HD as compared
should push the choice towards a continent diversion. Surgery to those not receiving HD (2). Patients and Methods: Between
radicality quieries (the need to remove from 2/3 to all the December 2008 and February 2012, 8 patients undergoing HD
vagina or infraelevator PE) determine the impossibility to were treated with temsirolimus and everolimus for mRCC in
create an orthotopic ileobladder. The risk of complications and five Italian Institutions. We retrospectively reviewed the
QoL studies are important factors to take into account when medical records of these patients to evaluate the administered
urinary diversion is chosen. CONCLUSION There are no doses of mTOR inihibitors, treatment related toxicities and the
guide lines about urinary diversion choice in cervical cancer; clinical response. Results: Five patients were males, the
literature is insufficient to conclude that a urinary diversion is median age was 64 years (range 47-79), 7/8 patients had a
superior to another considering HRQOL outcomes. In our clear cell histology. All patients were receiving HD, 4/8 pts
series overall survival is longer for IP versus IC, but survival for bilateral nephrectomy and others for previous chronic renal
free of complications is better for IC. disease and the time interval between the start of HD and the
start of mTOR inhibitors treatment was 37 months. According
to Motzer’s criteria, six patients were classified as good and
42 intermediate risk. Everolimus was administered at 10 mg with
TREATMENT OF HEMODIALYZED a continuous schedule in five patients; three patients received
PATIENTS WITH METASTATIC RENAL CELL temsirolimus at 25 mg as a 30-minute intravenous infusion
CARCINOMA WITH MTOR INHIBITORS weekly. Two patients received temsirolimus as first-line
treatment, one patient as third-line; three patients received
Cristina Masini1, Alessandra Felici2, Giuseppe Di Lorenzo3,
everolimus as second-line treatment, one as third-line and one
Azzurra Onofri4, Veronica Prati5, Pasquale Mighali1,
as fourth-line. With regard to tolerability and safety, no
Pier Franco Conte1, Roberto Sabbatini1
unexpected adverse event (AE) was registered and no grade 4
1Dipartimento di Oncologia, Ematologia e Malattie haematological or non-haematological toxicity was reported.
dell’Apparato Respiratorio Azienda Policlinico-Universitaria The most common grade 1-2 nonhaematological treatment-
di Modena; related AEs were fatigue (5/8 patients), dyslipidemia (4/8
2Divisione di Oncologia Medica A Istituto Nazionale Tumori patients), dyspnea (2/8 patients) and hyperglycemia in one
Regina Elena, Roma; case. A grade 3 cutaneous rash was observed in one patient
3Department of Endocrinology and Medical Oncology, treated with everolimus. The most frequent grade 1-2
Genitourinary Cancer Section University Federico II, Napoli, haematologic toxicity was anemia (5/8 patients). None of
4Clinica di Oncologia Medica AO, Ospedali Riuniti, these toxicities led to discontinuation of the treatment.
Università Politecnica delle Marche, Ancona; Temsirolimus and everolimus were administrated at any time

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

regardless of the timing of HD. Among these 8 patients treated symptoms related to the lymphocele and underwent
with mTOR inhibitors, stable disease was observed in 5 percutaneous US or CT scan guidance drainage. The drainage
patients. At the time of the analysis, 2 patients had died due was maintained for a mean time of 24 days (7-46 days) 15%
to disease progression. The estimated median progression-free of lymphoceles were bilateral. According to the higher
survival of this cohort of patients was 6.3 months. Discussion diameter 4,7 % of lymphoceles were <4 cm, 76.2% were 4-10
and Conclusion: In this small retrospective series of patients cm, and 18.1% were >10 cm respectively. On the logistic
with mRCC undergoing hemodialysis during mTOR inhibitors regression model the presence of nodal metastases (8 %
treatment, the incidence of adverse events was acceptable, and versus 15%) was significantly higher if the limphocele
a prolonged progression free survival was observed. The use occurred, while the number of removed lymph nodes (mean
of temsirolimus and everolimus does not seem to be 11.61 versus mean 13,55) didn’t reached the statistical
contraindicated in patients with mRCC receiving HD. significance (p=0.06); if only the symptomatic lymphocele
patients were considered, the number of removed lymph
1 Masini C, Sabbatini R, Porta C et al: Use of tyrosine kinase nodes (mean 14.52 lymph nodes) was significantly higher
inhibitors in patients with metastatic kidney cancer receiving (p<0.01) if compared with the patients without lymphocele.
haemodialysis: a retrospective Italian [Link] Int. 2012 Tumor stage >pT3 was also predictive for the development of
Feb 24. doi: 10.1111/j.1464-410X.2012.10946.x. [Epub lymphocele: 67.5% vs. 51.8% (p<0.01). Discussion: The
ahead of print]. occurrence of lymphocele is one of the most frequent
2 Lunardi G, Armirotti A, Nicodemo M et al: Comparison of complications after robot assisted radical prostatectomy. The
temsirolimus pharmacokinetics in patients with renal cell rate of delectability depends on the method of screening for
carcinoma not receiving dialysis and those receiving lymphocele occurrence: systematic or spontaneous. If
hemodialysis: a case series. Clin Ther 31(8): 1812-1819, symptomatic, it may require percutaneous drainage or even
2009. laparoscopic unroofment. Higher number of removed LN, the
presence of LN metastasis and extracapsular disease are
significantly higher in the subgroup of patients having
43 undergone LND and having successively experienced
INCIDENCE AND RISK FACTORS lymphocele occurrence. Tomic et al. showed that the
OF LYMPHOCELE OF PELVIC incidence of lymphoceles in patients who had received
LYMPHADENECTOMY DURING ROBOT subcutaneous low-dose heparin is higher if compared with
ASSISTED RADICAL PROSTATECTOMY controls. The use of clips or ligatures for ligation of lymph
channels is associated with less lymphocele formation if
Deliu Victor Matei1, Sara Melegari1, Federica Mazzoleni1,
compared to the use of fibrin sealant agents. Our study
Serena Detti1, Ioan Coman2, Nicolae Crisan2,
confirms Patel’s observations that SV involvement, EC
Ottavio De Cobelli1
disease and nodal involvement are predictors of lymphocele
1Urologia Istituto Europeo Oncologico, Milano, Italy; occurrence risk in patients undergoing LND. The role of the
2Urologia Spitalul Municipal Cluj Napoca Romania extension of LND template in increasing the lymphocele risk
is debatable as contrasting data are reported in the literature.
Objective: The aim of this study was to determine the In our study, the number of removed LN was significantly
incidence and to evaluate the presence of predictive factors higher only in symptomatic patients. Conclusion: Our data
of lymphocele development in patients undergone pelvic show that pelvic lymph node dissection is associated with a
lymph node dissection (PLND) during robot-assisted radical quite high rate of lymphocele formation. In our experience
prostatectomy (RARP). Patients and Methods: From 1st percutaneous US or CT-scan guidance drainage represents the
November 2006 to 31st December 2011 we performed 1032 choice treatment of symptomatic patients.
robot assisted radical prostatectomies for prostate cancer.
Lymphadenectomy was performed if the risk of lymph node 1 Tomic R, Granfors T, Sjodin JG and Ohberg L: Lymph node
involvement, according to the MSKCC (Sloan Kettering) leakage after staging pelvic lymphadenectomy for prostatic
nomogram, was >4%. 366 patients with a follow-up >3mos, carcinoma with and without heparin prophylaxis. Scand J
having received standard LND, were considered. All patients Urol Nephrol 28(3): 273-275, 1994.
received subcutaneous low-dose heparin prophylaxis. Bipolar 2 Naselli A, Andreatta R, Introini C, Fontana V and Puppo P:
forceps, monopolar scissors and Weck clips were used during Predictor of symptomatic lymphocele after lymph node
LND. Results: The mean follow-up was 25 months. 42 excision and radical prostatectomy. Urology 75: 630, 2010.
patients (11.47%) presented lymphocele at a mean of 61 days 3 Orvieto MA, Coelho RF, Chauhan S, Palmer KJ, Rocco B
(18-168 days) from surgery: 19 (5.19%) were a- or and Patel VR: Incidence of lymphoceles after robot assisted
paucisymptomatic while 23 (6.28%) patients presented with pelvic lymph node dissection. BJUI 108: 1185-1190, 2011.

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44 PRIMARY CELL CULTURES OF

RISK OF OVERTREATMENT IN CLINICALLY HUMAN PROSTATE CARCINOMA
NOT SIGNIFICANT PROSTATE CANCER:
Alessandro Sciarra, Stefano Salciccia, Francesco Minisola,
SINGLE CENTRE EXPERIENCE
Alessandro Gentilucci, Andrea Alfarone, Susanna Cattarino,
Giandavide Cova, Claudio Lamon, Francesco Beniamin, Michele Innocenzi, Michele Ravaziol, Giuseppina Ippoliti,
Giovanni Luca Drago Ferrante, Luigino Maccatrozzo Vincenzo Gentile
Urologia Ospedale Ca Foncello Treviso, Italy Dipartimento di Urologia [Link] Policlinico Umberto I,
Roma, Italy
Aim: Clinically insignificant prostate cancer defined as cT1c
stage, Gleason score ≤6, PSA ≤10 ng/ml, and tumor volume Introduction and Objectives: The aim of our study was to
≤0.5 mm is characterized by limited biologic malignancy and, analyze and to compare the expression of the inflammatory
possibly, suitable for non-radical treatment. The purpose of the pathways and the proliferative-apoptotic indexes either in
study was to perform a retrospective analysis of the outcome classic human Prostate Cancer (PC) cell lines, such as
of patients with clinically insignificant prostate cancer who androgen-dependent LnCap and androgen-independent PC3
underwent radical prostatectomy in order to assess the cell lines or also in primary cultures of human prostate
predictors of cancer-related outcome. Patients and Methods: adenocarcinoma cells. On these different settings, we
From January 2004 to February 2012 we performed 1066 evaluated the effect of LSESr (Permixon) on the inflammatory
retropubic radical prostatectomies. Among these patients, 124 factors, analyzing whether its possible antiinflammatory
(12%) had a clinically insignificant prostate cancer, according activity determines an effect on proliferation and apoptosis.
to the biopsy criteria. Biopsy and specimen Gleason score, Materials and Methods: We homogeneously analysed the
prostate biopsy sampling (standard vs. saturation), pathological mRNA expression of several genes related to inflammation:IL-
stage, extraprostatic involvement and surgical margin status 6,CCL-5(RANTES),CCL-2,COX-1,COX-2,iNOS in LnCaP
were evaluated. During follow-up, patients had semiannually and PC3 cell lines and primary cultures obtained from 40
PSA sample and clinical evaluation. Results: 102 patients patients undergoing radical prostatectomy for PC. From each
(82%) had clinically significant prostate cancer in the case, we processed tissue fragments either from PC nodules
prostatectomy specimen, with 82% of the patients having (named Tumor “T”) or from normal tissue (named control
organ-confined disease. Gleason score was 6 in 68% of the “Ct”). Moreover all cultures (PC3,LNCaP and primary
cases. Surgical margins were positive in 22 cases (18%) and cultures) were treated with LSESr (Permixon) at
extraprostatic involvement occurred in 21 cases (17%). concentrations of 44 and 88 μg/ml and we observed the effect
Concordance among biopsy and specimen Gleason score was of this drug on the expression of inflammatory-related genes
limited, with clinical undergrading occurring in 52 cases and on cell growth, analysing the proliferation and apoptotic
(42%), regardless of the biopsy scheme. The median follow-up indexes, at different time periods of incubation (24, 48 and 72
duration was 52 months. At follow-up, extraprostatic extension hours). Finally, we analysed Nf-kB gene expression by
and surgical margin status were independent predictors of immunofluorescence in PC3 cell line in untreated and treated
biochemical recurrence-free survival (p=0.008). Discussion: conditions. Results: The first result was that in all cultures
The risk of overtreatment ranges from 0 to 48% according to (PC3, LNCaP and primary cultures) all these inflammatory-
Literature data. To date, we do not have major variables related genes were expressed and all were down-regulated by
predictive of clinically insignificant prostate cancer. In our LSESr. The second result obtained (LNCaP,PC3 and primary
experience, only 18% of the patients undergoing radical cultures) indicated a significant reduction in PC and normal
prostatectomy for clinically insignificant prostate cancer had cell counting related to LSESr treatment. Finally, we detected
clinically insignificant cancer in the prostatectomy specimen, an induction of apoptotic pathway suggested by the caspase-3
whereas in 17% of the cases we found a high risk disease. activation and an induced activation of Nf-kB through its
Conclusion: Low risk prostate cancer does exist. However, translocation in the cell nucleus after treatment with LSESr.
predictive variables able to identify appropriately such patients Conclusion: The present study confirmed the role of
are lacking. The risk of overtreatment is present but currently inflammation in prostate carcinogenesis. For the first time in
counterbalanced by the risk of undertreatment. literature we showed the effect of LSESr on down-regulation
of inflammatory-related genes in cell lines and in primary
cultures and we showed that the inhibitory effect of LSESr
45 (Permixon) on cell growth could be at least in part associated
EFFECT OF SERENOA REPENS ON to the down-regulation of inflammatory-related genes and to
THE EXPRESSION OF THE the activation of Nf-kB pathway, as well as a pro-death
INFLAMMATORY PATTERN IN response in prostate tissue.

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

46 Introduction: Since the eighties the permanent interstitial

MULTIPARAMETRIC MAGNETIC RESONANCE brachytherapy has been more and more utilized for the
IMAGING OF THE PROSTATE CAN IMPROVE treatment of early stage prostate cancer. This has been favored
THE PREDICTIVE VALUE OF URINARY PCA3 by the development of implantation techniques with the aid of
TEST IN PATIENTS WITH ELEVATED PSA transrectal ultrasound and specific software for Treatment
LEVELS AND PRIOR NEGATIVE BIOPSY Planning System (TPS). The aim of the study was to evaluate
medium and long-term therapeutic efficacy of interstitial brach
Alessandro Sciarra, Stefano Salciccia, Francesco Minisola,
therapy in the treatment of localized carcinoma. Patients and
Alessandro Gentilucci, Andrea Alfarone, Susanna Cattarino,
Methods: From March 2001 to January 2012, with a median
Michele Innocenzi, Michele Ravaziol, Giuseppina Ippoliti,
follow-up of 45.6±31.6 months (range 1.5-120.6), 176 patients
Vincenzo Gentile
with a mean age of 71.0 years (range 47-82) underwent
Dipartimento di Urologia U. Bracci Policlinico Umberto I, permanent interstitial brachytherapy with I125 as a primary
Roma, Italy treatment for prostate cancer. After the acquisition of
morphologic and volumetric data of the gland using transrectal
Objectives: To evaluate the role of multiparametric magnetic ultrasound, TPS allowed to define the optimal geometry of
resonance imaging (MRI) as an additional diagnostic tool to seed placement under a dosimetric plan. The needles
improve the accuracy of urinary PCA3 test in patients with preloaded with radioactive seeds were inserted through
PSA increase and previous negative prostate biopsy. Patients transperineal access, with spinal or general anesthesia, using
and Methods: This is a prospective randomized study on ultrasound guide and fluoroscopy. Patients were selected
patients with prior negative TRUS-guided prostate biopsy and according to the instructions of the American Society of
elevated PSA levels; 180 cases were analysed, all submitted Brachyterapy: Stage: T1-T2 Age <80 years PSA <10 ng/ml
to PCA3 assay. Patients in Group A were submitted to a Life expectancy =>10 years; Gleason score <7 Prostate
second random TRUS-guided prostate biopsy,whereas patients volume <50 cc; Qmax>15; MR/CT negative In selected cases
in Group B were submitted to a multiparametric MRI the indication were extended. Results: Median D90 152±27
examination and then to a second TRUS-guided prostate Gy (range 58-217). Currently 122 patients have a follow-up
biopsy. Results: At the second biopsy, a histologic diagnosis longer than 2 years. 105 patients (86.1%) are free from disease
of PC was found in 26 out of 84 cases (30.9%) in Group A or biochemical recurrence. The 5 years disease-free survival
and in 29 out of 84 cases (34.5%) in Group B. In group A was 88.7%. No patient died from prostate cancer. Univariate
sensitivity and specificity of PCA3 score were 68.0% and analysis showed that PSA (p=0.5), Gleason score (p=0.35),
74.5% respectively (PPV of 53.1%, NPV of 84.6% and age (p=0.98) and low D90 (<145 Gy) (p=0.45) are not
accuracy of 72.6%). In Group B sensitivity and specificity of significant prognostic factors with regard to biochemical
PCA3 score were 79.3% and 72.7% respectively (PPV of failure (ASTRO). No patient with D90<100 Gy had
60.5%, NPV of 86.9% and accuracy of 75.0%). For the PCA3 biochemical recurrence. 8 patients (4.5%) developed grade 3
score, the area under the ROC curve (AUC) was 0.825 (95% urinary toxicity and 2 patients (1.1%) developed grade 3 rectal
confidence interval 0.726 to 0.899) in Group A and 0.857 toxicity. Conclusion: Permanent interstitial brachytherapy in
(95% confidence interval 0.763 to 0.924) in Group B selected patients with low risk prostate cancer appears to be
(p<0.0001). Conclusion: In patients with previous negative an effective treatment with results similar to those obtained by
biopsy and persistently elevated PSA levels, the use of radical prostatectomy and external beam radiotherapy.
multiparametric MRI in indicating sites suitable for rebiopsy
can significantly improve the sensitivity of PCA3 test for the 49
diagnosis of PC. CARDIOTOXICITY IN METASTATIC RENAL
CELL CARCINOMA (mRCC) PATIENTS
TREATED WITH SUNITINIB (SU)
48
Valentina Ballatore, Veronica Prati,
PERMANENT INTERSTITIAL BRACHYTHERAPY
Fiorella Ruatta, Danilo Galizia, Giovanni Grignani,
IN THE TREATMENT OF LOCALIZED
Massimo Aglietta, Cinzia Ortega
PROSTATE CANCER: OUR EXPERIENCE
Oncologia Medica Fondazione del Piemonte per
Alfredo Trippitelli1, Alessandro Della Melina1,
L’Oncologia, Istituto per la Ricerca e Cura del Cancro
Stefano Nerozzi1, Giuseppe Canovaro1,
Candiolo, Torino, Italy
Marco Stefanacci2, Roberto Santini2, Luca Bernardi3
1Urology AUSL3 Pistoia, 2Radiotherapy AUSL3 Pistoia, Background: Cardiovascular events (CVE), e.g. CHF
3Physics AUSL3 Pistoia, Italy (congestive heart failure) and coronary artery disease (CAD),

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

may occur in up to 10% of patients (pts) treated with sunitinib renal cell carcinoma. Journal of clinical oncology official
(SU). Cardiovascular monitoring during SU treatment may Journal of the American Society of: Clinical Oncology
underline early signs of myocardial damage. Patients and 26(32): 5204-5212, 2008.
Methods: We have prospectively analyzed pts naïve for 3 Altena R, Perik PJ, van Veldhuisen DJ, de Vries EGE and
therapies with tyrosine kinase inhibitors (TKIs) receiving SU Gietema JA: Cardiovascular toxicity caused by cancer
as a treatment for mRCC. Between April 2007 and December treatment: strategies for early detection. The Lancet
2011, a total of 33 consecutive pts, median age 65 yrs (41-80), Oncology 10(4): 391-399, 2009.
were treated with SU. The median duration treatment was 8.3
months (0.4-22.1). All patients were analyzed for CAD risk
factors (hypertension, hypercholesterolemia, diabetes, 50
smoking), rhythm disturbances and heart failure. ECG, KETOCONAZOLE IN THE TREATMENT OF
echocardiography and cardiology consultation were performed CASTRATION RESISTANT PROSTATE CANCER
at baseline and every three months until progression or SU (CRPC): EFFICACY OF LOW-DOSES
permanent discontinuation. We prospectively recorded the
Fiorella Ruatta1, Veronica Prati1, Valentina Ballatore1,
following pts features: left ventricular ejection fraction (LVEF),
Elisabetta Garibaldi2, Pietro Gabriele2, Giovanni Muto3,
cardiovascular history, blood pressure, antihypertensive therapy.
Massimo Aglietta1, Cinzia Ortega1
For 14/33 pts we also recorded at the same intervals patterns
of mitral valve inflow. We defined cardiotoxicity as a reduction 1Oncologia Medica Fondazione del Piemonte per
of LVEF ≥10%. Results: At baseline LVEF media was 66% l’Oncologia - Istituto per la Ricerca e Cura del Cancro
(85%-55%) which decreased to 61% on SU treatment (77%- Candiolo, Torino;
45%). This reduction was statistically significant (p=0.003). 16 2radioterapia Fondazione del Piemonte per l’Oncologia

out of 33 pts (48,5%) had a reduction of LVEF ≥10% on SU Istituto per la Ricerca e la Cura del Cancro;
treatment. 15 of these 16 pts were asymptomatic and only one 3Urologia Ospedale San Giovanni Bosco, Torino, Italy

showed symptoms of CHF and temporarily discontinued SU

treatment. This patient had a global myocardial hypokinesia at Background: The management of rising PSA in CRPC
echocardiography. At baseline 23 pts (69.7%) had hypertensive remains controversial. Among second-line hormonal therapy
disease (HD) but neither this CAD risk factor nor options ketoconazole, an antimycotic that affects the synthesis
hypercholesterolemia, diabetes and smoking resulted predictive of androgens and other steroids, has shown direct cytotoxic
of cardiotoxicity. On SU therapy 5 out of 23 pts worsened the effects in prostate cancer. This retrospective study describes
preexisting HD which was controlled with adequate medical our experience with low doses of ketoconazole and prednisone
treatment and did not determine a discontinuation of SU treatment for CRPC. Patients and Methods: From 4/2007 to
therapy. Furthermore 7 pts (21.2%) developed this adverse 12/2011, 65 patients with progressive CRPC who were
event. 14/33 pts were also evaluated for diastolic function. At previously treated with maximal androgen blockade received
baseline we recorded 7 pts (50%) with normal mitral valve 200 mg ketoconazole orally bid with orally replacement
inflow pattern and 7 (50%) with impaired left ventricular (LV) prednisone (5 mg bid) and maintained LHRH-agonists.
relaxation. On SU therapy pts with this last pattern did not Performance status of all patients was ECOG0. Overall, 34/65
experience changes, but 6/7 pts (85.7%) with normal pattern at (52.3%) patients had only bone metastases, 12/65 (18.5%) had
baseline developed an impaired LV relaxation pattern. nodal metastases, 17/65 (26.2%) both and only 2/65 (3.1%)
Conclusion: Cardiac damage is often underestimated but it is had bone plus lung metastases. All patients had low tumor
manageable with careful cardiovascular monitoring and burden and PSADT >6 months. Thirty-six out of 53 patients
medical treatment at first signs of myocardial damage. Since with bone metastases received concomitant zoledronic acid.
an early identification and treatment of pts at risk to develop PSA response was defined as a >50% fall in PSA from
CHF may reduce this dreadful event and treatment baseline and PSA nadir was calculated. Progression was
discontinuation, it is important to record CAD risk factors and defined by objective disease progression or PSA increase of
cardiac function at baseline and to monitor cardiac function >50% above nadir or >25% above baseline. Patients were
during SU therapy. Analysis of diastolic function may play a monitored clinically and with serial PSA measurements
useful role in early detection of myocardial damage. every 1-month. Results: Median age was 74.05 (range: 52.8-
84.4) years; median baseline PSA was 29.95 (range: 1.18-
1 Cheng H and Force T: Molecular mechanisms of 1348.8) ng/ml; median duration of the treatment was 5.87
cardiovascular toxicity of targeted cancer therapeutics. (range: 0.57-52.4) months. All pts were evaluable for PSA
Circulation Res 106(1): 21-34, 2010. response. At a median F.U. of 15.4 mos. 19/65 patients
2 Schmidinger M, Zielinski CC, Vogl UM et al: Cardiac (29.2%) showed a decrease in PSA >50%, with a median
toxicity of sunitinib and sorafenib in patients with metastatic TTP of 17.23 mos for responders. Overall TTP was 5.86 mos

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

and it was not affected by metastatic sites (p=0.71). Toxicity 230) and estimated blood loss was 200 mL. Median hospital
was mild and no patients discontinued therapy because of stay was 5 days (3-7). There were no intraoperative
side-effects. Five out of 65 patients had G2 ([Link] 4) complications. 3 patients had postoperative complications
nausea and moderate elevated transaminases. No acute (delayed renal hemorrhage) that required blood transfusions
hepatitis or adrenal insufficiency was observed. Conclusion: but not surgical therapy. In 1 patients final pathological
Our data confirm that low-dose ketoconazole is an effective examinations revealed a positive surgical margin. Pathology
and well-tolerated treatment in patients with CRPC and should confirmed renal cell carcinoma in all cases. Median pre- and
be considered in the subset of patients with low-volume postoperative serum creatinine (0.95 and 1.05 mg/dl) were
disease and a rising PSA level despite maximal androgen similar. Discussion and Conclusion: Our preliminary
blockade. experience with zero-ischemia laparoscopic partial
nephrectomy is encouraging.
1 Harris KA, Weinberg V, Bok RA, Kakefuda M and Small
EJ: Low-dose ketoconazole with replacement doses of 1 Gill IS, Eisenberg MS, Aron M, Berger A, Ukimura O, Patil
hydrocortisone in patients with progressive androgen MB, Campese V, Thangathurai D and Desai MM: Zero
independent prostate cancer. J Urol 168(2): 542-545, 2002. ischemia” partial nephrectomy: novel laparoscopic and
2 Small EJ, Halabi S, Dawson NA, Stadler WM, Rini BI, robotic technique. Eur Urol 59(1):128-134, 2011.
Picus J et al: Antiandrogen withdrawal alone or in 2 Abreu AL, Gill IS and Desai MM: Zero-ischaemia robotic
combination with ketoconazole in androgen-independent partial nephrectomy (RPN) for hilar tumours. BJU Int 108(6
prostate cancer patients: A phase III trial (CALGB 9583). J Pt 2): 948-954, 2011.
Clin Oncol 22(6): 1025-1033, 2004. 3 Patil MB and Gill IS: Zero-ischaemia robotic and
3 Nakabayashi M, Xie W, Regan MM, Jackman DM, Kantoff laparoscopic partial nephrectomy (PN). BJU Int 108(5):
PW and Oh WK: Response to low-dose ketoconazole and 780-92, 2011.
subsequent dose escalation to high-dose ketoconazole in
patients with androgen-independent prostate cancer. Cancer
107(5): 975-981, 2006. 52
4 Fillos TJ, Chu D and Wu S: Efficacy of ketoconazole in ACETYLCHOLINE IS A PROMOTING FACTOR
castration-refractory prostate cancer: A meta-analysis. FOR HUMAN UROTHELIUM? RESULTS
ASCO meeting; Abs no. 199, 2008. OBTAINED IN THE UROTSA CELL LINE
N. Arrighi1, S. Bodei2, A. Lucente2, M.C. Michel3,
D. Zani1, C. Simone1, S. Coscianicunico1,
51
P.F. Spano2, S. Sigala2
ZERO – ISCHEMIA LAPAROSCOPIC PARTIAL
NEPHRECTOMY: PRELIMINARY EXPERIENCE 1Università degli Studi di Brescia Cattedra di Urologia;
2Cattedra Di Farmacologia Università degli Studi di Brescia,
Fabiano Palmieri, Giorgio Bruno, Calogero Di Stefano,
Italy;
Enza Lamanna, Remigio Pernetti, Salvatore Voce 3Department of Pharmacology, J Gutemberg, University,

Dipartimento di Scienze Chirurgiche/Urologia, Ospedale Mainz (D), Collaborating with Boeringer-Ingelheim,

Civile di Ravenna, Italy Germany

Background: Ischemic injury impacts functional outcomes in Introduction: The urothelium is increasingly recognized as a
patients undergone laparoscopic partial nephrectomy. Efforts highly active tissue which responds to various signals and
to reduce ischemia time are necessary to minimize generates and releases mediators contributing importantly to
postoperative renal injury. We evaluated the feasibility and the regulation of bladder function. Specifically, the urothelium
safety of laparoscopic assisted partial nephrectomy without of various species has been shown to contain the necessary
hilar clamping. Patients and Methods: Clinical data were transporters and enzymes for the synthesis of acetylcholine
prospectively collected. Since January 2011, 22 consecutive (ACh) including the vesicular acetylcholine transporter
patients underwent zero ischemia laparoscopic partial (VAChT) and choline acetyltransferase (ChAT). Beside ChAT,
nephrectomy through a retroperitoneal approach. In all cases carnitine acetyltransferase (CarAT), which could also
a sutureless haemostasis was performed. Results: Zero- synthesize ACh, has been found in the mouse and human
ischaemia laparoscopic partial nephrectomy was successfully urothelium. An autocrine and/or paracrine loop of ACh and
completed in all cases. The median tumour size was 3.7 cm muscarinic receptors has been implicated in the remodelling
(range: 2.5-5). Warm ischaemia time was zero in all patients. of tissues other than the bladder and may be associated with
The median operative time was 175 minutes (range: 120- malignant growth. Against this background, we have used

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UROtsa cells, an immortalized cell line derived from normal and mediated by ERK and PI3 kinase pathways pose attention
human urothelium, which is widely used to study human on the role of ACh as a possible cell proliferation promoter in
urothelium physiology and pathophysiology, to investigate 1) different pathological scenarios, either in benign settings as
the presence of the non-neuronal cholinergic muscarinic well as in promoting the progressive cell degeneration giving
system, 2) the signaling of muscarinic receptors and 3) the rise to the urothelial cancer.
involvement of muscarinic subtypes and specific signaling
pathways in urothelial proliferation responses. Materials and 53
Methods: UROtsa cells were cultured in D-MEM IS INVASION OF MUSCULAR
supplemented with 5% fetal bovine serum. Cells were treated LAYER REALLY EFFECTIVE IN
for up to 3 days with different drugs: the agonist carbachol PROGNOSTIC EVALUATION OF
(CCh), the non selective antagonist atropine and the M3 MICROPAPILLARY TRANSITIONAL
selective antagonists darifenacin and J104129, and different CELL CARCINOMA AFTER CYSTECTOMY?
selective antagonists of ERK and PI3-Kinase pathways. Total
Nicola Arrighi1, Francesca Benedusi1, Luca Cristinelli1,
RNA was extracted and retrotranscribed, to evaluate the gene
Regina Tardanico2, Alessandro Musesti3, Marco Finamanti1,
expression of the chosen cholinergic markers (muscarinic
Sergio Cosciani Cunico1, Claudio Simeone1
receptor, VAChT, ChAT, CarAT) by quantitative RT-PCR (Q-
RT-PCR). Immunofluorence was conducted to evaluate the 1UniversitàDegli Studi Di Brescia Cattedra Di Urologia;
protein expression of the cholinergic enzymes. Adenylyl 2IIServizio Di Anatomia Patologica Spedali Civili Di
cyclase activity and IP3 measurement were carried out using Brescia;
commercially available radioimmunoassay kits (Perkin Elmer, 3Cattedra Di Matematica Università Cattolica Del Sacro

Milano, Italy) on UROtsa cell extracts. Cell proliferation was Cuore- Brescia, Italy
determined by the evaluation of [3H]- thymidine incorporation
and by the MTT adsorbance assay. The statistical analysis was Introduction: Micropapillary transitional bladder cancer is one
carried out using the one-way ANOVA, with a post-hoc test of the most aggressive subtypes of urothelial carcinoma.
for multiple comparisons, considering p<0.05 as threshold for Almost rare, it is considered not responsive to conservative
significant difference. Results: Q-RT-PCR studies treatment (e.g. BCG). Our aim was to evaluate if evidence of
demonstrated the presence of an ACh synthesis/storage pT1 disease after radical cystectomy was associated to a better
mechanism in UROtsa cells. Indeed, we detected mRNA for prognosis in relation to pT2 disease. Patients and Methods:
ChAT, CarAT and muscarinic receptor subtypes M1-M5 From 1998, we stored perspectively data about all diagnoses
(range of expression that is: M3>M2>M5>M1>M4), while no of micropapillary bladder carcinoma (n=78). In 23 cases,
PCR product was obtained for VAChT. Immunofluorescence radical cystectomy has been performed as first treatment. At
confirmed the presence of ChAT and CarAT at the protein definitive analysis pT1 (n=7) or pT2 (n=16) were detected, by
level. By radioimmunoassay, we demonstrated that muscarinic confirmation of micropapillary disease features. In every case,
receptor mRNAs were translated into their proteins, an uretero-ileo-cuteaneostomy was performed (Wallace II
functionally linked to their known second messenger type). Mean follow-up period was 36 months (3-103).
pathways. Effects of muscarinic receptor stimulation on Analysis of OS in two groups was carried out by t-test and
UROtsa cell proliferation were explored and results Mann-Whytney test. Results: Mean OS in pT1 group was
demonstrated that CCh (1-100 μM) concentration-dependently 32.86 m (15-71), in pT2 38.2 (3-103). In fact in both tests, p-
enhanced cell proliferation. This phenomenon was value was quite high (t-test: 0.35, U-test: 0.44), showing a
antagonized by the non selective muscarinic receptor quite significant similarity in prognosis between two groups.
antagonist atropine and the M3-selective antagonists Discussion: A quite high p-value in two tests could suggest
darifenacin and J104129. The increase in cell proliferation that also increment of number of patients would not bring a
evoked by 50 μM CCh was blocked by either 1 μM PD98059 quite significant change in results. Absence of invasion of
or 1 μM U0126, indicating that the stimulation of proliferation muscular layer in fact is not related to better prognosis, and in
involved the ERK pathway. Similar experiments with these patients a quite strict follow-up must be proposed. At
consistent results for all three PI3-kinase inhibitors least, follow-up must be strict as in muscle-invasive disease.
demonstrated involvement of that pathway as well. Discussion On the other side, in literature (level 1a, EAU Guidelines)
and Conclusion: UROtsa cells expressed the machinery for debate about use of adjuvant chemotherapy is still going on. In
ACh synthesis and functionally active muscarinic receptors. fact, we suggest that, if performed, adjuvant chemotherapy
The cholinergic receptor agonist CCh stimulated UROtsa cell could be proposed also in pT1 patients. So, it could be
proliferation via a pathway apparently involving M3-receptors, confirmed that radical cystectomy is mandatory not only
ERK and PI-3 kinase. Our results on the stimulation of because BCG is not effective, but also because NMI disease
urothelial cell proliferation induced by cholinergic agonists seems so aggressive as pT2 disease.

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

54 Paolo Pedrazzoli1, Sinoma Secondino1, Ilaria Turin2,

IS SURGICAL APPROACH TO “ATYPICAL” Chiara Paglino1, Camillo Porta1, Daniela Montagna2
METASTASIS FROM RENAL CELL
CARCINOMA EFFECTIVE? 1OncologiaFondazione IRCCS Policlinico San Matteo,
2Laboratorio
di Immunologia dei Trapianti Fondazione
Nicola Arrighi, Alessandro Antonelli, Serena Corti,
IRCCS Policlinico San Matteo, Italy
Stefano Legramanti, Tiziano Zanotelli, Alberto Cozzoli,
Sergio Cosciani Cunico, Claudio Simeone
Background: Although renal cell carcinoma (RCC) is
Università degli Studi di Brescia Cattedra di Urologia, Brescia, considered to be an immunogenic tumor, T cell-based
Italy immunotherapy (IT) in metastatic RCC have so far shown
limited success. We recently demonstrated the feasibility of
Introduction: Clinical characteristics and oncologic results are expanding large amounts of autologous anti-tumor cytotoxic
objects of this study in patients who underwent surgical removal T-cells (CTLs), derived from peripheral blood of patients
of metastasis from renal cell carcinoma (RCC) in atypical sites affected by different types of solid tumor. Patients and
(atypical metastasis – AM – i.e. metastasis in sites other than Methods: CTLs were generated stimulating CD8-enriched
chest, liver, bone, adrenal, brain, kidney, lymph nodes), lymphocytes with Dendritic Cells pulsed with fresh autologous
compared to patients submitted to metastasectomy due to a lung apoptotic tumor cells, in the presence of IL-12 and IL-7.
metastasis (LM). Patients and Methods: We collected data from Specific anti-tumor CTLs were then rapidly expanded in an
an institutional database of about 1800 patients surgically antigen-independent way. The major advantage of this
treated for a RCC. We retrospectively identified 37 cases approach is that it involves the use of whole tumor cells as the
undergone metastasectomy for AM, and 57 patients operated for source of tumor antigens, circumventing the requirements for
LM. We compared clinico-pathological features of the primary the definition of specific tumor antigens or the presence of a
RCC and metastasis and Cancer Specific Survival (CSS) from defined HLA specificities. In a pilot study, we have treated
metastasectomy of patients with AM and LM. We performed with specific anti-tumor CTLs several patients with different
univariate and multivariable analysis applying a Cox regression tumors, including one patient affected by RCC. Results: Here
model to evaluate CSS. Results: The patients with AM and LM we briefly report on the case of a 62 years old male with clear-
were followed for an average of 40.8 and 50.7 months from cell RCC (diagnosed in 1999 and initially treated with
metastasectomy, respectively (p=0.372). No significant nephrectomy) who, in 2005, had large tumor masses in the
differences between patients with AM and LM were found in residual kidney and soft tissues as well as lung metastases, in
the characteristics of the primary tumour. In the cases with AM progression after the failure of 2 lines of conventional therapy
and LM the diagnosis was simultaneous with that of the primary (namely, IFN-alfa plus Vinblastine and IL-2). Patient received
tumour in 32.4% and 24.6%, (p=0.40) respectively, and, when lymphoablation with fludarabine and cyclophosphamide
metachronous, occurred at an average distance of 53.4 and 44.3 followed by CTL infusions on day +14 and +28 and every 2 to
months (p=0.370). More frequently, in the cases with AM other 4 months thereafter (median CTL n. 1.6×108, range 0.83-4).
metastases had been diagnosed in the previous medical history Disease remained stable according to RECIST criteria for 3
(35.2% vs. 8.8%, p=0.001) or simultaneously (48.6% vs. 8.8%, years, then progressive renal dysfunction, mainly due to an
p=0.001). Discussion: CSS from metastasectomy was affected increase in the kidney lesions, occurred, while all the other
by the synchronicity in diagnosis between metastasis and metastatic sites remained stable. Patient underwent a second
primary tumour, and by the simultaneous presence of other nephrectomy and continued CTL therapy during dialytic
metastases, while the type of metastasis (AM vs. LM) did not replacement therapy. Disease remained stable for additional 3
affect CSS. In fact, metastasectomy in atypical metastasis is years, then progressed at many sites, including brain.
effective at least as in lung metastasis. AMs are an exceptional Treatment with Sorafenib was attempted, with no benefit and
presentation of metastatic RCC, but the role of surgery is similar patient died of progressive disease in a few months. All the
to that of pulmonary metastases. In these cases, metastasectomy CTL infusions were well tolerated, and there was no evidence
is accepted as a possible care, and in AM the CSS after of clinically significant autoimmunity. The adverse effects
metastasectomy is alike. were minor and did not require medical intervention.
Immunological monitoring demonstrated that CTL infusions
can induce an increase in specific anti-tumor response
55 measured in the peripheral blood of the treated patient. Since
RATIONAL BASIS AND FIRST CLINICAL that first case, two additional patients have been treated
EXPERIENCE WITH AUTOLOGOUS recently, within an ongoing compassionate use program in
SPECIFIC T-CELL THERAPY IN RCC, confirming the feasibility and safety of the procedure.
ADVANCED RENAL CELL CANCER Enrollment is presently continuing at our site. Conclusion:

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

Treatment with specific autologous antitumor CTLs is safe Inclusion criteria were no evidence of active infection or
and induced immunological response and clinical benefit in inflammatory disease, no neo-adjuvant androgen therapy, PSA
one patient with RCC. The ongoing study will define, in a <20 ng/ml, clinical stage <IIc. Patients were classified by
larger series. whether this form of immunotherapy has a role clinical stage, pathologic Gleason sum, and significant GSU.
in advanced heavily pre-treated RCC patients. Significant GSU is defined as a Gleason sum increase between
biopsy and RP either from <6 to >7 or from 7 to [Link]
1 Montagna D et al: Feasibility and safety of adoptive stage was assigned by the attending urologist according to the
immunotherapy with ex vivo-generated autologous, cytotoxic 2002 TNM system. Between 14 and 16 needle biopsy cores
T lymphocytes in patients with solid tumor. Cytotherapy 14: were obtained under transrectal-ultrasound (TRUS) guidance:
80-90, 2012. 40 (74%) had 14 cores taken and 15 (27%) had 16 cores
2 Porta C et al: Immunological effects of multikinase taken. Primary and secondary Gleason score were assigned by
inhibitors for kidney cancer: a clue for integration with the same pathology Results: We found that IGFBP-3 median
cellular therapies? J Cancer 2: 333-338, 2011. levels were significantly lower in patients who showed
3 Pedrazzoli P et al: Is adoptive T-cell therapy for solid tumors Gleason upgrading from biopsy to RP (p=0.024). We also
coming of age? Bone Marrow Transplant. 2011 Aug 1. doi: found an association between biopsy T-stage and Gleason
10.1038/bmt.2011.155. [Epub ahead of print]. Upgrade (p=0.011). Using multivariate logistic regression
model, we demonstrated that the association of IGFBP-3
serum levels together with biopsy T-stage and biopsy Gleason
56 score was useful to calculate a prognostic risk score. ROC
ASSOCIATION OF PREOPERATIVE curve analysis of risk score showed a good ability to predict
PLASMA LEVELS OF INSULIN-LIKE GSU (AUC=0.81; 95% CI 0.69-0.93). Discussion and
GROWTH FACTOR-BINDING PROTEIN-3 Conclusion: Our results suggest that preoperative IGFBP-3
(IGFBP-3) WITH GLEASON SUM UPGRADING circulating levels determination may be useful to predict
Gleason score upgrading alone and/or in combination with
Matteo Ferro1, Florestano Montanino1,
biopsy T-stage and biopsy Gleason score.
Antonio Di Girolamo1, Daniela Terracciano2,
Claudia Mazzarella2, Ada Marino2, Alessandra Sorrentino2,
1 Mikolajczyk SD, Song Y, Wong JR, Matson RS and
Marco De Sio3, Sisto Perdonà4, Giovanni Castelluzzo1,
Rittenhouse HG: Are multiple markers the future of prostate
Pierluigi Bove5, Mariano Marsicano1, Vincenzo Altieri6
cancer diagnostics? Clin Biochem 37(7): 519-528, 2004.
1Urologia, Università degli Studi Federico II, Napoli; 2 Fradet Y: Biomarkers in prostate cancer diagnosis and
2Patologia Clinica Università Federico II, Napoli; prognosis: Beyond prostate-specific antigen. Curr Opin Urol
3Urologia, Seconda Università degli Studi di Napoli; 19(3): 243-246, 2009.
4Urologia, Istituto Nazionale Tumori IRCCS, “Fondazione 3 Baxter RC: Insulin-like growth factor (IGF)-binding
G. Pascale”; proteins: Interactions with IGFs and intrinsic bioactivities.
5Urologia, Università Tor Vergata, Roma; Am J Physiol Endocrinol Metab 278(6): E967-E976, 2000.
6Urologia, Università degli Studi di Salerno, Italy

Background: About 43% of men with low Gleason grade 57

prostate cancer (PCa) at biopsy will be finally diagnosed with PROSTATE CANCER BEYOND SURGERY.
high-grade PCa at radical prostatectomy (RP). Gleason sum at PSYCHOSOCIAL PROBLEMS AND UNMET NEEDS
RP is a good indicator of biochemical recurrence and poor
Anna Costantini1, Serena Brunetti1, Chiara Navarra1,
clinical outcome. Therefore, there is a need to improve clinical
Angelo Picardi2, Maria Chiara Greco3,
evaluation of PCa aggressiveness in order to choose an
Francesco Esperto3, Stefano Petta3
appropriate treatment. To this aim an easy-available tool is
represented by circulating biomarkers. Among these, the best 1UOD Psiconcologia, Azienda Ospedaliera Sant’Andrea,
candidates are some molecules involved in PCa pathogenesis Roma,
such as IGFBP-2 and IGFBP-3, IL-6, and its soluble receptor 2Statistica, Istituto Nazionale di Statistica,

(SIL-6R). Patients and Methods: In this study, we evaluated 3UOC Urologia Azienda Ospedaliera, Sant’Andrea, Roma,

the ability of preoperative IGFBP-2, IGFBP-3, IL-6, and SIL- Italy

6R serum levels to predict Gleason score upgrade in PCa
patients undergoing radical prostatectomy. During a 1-year Background: Prostate cancer is the most common neoplasm in
period, a total of 52 subjects with PCa, age ranging from 51 to male population after the fifth decade of life. Despite great
75 (median=64 years), were enrolled at our institution. advances in medical and surgical treatments, a prostate cancer

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

diagnosis still involves a profound alteration of the adequacy of information and informed consent in the short to
psychological status of the patient, considering also the medium-term, to psychological needs and the psychosocial
important role of prostate in personal and social life. The consequences of diagnosis and treatment in follow-up also in
tendency to underestimate emotional distress in cancer patients patients with a better prognosis. This possibility is certainly
has been repeatedly emphasized. This trend deprives patients achievable through a virtuous and effective integration
of the opportunity to undergo psycho educational and between urology and psycho oncology units.
psychotherapeutic interventions of proven effectiveness. Aim
of this study is therefore the assessment of the patient’s unmet 1 Grassi L, Biondi M and Costantini A: Manuale pratico di
needs and distress, especially with regard to the specific Psiconcologia, Il Pensiero Scientifico editore, Roma 2003.
complications of radical prostatectomy such as urinary 2 Costantini A: Considerazioni etiche e psicosociali in
incontinence and erectile dysfunction. Patients and Methods: oncologia. In Lopez M. Oncologia medica pratica, Società
From 2008 to 2010, 120 patients (mean age 65.97, SD 5.9) Editrice Universo, 2009.
were enrolled in the study for a psycho oncological evaluation.
All patients underwent retropubic radical prostatectomy for
organ-confined prostatic cancer about one year before and 58
were free of malignancy at the moment of the enrollment. SYSTEMATIC-EVALUATION OF THREE
After the surgical treatment at the third consecutive rise in SOFTWARE-SOLUTIONS FOR AUTOMATIC
PSA, 24 patients underwent radiotherapy, 19 hormonal therapy SEGMENTATION FOR REDELINEATION OF
and 1 chemotherapy. All participants administered a semi- TARGET AND OAR IN PROSTATE-CANCER
structured interview, properly designed for the study, on unmet
Mariangela La Macchia, Francesco Fellin
needs and a battery of self-assessment instruments such as the
FACT-P and the Hospital Anxiety and Depression scale Protonterapia APSS - ATreP, Trento, Italy
respectively to assess the health-related quality of life and to
detect states of depression and anxiety. Results: The interview Aim: To validate, in the context of adaptive radiotherapy, three
showed that although 77% of patients became affected by commercial software solutions for atlas-based segmentation
impotence and 58% by urinary incontinence they were overall through a comparison with manual delineation of target and
satisfied with the information received at the moment of the OAR in five patients affected by prostate tumor. Patients and
diagnosis and treatment. 87% reported having had an active Methods: Five previously treated high-risk prostate cancer
role in the treatment choice, 94% believed to have been given patients (PSA>20 ng/mL, Gleason score 8-10 or c/pT3a/b)
adequate information to choose between different treatment were enrolled in the study. The clinical target volume (CTV)
options, 85% thought to have been adequately prepared for the encompassed the prostate and seminal vesicles (definitive
adverse affects of the treatment, 90% estimated that doctors irradiation, three patients) or prostatic bed (post-operative
have given attention to their needs for information as to the irradiation, two patients) and pelvic lymph-nodes. The defined
recent positive changes in the doctor-patient communication organs at risk (OARs) were: rectum, bladder, femoral heads
field. In a limited percentage of cases, however, 23% of and bowel. In addition to the treatment planning CT (pCT)
patients highlighted unresolved psychosocial problems such images, one CT image set was acquired for each patient during
as the reduction of self-confidence as result of the diagnosis the RT course. An experienced physician manually outlined on
and treatment, 16% concerns about the diagnosis, 10% a the pCT and replanning CT (rCT) all the volumes of interest
pessimistic vision of the future, 10% a lack of acceptance of (VOI). These VOIs represented our atlas for the automatic
the disease, 25% heavy negative emotional effects related to contouring (AC) of the replanning CT. We used three software
impotence and incontinence and 17% sexual problems that solutions (VelocityAI 2.6.2 (V), MIM 5.1.1 (M) by MIMVista
might affect the relationship with family members. The corp and ABAS 2.0 (A) by CMS-Elekta to generate the AC.
presence of unmet needs and negative psychosocial All the VOIs obtained with AC were successively corrected
consequences of the intervention was associated with worse manually. Several times these were calculated and recorded: 1)
general and specific quality of life and higher levels of anxiety for ex novo ROIs definition on rCT; 2) for generation of AC by
and depression. Discussion and Conclusion: In this study a the three software solutions; 3) for manual correction of AC.
detailed investigation of the emotional state and unmet needs To compare the quality of the volumes obtained automatically
through a properly designed interview that documented in a by the software solutions and manually corrected with those
significant proportion of patients the presence of difficulties drawn from scratch on rCT, we used the following indices:
and problems whose clinical significance is suggested by its overlap coefficient (DCS), sensitivity, inclusiveness index,
association with worse quality of life and greater severity of difference in volume, and differences of displacements on three
psychopathological symptoms. The results suggest that it is axes (x, y, z) from the isocenter. Results: The time savings for
very important to foster a good fit to pay attention both to the all three softwares, compared to the manual contouring from

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

scratch, are statistically significant. On average, the shortest hundred fiftyfive (78%) were men. Out of 327 patients only
time it takes for the generation of automatic contours and for 72 (22%) underwent a physical examination comprehensive of
manual correction is always obtained with MIM. In regards to the external genitalia in the previous five years. The remaining
the overlap (quality) of volumes, the organs that are closer to 250 (76.4%) patients were not examined and, more relevant,
the volumes generated manually by the physician are the they did not ask for. Forty-nine (63.6%) out of the 77 patients
femoral heads, in all software solutions. Those most susceptible were examined on their specific request. Only 172 (52.6%)
to change are represented by the bowel and rectum. patients underwent laboratory and/or imaging assessment
Furthermore, a greater uncertainty in the automatic definition before urological councelling. Gross haematuria was the main
of the contours has been observed in both the cranial and urological symptom in 91 (27.8%) of cases. The general
caudal areas. Conclusion: From a clinical point of view, the practitioner was not adviced of patients’ symptom in 13% of
automated contouring workflow was shown to be significantly cases and, when informed, a urological assessment was
shorter than the manual contouring process from scratch, even required in only 47%. Discussion and Conclusion: Our
though manual correction of the VOIs is always needed. For a preliminary survey point out a limited attention to the
prostate patient this is about 40 minutes less. For all patients, genitourinary diseases both from the general practitioner and
the time saved by using the software products was comparable the patient. Noteworthy, in case of gross haematuria 20% of
and, compared to manual contouring, was statistically the patients did not inform the family doctor and a urological
significant. assessment was indicated in only 50% of cases.

59 60
THE GENITOURINARY DISEASES HEALTH-CARE PLASMATIC SIL 6R/IL-6 RATIO AS A
AMONG PATIENTS AND GENERAL PRACTITIONER POTENTIAL PREDICTOR OF HIGH GLEASON
SUM AT RADICAL PROSTATECTOMY
Vincenzo Serretta1, Francesco Sommatino1, Salvatore
Romeo1, Vincenza Alonge1, Giovanni Caruana1, Nino Matteo Ferro1, Florestano Montanino1, Mariano Marsicano1,
Dispensa1, Rosalinda Allegro2, Carlo Pavone1 Vittorino Montanaro1, Daniela Terracciano2, Ada Marino2,
1Urologia, Ester Illiano1, Domenico Prezioso1, Marco De Sio1,
A.O.U.P. Policlinico Paolo Giaccone,
2Statistica Renato De Domenico3, Domenico Sorrentino3,
GSTU Foundation, Italy
Giuseppe Quarto3, Sisto Perdonà3,
Vincenzo Serretta4, Vincenzo Altieri5
Introduction: A general awareness of the most common
genitourinary diseases is often [Link] aim of the present 1Urologia, Università degli Studi Federico II, Napoli;
study was to investigate the attention of the general 2Patologia, Clinica Università Federico II, Napoli;
practitioner and of the patient to the genitourinary diseases. 3Urologia, Istituto Nazionale Tumori IRCCS “Fondazione G.

An incomplete medical history and/or an inadequate physical Pascale”;

examination might be responsible of late diagnosis and 4Urologia, Università degli Studi di Palermo;

improper management. Patients and Methods: A self 5Urologia, Università degli Studi di Salerno, Italy

administered questionnaire was obtained by our outpatients

before the urological visit. As a preliminary step we Background: Approximately 40% of males with low Gleason
administered a very simple questionnaire consisting of four grade clinically localized prostate cancer (PCa) at biopsy were
multiple choice questions: 1) Did your general practitioner finally diagnosed with high Gleason grade PCa at radical
examine your external genitalia in the last five years? Did you prostatectomy (RP). Therefore, a more reliable assessment of
ask for this examination? 2) Did your general practitioner the Gleason grade prior to RP is required. Readily available
prescribe any clinical investigations? 3) Have you ever seen modalities such as circulating biomarkers may be useful for
blood in your urine? Did you advise your doctor? 4) How long this purpose. The aim of this study was to evaluate the ability
time did elapse between the first symptom and our of preoperative interleukin 6 (IL-6) and its soluble receptor
councelling? The study should be closed if less than 5 patients (sIL-6R), as well as urokinase-type plasminogen activator (u-
among the first 20 showed an improper attention to PA), its receptor (u-PAR) and the inhibitor (PAI-1) to predict
genitourinary pathology, otherwise, 200 consecutive patients Gleason score upgrading. Patients and Methods: A total of 51
at least should be entered. A further structured interview was PCa patients with biopsy Gleason score ≤7 were studied.
planned in the case of doubtful results. Results: From Preoperative serum samples were collected prior to digital
December 2011 to February 2012, 327 questionnaires were rectal examination (DRE) and TRUS. Blood was collected into
obtained from 358 patients with a compliance of 91.3%. The non-heparinized tubes and serum was separated within 1 h of
median age of the patients was 61 years (range: 15-91). Two blood collection. The serum was stored at –80˚C and then

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

thawed just prior to testing. Serum levels of PSA, free-PSA and patients with a biopsy GS ≤7. Moreover, this ability appears to
IL-6 were measured using the Immulite 2000 automated assay be enhanced by calculating the sIL-6R/IL-6 ratio. These
(DPC, Los Angeles, CA, USA). The concentrations of sIL-6R findings may provide an additional ‘staging tool’ for PCa
(R&D Systems, Minneapolis, MN, USA), uPA, uPAR and PAI- patients, which may be of great significance in guiding
1 (Assaypro, Winfield, MO, USA) in serum were determined clinicians’ treatment choices, according to current guidelines.
according to the manufacturer’s instructions using the ELISA
test. Every sample was run in duplicate and the mean was used. 1 Shariat SF, Andrews B, Kattan MW, Kim J, Wheeler TM
The differences between the two measurements were minimal. and Slawin KM: Plasma levels of interleukin-6 and its
Results: GS upgrading was defined as a Gleason sum increase soluble receptor are associated with prostate cancer
between biopsy and RP from ≤7 to >7, since this is important progression and metastasis. Urology 58: 1008-1015, 2001.
for the therapeutic strategy. On this basis, an upgrade was noted 2 Spiotto MT and Chung TD: STAT3 mediates IL-6-induced
in 5 (10%) samples. Median sIL-6R values were found to be neuroendocrine differentiation in prostate cancer cells.
significantly higher in patients with GS upgrading (difference Prostate 42: 186-195, 2000.
in medians, 28.40 ng/ml; 95% CI, 5.60-49.44; p=0.024). The 3 Deeble PD, Murphy DJ, Parsons SJ and Cox ME:
association between sIL-6R and GS upgrading became more Interleukin-6-and cyclic AMP-mediated signaling potentiates
significant by using the sIL-6R/IL-6 ratio (difference in neuroendocrine differentiation of LNCaP prostate tumor
medians, 7.77; 95% CI, 1.72-11.28; p=0.011). Sensitivity and cells. Mol Cell Biol 21: 84718482, 2001.
specificity of sIL-6R and the sIL-6R/IL-6 ratio were explored
by ROC curve analysis (Figure 1).
61
CHANGES IN HEALTH-RELATED
QUALITY OF LIFE OVER THE FIRST
YEAR IN ACTIVE SURVEILLANCE
Maria Francesca Alvisi1, Lara Bellardita1,
Tiziana Rancati1, Barbara Avuzzi1, Davide Biasoni2,
Tiziana Magnani1, Cristina Marenghi1, Silvia Stagni2,
Roberto Salvioni2, Riccardo Valdagni3
1Programma Prostata Fondazione, IRCCS Istituto
Nazionale dei Tumori, Milano;
2Divisione di Urologia Fondazione, IRCCS Istituto

Nazionale dei Tumori, Milano;

3Programma Prostata, Radioterapia Oncologica 1 Fondazione

IRCCS Istituto Nazionale dei Tumori, Milano, Italy

Background: The importance of the assessment of Health-

Related Quality of Life (HRQoL) has been fully acknowledged
when considering the implications of prostate cancer
treatments. In particular, the HRQOL of patients undergoing
Active Surveillance (AS) is currently under evaluation and data
Figure 1. ROC analysis comparing sIL-6R (--) and sIL-6R/IL-6 ratio are still sparse. The aim of this study was to evaluate changes
(–). in HRQoL during the first year in AS, also in comparison with
data reported in the literature. Patients and Methods: Between
The results indicated an extremely good ability to predict the November 2007 and January 2012, 132 patients were included
probability of biopsy Gleason sum upgrading of the two in PRIAS-QoL study and completed self-report questionnaires
parameters (sIL-6R: AUC=0.80; 95% CI, 0.63-0.97; p=0.026. at enrolment in AS protocol (Time 0). Evaluations after 10
sIL-6R/IL-6 ratio: AUC=0.84; 95% CI, 0.69-0.98; p=0.014). (Time 1) and 12 months (Time 2 - after the first re-biopsy)
The optimal cut-off point for sIL-6R was 76.5 ng/ml, providing were completed by 99 and 69 patients, respectively. Validated
a sensitivity of 80% and a specificity of 76%, whereas for the questionnaires assessing quality of life and psycho-social issues
sIL-6R/IL-6 ratio the optimal cut-off point was 13.5 with were administered, including Functional Assessment of Cancer
comparable sensitivity (80%), but higher specificity (83%). Therapy – Prostate Version (FACT-P), used to measure HRQoL
Discussion and Conclusion: sIL-6R may be a significant in terms of: physical wellbeing (PWB), social wellbeing
circulating biomarker employed to predict GS upgrading in (SWB), emotional wellbeing (EWB), functional wellbeing

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

(FWB), and wellbeing related to prostate cancer therapy 62

symptoms (PCS). Descriptive analyses were performed. EFFECT OF DECUBITUS ON PAIN
Correlation analyses were conducted to analyse the possible DURING TRANSRECTAL ULTRASOUND
association between FACT-P subscales and PSA (ng/ml). GUIDED PROSTATE BIOPSY
Repeated measure analyses of variance were performed to test
Marco Capece, Nicola Longo,
changes over time. Chi-square test was used to compare our
Ferdinando Fusco, Francesco Forchia,
data to FACT-P mean scores reported in another study (Lee, et
Francesco Bottone, Carmine Sciorio,
al.) including patients undergoing radical prostatectomy (RP),
Gaetano Gallo, Matteo Ferro,
external beam radiotherapy (EBRT), and interstitial
Ciro Imbimbo, Vincenzo Mirone
brachytherapy (IB). Comparisons were tested as follows: a) AS
to RP, EBRT, IB at T0; b) AS at T1 to RP, EBTR, IB at 12- Urologia, Università Degli Studi Federico II
month follow-up. Results: The mean age of study population
at Time 0 was 66.8 years (median 67, range 47-81). Descriptive Introduction: Transrectal ultrasound (TRUS)-guided prostate
data for FACT-P normalized scores are reported in Table I. biopsy can be perfomed in different positions like lithotomy
position, left or right lateral decubitus. Our primary objective
Table I. Descriptive analyses for FACT-P normalized scores (range was to assess whether patients’ pain perception differs as the
0-4). decubitus changes (lithotomy vs. left lateral decubitus). The
secondary objective is to assess whether the pain is caused by
Mean (SD)
the probe insertion, the core sampling or both. Patients and
HRQoL T0 T1 T2 Methods: We enrolled 96 men undergoing TRUSguided
prostate biopsy in our center, who accepted to sign an
PWB 3.9 (0.3) 3.8 (0.3) 3.9 (0.2) informed consent. Patients were randomized to perform the
SWB 2.9 (0.7) 2.7 (0.9) 2.9 (0.7) biopsy in lithotomy position (Group 1) or in left lateral
EWB 3.1 (0.6) 3.2 (0.6) 3.3 (0.5) decubitus (Group 2). All patients received a TRUS-guided
FWB 2.7 (0.7) 2.7 (0.6) 2.7 (0.5)
periprostatic nerve block (PPNB) before core sampling. At the
PCS 3.3 (0.4) 3.3 (0.6) 3.3 (0.7)
end of procedure we assessed pain felt at the time of probe
insertion and at the time of sampling by using a ten-point
No significant correlation was found between PSA and FACT- visual analog scale (0-9 VAS). Results: Patients of both groups
P. Scores that significantly changed over time were SWB and were comparable regarding age, total prostate-specific-antigen
EWB, which increased from T0 and T1 (respectively p=0.001, levels and volume prostate and number of cores. VAS scores at
p=0.0442) and from T0 to T2 (respectively p=0.014, the time of probe insertion were lower in Group 1 than in
p=0.0022). Repeated measure analyses of variance did not Group 2 (mean, 1.62 vs. 4.85; p<0.001), while VAS scores at
show significant changes between Time 1 and Time 2 for any the time of core sampling were equal in Group 1 and Group 2
of the subscales of the FACT-P. The increase in EWB showed (mean, 0.24 vs. 0.15; p=0.342). In both groups VAS scores at
in our data was reported also by Lee at one-year follow-up the time of insertion of the probe were significantly higher
from RP (p=0.0005). When we compared means of scores of than VAS scores at the time of core sampling (mean, 1.62 vs.
patients in AS with patients who underwent RP, IB, EBRT, we 0.24; p<0.001 in Group 1 and 4.85 vs. 0.15; p<0.001 in Group
found no significant differences both at entrance in AS/before 2). Discussion: In contrast to other studies which described
the treatment, and at follow-up evaluations. Conclusion: In left lateral decubitus as less painful, in our experience patients
accordance with relevant literature, our data, does not confirm who underwent a prostate biopsy in the lithotomy position
the concern about potential negative impact of AS on quality reported less pain than patients in left lateral decubitus.
of life: patients in AS did not show lower wellbeing compared Furthermore our study emphasizes that the probe insertion is
to patients undergoing radical therapies. Levels of HRQoL the most annoying moment of the prostate biopsy, suggesting
reported by patients undergoing AS are high, in particular as the importance of PPNB, regardless of decubitus.
far as physical and emotional wellbeing are concerned.
1 Kilciler M, Demir E, Bedir S, Erten K, Kilic C and Peker
Prostate Cancer Program, Multidisciplinary Clinic Team at AF: Pain scores and early complications of transrectal
Fondazione IRCCS, Istituto Nazionale dei Tumori, Milan; ultrasonography-guided prostate biopsy: effect of patient
Foundations I. Monzino and ProADAMO.
position. Urol Int 79: 361-363, 2007.
1 Esper P et al: Urology 50(6): 920-928, 1997. 2 Bruyère F, Faivre d’Arcier B, Haringanji DC, Boutin JM,
2 Lee WR et al: Int J Radiat Oncol Biol Phys 51(3): 614-623, Haillot O and Lanson Y: Effect of patient position on pain
2001. experienced during prostate biopsy. Urol Int 78: 351-355,
3 Singh J et al: Curr Urol Rep 11(3): 139-146, 2010. 2007.

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3 Heidenreich A, Bolla M, Joniau S, Mason MD, Matveev V, HRQoL”, while patients with scores higher than 25Th
Mottet N et al: EAU Guidelines. Arnhem: European percentile were identified as “normal-Q-HRQoL”. Chi-square
Association of Urology; 2011. Guidelines on prostate tests were performed to test the association between HRQoL
cancer. and adjustment to cancer. Results. The distribution of the Q-
ADJ (mean=–0.02, SD=1.96) was divided into 4 groups: from
the minimum value -6.41 to –1.96 (group 1=very low Q-ADJ),
63 from –1.96 to –0.02 (group 2=low Q-ADJ), from –0.02 to 1.96
ACTIVE SURVEILLANCE: IS HEALTH- (group 3=high Q-ADJ), from 1.96 to the maximum value 3.17
RELATED QUALITY OF LIFE ASSOCIATED (group 4=very high Q-ADJ). The percentage of patients with
WITH ADJUSTMENT TO CANCER? low-Q-HRQoL (Figure 1) were as follows: a) group 1=53.8%
(7 patients out of 13); b) group 2=27.6% (8 out of 28); c) group
Lara Bellardita1, Maria Francesca Alvisi1,
3=15.4% (6 out of 39);d) group 4=0% (no patients out of 13).
Tiziana Rancati1, Tiziana Magnani1, Cristina Marenghi1,
Chi-square test showed a statistically significant association of
Veronica Tresoldi1, Roberto Salvioni2,
worse adjustment to cancer with lower HRQoL (p=0.0001).
Nice Bedini3, Riccardo Valdagni4
1Programma Prostata Fondazione IRCCS Istituto Nazionale
Dei Tumori, Milano,
2Divisione Di Urologia Fondazione IRCCS Istituto

Nazionale Dei Tumori, Milano,

3Radioterapia Oncologica 1 Fondazione IRCCS Istituto

Nazionale Dei Tumori, Milano,

4Programma Prostata, Radioterapia Oncologica 1Fondazione

IRCCS Istituto Nazionale Dei Tumori, Milano, Italy

Background: Health-related quality of life (HRQoL) is

described as the extent to which one’s usual or expected
physical, emotional, and social well-being is affected by a
medical condition or its treatment. HRQoL has been associated Figure 1. Distribution of patients based on low/normal QoL and
adjustment of cancer.
with patients’ style of coping with cancer. The aim of this study
was to evaluate whether Active Surveillance (AS) patients’
HRQOL after 10 months is associated with styles of coping
with cancer as measured by mental adjustment to cancer, Conclusion: Patients undergoing AS generally report a
entailing appraisal of the implications of cancer, the ensuing satisfying HRQoL. Patients who show a more active and
reaction, and involuntary emotional reactions. This model flexible style of adjustment to cancer report higher satisfaction
identifies five strategies, namely: fighting spirit (FS), anxious with their level of wellbeing than those who find it difficult to
preoccupation (AP), fatalism (FAT), helpelessness/hoplessness adjust to their cancer. Those men may benefit from
(HH) and avoidance (AV). Patients and Methods: Between psychological counseling aimed at acquisition of more
November 2007 and January 2012, 145 patients entered the functional coping strategies.
PRIAS Quality of Life (QoL) study ongoing at the Prostate
Cancer Program of Fondazione IRCCS Istituto Nazionale dei Prostate Cancer Program Multidisciplinary Clinic Team at Fondazione
Tumori; 95 patients completed the assessment after 10 months IRCCS Istituto Nazionale dei Tumori, Milan; Foundations I. Monzino
and ProADAMO.
follow-up (Time 1), including: a) Functional Assessment of
Cancer Therapy – Prostate Version (FACT-P), used to assess
HRQoL, in terms of: physical wellbeing (PWB), social 1 Grassi L et al: Psychooncology 14(2): 115-124, 2005.
wellbeing (SWB), emotional wellbeing (EWB), functional 2 Barnett GC et al: Int J Radiat Oncol Biol Phys. 2011 May 21.
wellbeing (FWB), and wellbeing related to prostate cancer 3 Bonomi AE et al: Quality of Life Research 5(3): 309-320,
symptoms (PCS); b) Mini Mental Adjustment to Cancer scale 1996.
(Mini-MAC), evaluating FS, AP, HH, FAT and AV. A global
score (Q-score) (see Barnet et al. for definition) was calculated
by using the standardized scores of the distributions for both 64
Fact-P (Q-HRQoL) and Mini-MAC (Q-ADJ), both at Time 1. THE RISK OF LOW HEALTH-RELATED
Patients who had a Q-HRQoL less or equal to 25th percentile QUALITY OF LIFE IN PROSTATE CANCER
of the distribution of Q-HRQoL were identified as “low-Q- PATIENTS ON ACTIVE SURVEILLANCE

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

Lara Bellardita1, Maria Francesca Alvisi1, Tiziana Rancati1, several significant correlations between demographic features,
Tiziana Magnani1, Silvia Catania1, Cristina Marenghi1, personal experiences, motivation to enter PRIAS and adjustment
Nicola Nicolai2, Roberto Salvioni2, Sergio Villa3, to cancer and HRQoL. Amongst these, the ones that contributed
Riccardo Valdagni4 to the best model were: a) the presence of a partner which was
correlated with high SWB score (mean ranks 24.63 vs. 42.26,
1Programma Prostata, Fondazione IRCCS Istituto Nazionale p=0.0410); b) presence of comorbidities which was correlated
dei Tumori, Milano, with low PWB score (mean ranks 44.24 vs. 34.89, p=0.0381).
2Divisione di Urologia Fondazione IRCCS Istituto Nazionale The variables included in the best multivariate logistic model
dei Tumori, Milano, for HRQoL at Time 1 (total p=0.0002) were: Q-ADJ
3Radioterapia Oncologica, Fondazione IRCCS Istituto (continuous variable OR=0.54, p=0.0018), PSA (continuous
Nazionale dei Tumori, Milano, variable, OR=1.17, p=0.4311), presence of partner (OR=0.15,
4Programma Prostata, Radioterapia Oncologica, Fondazione p=0.0484), presence of co-morbidities (OR=0.21, p=0.0594).
IRCCS Istituto Nazionale dei Tumori, Milano, Italy The rock curve for the model is showed in Figure 1 (AUC=
0.753, 95%CI: 0.654-0.836).
Background: The potential anxiety and psychological distress
that could stem from observational management of prostate
cancer (PCa) are still debated. Different studies showed that
patients who choose Active surveillance (AS) report similar or
higher levels of Health-Related Quality of Life (HRQoL)
compared to patients who choose other therapeutic options
(such as prostatectomy, radiotherapy or brachyterapy).
Nonetheless, a minority of patients report some level of
psychological distress. The aim of this study is to evaluate the
individual factors that can be associated with the risk for AS
patients to experience low levels of HRQoL. Patients and
Methods: Between Nov 2007 and Jan 2012, 145 patients
entered the PRIAS QoL study, 132 completed questionnaires at
enrollment (T0) and 95 completed the assessment after 10
months follow-up (T1). The following questionnaires were
administered: a) A semi-structured interview including questions
related to demographic features, personal experiences and
motivation to enter PRIAS (Time 0); b) Functional Assessment
of Cancer Therapy – Prostate Version (FACT-P), measuring
HRQoL; subscales: physical wellbeing, social wellbeing, Figure 1. Rock curve for regression model (AUC= 0.753, 95%CI:
emotional wellbeing, functional wellbeing, and wellbeing 0.654-0.836).
related to prostate cancer symptoms. A Q-score (see Barnet et
al. for definition) was calculated (Q-HRQoL) for Time 1. The
25th percentile was used as cut-off for Q-HRQoL score, i.e. Conclusion: A negative style of adjustment to the idea of living
scores below 25th percentile=low Q-HRQoL, above 25th with (“untreated”) cancer and increases the risk of experiencing
percentile=normal Q-HRQoL; c) Mini Mental Adjustment to low HRQoL. The presence of comorbities did contribute to
Cancer scale (Mini-MAC), assessing adjustment to cancer, worse HRQoL in AS, probably because it was specifically
subscales Fighting Spirit, Helplessness/Hopelessness, Anxious assessed by referring to PCa. PSA level at entrance in AS seem
Preoccupation. A Q-score was calculated (Q-ADJ) for Time 1. to influence the risk (17%) of experiencing low HRQoL.
The 25th percentile was used as cut-off for Q-ADJ score, i.e. Patients may have protective factors such as the presence of a
scores below 25th percentile=low Q-ADJ, above 25th partner (which decreases the risk of having low HRQoL).
percentile=normal Q-ADJ. Prostate Specific Antigen (PSA) as Patients entering AS protocols could be helped in clarify how
measured at Time 0 was collected from medical records. they are dealing with their cancer and whether they have the
Kruskall-Wallis test was performed to evaluate the associations psychological and emotional support they may need in order to
between demographic features, personal experiences, motivation prevent the risk of impairment in their quality of life following
to enter PRIAS and adjustment to cancer on one side and cancer diagnosis and observational management of PCa.
HRQoL on the other side. A logistic regression was performed Prostate Cancer Program Multidisciplinary Clinic Team at Fondazione
to evaluate the variables that increased the risk of low HRQoL IRCCS Istituto Nazionale dei Tumori, Milan; Foundations I. Monzino
at 10 month-follow-up. Results: Kruskall-Wallis test showed and ProADAMO.

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

Bonomi AE et al: Quality of Life Research 5(3): 309-320, 66

1996. BENEFIT OF POST-DOCETAXEL TREATMENT IN
Grassi L et al: Psychooncology 14(2): 115-124, 2005. CASTRATION RESISTANT PROSTATE CANCER
Barnett GC et al: Int J Radiat Oncol Biol Phys May 21, 2011. PATIENTS WITH POOR PERFORMANCE STATUS
Amelia Altavilla, Roberto Iacovelli, Karen Truscelli,
Federica Morano, Emanuela Risi, Alessia Pochesci,
65
Valentina Lo Russo, Federica Urbano,
COMPARISON OF CANCER
Antonella Palazzo, Enrico Cortesi
DETECTION RATES BETWEEN
TRANSPERINEAL TEMPLATE Dipartimento di Scienze Radiologiche, Oncologiche ed
VERSUS MD ANDERSON PROTOCOL Anatomo-Patologiche Sapienza Università Di Roma, Italy
TRANSRECTAL PROSTATE BIOPSIES
Background: The landscape of treatment of castration resistant
Francesco Esperto1, Kasra Saeb-parsy2, Basil Moss2,
prostate cancer (CRPC) has recently changed. New molecules
Sarah Tang2, Mira Mikhai2, Ismail Omar2,
have demonstrated activity after docetaxel failure, but limited
Nikos Papoutsoglou2, Vincent Gnanapragasam2,
data are available about treatment of patients (pts) with a poor
Andrew Doble2, Christof Kastner2
performance status (PS). We performed a meta-analysis to
1Urologia Azienda Ospedaliera Sant’Andrea, determine the efficacy of second-line treatment for CRPC pts
2Dept. Of Urology Addenbrooke’s Hospital, Cambridge, with an ECOG PS=2. Patients and Methods: Randomized
U.K. controlled phase III trials (RCTs) in pts with CRPC who
progressed after docetaxel failure, were searched in MEDLINE
Introduction: The optimal method to investigate and PubMed databases. Abstracts from oncology meetings
persistently elevated PSA, High grade PIN or atypical were also taken into account. For each trial we evaluated the
small acinar proliferation (ASAP) after negative initial hazard ratio (HR) for overall survival (OS) and the relative
prostate biopsies remains unclear. Here we compared confidence interval (CI) limited to patients with PS=2.
cancer detection rates of two advocated prostate re-biopsy Statistical analyses were conducted to calculate the HR and
techniques: The Transrectal MD Anderson (MDA) protocol 95% CIs by using random-effects or fixed-effects models on
biopsy where both peripheral and transitional zones are the basis of the heterogeneity of included studies. Results: 5
biopsied and transperineal template biopsy (TPT). randomized controlled trials were found, but only 3 trials (1-
Materials and Methods: Patients in our institution who 3) (3149 pts) met the eligibility criteria for inclusion in the final
underwent MDA (n=365) or TPT (n=123) biopsy following analysis. In total, 291 patients (9.2%) had a PS 2. 181 were in
at least one negative standard biopsy were reviewed. the experimental arm: 15.5% received chemotherapy (CHT)
Cancer detection and where available, histological with cabazitaxel and 84.5% hormonal therapy (HT) with
correlation with pathology at radical prostatectomy were abiraterone acetate (45.3%) or MDV3100 (39.2%). 110 pts
recorded. Results: MDA biopsy had a cancer detection rate were in the control arm and received mitoxantrone (30%) or
of 29.3% (107/365). 61% of tumours in the MDA group placebo (70%). In the overall cohort the HR for OS was 0.758
were low risk, 20% intermediate risk and 19% high risk (95% CI 0.574-0.999, p=0.049), no significant heterogeneity
disease based on D’Amico classification. There was only a was observed (Q=0.510; p=0.774; I2=0%). The subgroup
25% grade concordance in patients who underwent radical analysis revealed that the HR for pts treated with CHT was
prostatectomy. Transperineal template biopsy had a cancer 0.81 (95% CI 0.477-1.373, p=0.434) and HR for pts treated
detection rate of 50.4% (62/123) which was significantly with HT was 0.739 (95% CI 0.534-1.023 p=0.068). Discussion
higher than the 29.3% detection rate in the MDA group and Conclusion: In this meta-analysis, we demonstrated a
(p<0.0001, Linear regression analysis). 16% of the significant improvement in OS also for CRPC patients with a
tumours in the TPT group were low risk disease, 45% PS=2 treated with second-line therapy after docetaxel failure
intermediate risk disease and 39% high-risk disease. There compared with control patients. Considering the small number
was grade concordance in 67% of the patient who of pts with PS=2 included in the trials, it is not possible to find
subsequently had radical prostatectomy. Discussion and out the best treatment option for this subgroup of pts.
Conclusion: TPT had higher clinically significant cancer
detection rate than MDA biopsy and more accurately 1 de Bono JS, Oudard S, Ozguroglu M et al: Prednisone plus
predicted final histology grade. We advocate TPT as first cabazitaxel or mitoxantrone for metastatic castration-
choice in the re-biopsy setting. MDA biopsy however resistant prostate cancer progressing after docetaxel
offers a reasonable alternative when TPT may not be treatment: a randomised open-label trial. Lancet 376: 1147-
appropriate. 1154, 2010.

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

2 de Bono JS, Logothetis CJ, Molina A et al: Abiraterone and clear cell carcinoma. Because of the extension of disease,
increased survival in metastatic prostate cancer. N Engl J surgery was excluded. In order to control bleeding and to treat
364: 1995-2005, 2011. patient with a less invasive approach TAE was proposed. TAE
3 Scher HI, Fizazi K, Saad F et al: Effect of MDV3100, an with embolization of branches of the celiac trunk, renal artery,
androgen receptor signaling inhibitor (ARSI), on overall superior mesenteric artery and collateral circulation was
survival in patients with prostate cancer postdocetaxel: performed. The procedure resulted in a rapid control of
Results from the phase III AFFIRM study. J Clin Oncol bleeding with improvement of clinical and laboratory
2012 (suppl 5; abstr LBA1). parameters. From December 2006 to April 2008 four TAE
sessions were carried out. No systemic therapy was
prescribed before the performance status. In July 2008 due to
67 improving of the clinical conditions sunitinib 50 mg/day (4/2
TRANS-ARTERIAL-EMBOLIZATION (TAE) w schedule) was prescribed. Treatment was well tolerated and
PLUS TARGET THERAPY (SUNITINIB) a tumor stabilization was evident after 6 months of therapy. A
IN RENAL CELL CARCINOMA (RCC) drug interruption of 4 months was spontaneously decided by
the patient and a later TC scan revealed a local disease
Sabrina Chiara Cecere1, Lucia Cannella2
progression with recurrence of pain. A further session of TAE
1Divisione di Oncologia Medica, Dipartimento was planned. In July 2010 imaging confirmed stable disease
di Oncologia Uroginecologica Istituto Nazionale of the primary tumor, but lung disease progression was
Tumori Irccs - Fondazione Pascale, observed. Sunitinib was restarted. Treatment was well
2Divisione di Oncologia Medica A.O.G. Rummo di tolerated without disease progression until september 2011.
Benevento, Italy Discussion: Angiogenic factors are shown to be
overexpressed in the hypoxic zone between the necrotic
Introduction: Surgery (radical or partial nephrectomy) central area induced by TAE implying a possible role for
remains the mainstay of treatment for RCC. Unfortunately, concomitant treatment. The rationale for the combined use
about one third of patients undergoing surgical resection for seems to be correlated to the pharmacological inhibition of
localized disease develops recurrence and is eligible for neoangiogenesis, detected after each session of embolization
systemic therapy. A proportion of patients is diagnosed at an (reduction of peripheric new vessels). Despite the limited
advanced stage. When surgery is not indicated, due to tumor experimental and clinical evidence for synergism and the
extension or poor performance status, there is still the skepticism for combining TAE with an antiangiogenic agent
indication for a locoregional therapy associated to systemic like sunitinib, mainly due to presumed increased incidence of
treatment in order to improve symptoms. Preliminary data adverse events, the combination of systemic therapy and TAE
with the association of locoregional therapy have been merit further investigation In our patient, surviving more than
published in renal cell carcinoma animal models: an increased 5 years after the diagnosis, the combined use of TAE and
efficacy has been showed with the combination of sorafenib sunitinib was well tolerated. Embolization allowed a good
and radiofrequency ablation. TAE has been proposed as a control of acute bleeding as well a local disease control for
nonsurgical ablative technique for the treatment of resectable 20 months without related complications. Sequential therapy
and non resectable tumors, being able to facilitate dissection with TAE and Sunitinib was feasible with no cumulative side-
reducing tissue planeoedema, bleeding and extent of tumor effects.
thrombus. Sunitinib, as antiangiogenetic therapy, is
considered standard first line treatment for renal cell 1 Bakke A, Gothlin JH, Haudaas SA et al: Augmentation of
carcinoma (RCC). Very few data are available on the natural killer cell activity after arterial embolization of renal
combination of systemic therapy with sunitinib and carcinomas. Cancer Res 42: 3880-3883, 1982.
locoregional treatment of the primary tumour by TAE. Case 2 Ginat DT, Saad WE and Turba UC: Transcatheter renal
Report: In september 2006, a 67 years old outpatient man, artery embolization for management of renal and adrenal
affected by type 2 diabetes mellitus and pharmacologically tumors. Tech Vasc Interv Radiol 13(2): 75-88, 2010.
handled hypertension came to our attention for right flank 3 Liu WG, Gu WZ, Zhou YB et al: The prognostic relevance
pain, hematuria, anemia (Hgb 5.0 g/dl) and severe asthenia. of preoperative transcatheter arterial chemoembolization
The CT scan with iodine contrast showed a massive neoplasm (TACE) and PCNA/VEGF expression in patients with
of the right kidney (maximum diameter 15 cm), with invasion Wilms’ tumour. Eur J Clin Invest 38(12): 931-918, 2008.
of the renal fascia, perirenal spaces, posterior abdominal wall 4 May M, Brookman-Amissah S, Pflanz S et al: Pre-operative
and psoas muscle. A thrombosis of renal and cava veins at the renal arterial embolisation does not provide survival benefit
edge of its infraepatic tract and infiltration of ipsilateral in patients with radical nephrectomy for renal cell
adrenal gland was evident too. The biopsy confirmed renal carcinoma. Br J Radiol 82(981): 724-731, 2009.

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

Author Year Therapy Control Phase Type of No of pts Incidence of CR (%)

of study study
AAs 95% CI Control 95% CI

Yuang et al. 2003 Bevacizumab 10mg Pbo 2 RCT 116 0 0

Bevacizumab 3mg Pbo 0 0
Escudier et al. 2007 Bevacizumab+IFN Pbo+IFN 3 RCT 649 1.3 0-2.7 2.1 0.3-3.9
Motzer et al. 2007 Sunitinib IFN 3 RCT 750 3.3 1.2-5.3 1.2 0-2.6
Rini et al. 2007 Bevacizumab+IFN IFN 3 RCT 731 3.4 1.3-5.5 1.3 0-2.7
Escudier et al. 2009 Sorafenib IFN 2 RCT 189 0 1.1 0-3.7
Sternberg et al. 2010 Pazopanib Pbo 3 RCT 435 0.3 0-1.2 0

Total 1.9 1.1-2.6 1.2 0.6-1.9

5 Maxwell NJ, Saleem Amer N and Rogers E: Renal artery patients with good or intermediate prognosis defined by
embolisation in the palliative treatment of renal carcinoma. MSKCC risk score. The proportion of patients with CR and
Br J Radiol 80(950): 96-102, 2007. the derived 95% confidence interval (CI) were calculated for
6 Facchini G et al: New treatment approaches in renal cell each study. We also calculated the relative risk (RR) and the
carcinoma. Anticancer Drugs 20(10): 893-900, 2009. CIs of events in patients assigned AAs compared to control in
7 Motzer RJ et al: Sunitinib versus interferon alfa in the same study. To calculate the 95% CIs, the variance of a
metastatic renal-cell carcinoma. NEJM 356: 115-124, 2007. log-transformed study-specific RR was derived using the delta
8 Schmidinger M et al: Optimizing the use of sunitinib in method. Statistical heterogeneity between trials included in the
metastatic renal cell carcinoma: an update from clinical meta-analysis was assessed using Cochrane’s Q statistic, and
practice. Cancer Invest 28: 856-864, 2010. inconsistency was quantified with I2 statistic (100% x [Q-
9 Thomas AA et al: Surgical resection of renal cell carcinoma df)/Q]) Results: Six RCTs (2986 pts) were found, four were
after targeted therapy. J Urol 182: 881-886, 2009. phase III and two were phase II RCTs (see table below). 2636
pts were evaluable for final analysis and randomized to receive
AAs (1429 pts) or control (1022 pts had IFN and 185 had
68 placebo). Patients were treated with bevacizumab (50%),
ANTIANGIOGENIC AGENTS ARE sunitinib (23%), pazopanib (20%) and sorafenib (7%). The
INEFFECTIVE TO INCREASE COMPLETE incidence of CR in pts treated with AAs was 1.9% (95%CI,
RESPONSE RATE IN MRCC. A META-ANALYSIS 1.1-2.6) compared to 1.2% (95%CI, 0.6-1.9) in the overall
control arms, among these the incidence of CR in the IFN was
Roberto Iacovelli, Amelia Altavilla, Antonio Passaro,
1.5% (95%CI, 0.7-2.3). The relative risk (RR) to have a CR
Giuseppe Maria Campennì, Daniele Alesini,
with AAs was 1.6 (95%CI, 0.8-3.0; Q=4.7, p=0.57; I2=0%)
Michela Palleschi, Daniela Modica,
but the data was not significant (p=0.15). If only phase III
Sara Giovannoni, Chiara Manai, Enrico Cortesi
RCTs were considered, the RR to have a CR was 1.7 (95%CI,
Dipartimento di Scienze Radiologiche, Oncologiche ed 0.9-3.4; Q=3.6, p=0.30; I2=17.2%) with a trend for
Anatomo-Patologiche Sapienza Università di Roma, Italy significance (p=0.08). No differences were found when AAs
were compared to IFNα alone (RR=1.6, p=0.14). Among
Background: Since their approval, antiangiogenic agents AAs, sunitinib reported the highest RR for CR (2.7; 95%CI,
(AAs) have increased overall survival (OS) in metastatic renal 0.9-8.3) with a trend for significance (p=0.088). Conclusion:
cell carcinoma (mRCC); moreover these agents have reported CR is a rare event in mRCC, and even if AAs reported greater
greater activity compared to interferon alpha (IFNα) with an activity in term of PFS and ORR, they did not increase the
increase of the progression free survival (PFS) and the overall curative rate of metastatic disease. Probably other biologic
response rate (ORR). Despite these advances, mRCC continue factors than angiogenesis may influence the CR in mRCC.
to be a fatal disease and the complete response (CR) to
therapy is a rare event. We meta-analyzed the incidence of CR
in pts treated with AAs and in controls in main randomized 69
control trials (RCT) for first line therapy in mRCC. Materials POLYMORPHISM IN THE PROSTATE
and Methods: Pub-Med and Medline search was performed to STEM CELL ANTIGEN GENE PSCA MODIFIES
find first line RCT with AAs vs. non-AAs for mRCC in SURVIVAL OF BLADDER CANCER PATIENTS

1890
 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

Paolo Destefanis1, Fulvio Ricceri2, Carlotta Sacerdote2, proliferation and migration; monoclonal antibodies targeted to
Andrea Bosio1, Mariateresa Carchedi1, Giovanni Casetta3, PSCA inhibit tumour growth and metastasis formation in
Paolo Gontero3, Giuseppina Cucchiarale4, animal models. PSCA is expressed at low levels in the
Giuseppe Matullo2, Silvia Polidoro2, transitional epithelium of normal bladder but it is
Simonetta Guarrera2, Rossana Critelli2, overexpressed in the majority of UBCs. A functional in vitro
Alessia Russo2, Dario Fontana5, Paolo Vineis2 study demonstrated that the variant allele significantly reduced
promoter activity. The biological mechanism of PSCA
1SC Urologia 2 AOU, San Giovanni Battista, Molinette; involvement in the modulation of survival for UBC is not
2Hugef Human Genetic Foundation, Torino; clear, however a recent study showed that the same SNP is
3SC Urologia 1 AOU San Giovanni Battista, Molinette, associated with gastric cancer survival (3). In conclusion, we
4SC Urologia Clinica Cellini; observed an association between PSCA polymorphism and
5SC Urologia 1-2 AOU, San Giovanni Battista, Molinette, survival in UBC. However more functional studies and
Italy replication of these in independent study populations are
needed to confirm our results.
Background: Urinary bladder cancer (UBC) ranks fifth in
Italian male cancer incidence with a worldwide age- 1 Ferlay J et al: Estimates of worldwide burden of cancer in
standardised rates per 100,000 of 20.1 (1). A recent genome- 2008: GLOBOCAN Wu X et al: Genetic variation in PSCA
wide association study on 969 bladder cancer cases and 957 gene confers susceptibility to urinary Wang M et al: Genetic
controls showed that a missense variant (rs2294008) in the variant in PSCA predicts survival of diffuse-type gastric 2008.
PSCA gene is consistently associated with UBC risk in US International Journal of Cancer 127(12): 2893-2917, 2010.
and European populations (2). Survival of UBC patients in bladder cancer. Nat Genet 41(9): 991-995, 2009. cancer in a
Western countries varies widely. Although the major Chinese population. Int J Cancer 129(5): 1207-1213, 2011.
prognostic determinants for UBC are stage and grade of the
tumour at diagnosis, there are wide unexplained differences in
survival time among patients with similar disease, general 70
condition and treatment. Until now, genetic single nucleotide DELIRIUM IN HOSPITALIZED
polymorphisms (SNPs) have been extensively studied in ELDERLY PATIENTS UNDERGOING
relation to the modulation of cancer risk. Few studies have UROLOGIC SURGERY. INCIDENCE AND
been conducted on the relationship between SNPs and UBC PREDICTIVE ROLE OF MULTIDIMENSIONAL
survival. The aim of the present study was to investigate the GERIATRIC EVALUATION (MGE) TO DEFINE
association between stem cell antigen gene PSCA variants and A HIGH-RISK POPULATION AND
survival from UBC. Materials and Methods: The study PREVENT COMPLICATIONS:
population included all the newly diagnosed, histologically RESULTS OF A PROSPECTIVE STUDY
confirmed cases of UBC registered at urology departments of
L. Bergamini1, M. Mannina1, G. De Luca2,
an academic hospital in Italy during the years 1994-2010. All
E. Bertellini3, M. Neri1, M. Brausi2
subjects were men, aged 40-75 years and living in the same
metropolitan area of the hospital. We genotyped cell antigen 1University of Modena and Reggio Emilia, Department of
gene PSCA (rs2294008) in 320 male UBC patients. For each Geriatrics;
SNP we estimated Hazard Ratios (adjHR) adjusted for 2AUSL Modena, Department of Urology;

potential confounders (age, stage, grading and type of therapy) 3Dept of Anesthesiology, Ausl Modena, Italy

and 95% Confidence Intervals (95%CI) for survival time.

Results: 126 patients died during the observation time, from Introduction and Objectives: Delirium (acute derangement
these 30 died for the consequences of their UBC. The median syndrome) is a common condition occurring in hospitalized
survival time was 5.83 years. Among the patients who died older pts with negative consequences, including higher post-
from UBC, variant alleles of PSCA conferred a statistically op complication rates and death, disability, permanent
significant worse survival (HR 1.68 95%CI 1.01-2.79, cognitive decline and institutionalization. It determines a
p=0.04). After adjustment for potential confounders the risk longer hospitalization and an increase of costs. It’s incidence
for variant allele carriers persisted with a borderline statistical ranges from 15 to 35% in postoperative phase, and from 70
significance (adjHR 1.76 95%CI 0.98-3.13, p=0.05). to 87% in intensive care (IC). Several studies have attempted
Discussion and conclusion PSCA was initially identified as a to set criteria delineating a high-risk profile to develop
prostate-specific cell-surface marker. It is overexpressed in delirium. The objective of this prospective study was to
prostate cancer, and the level of expression increases with evaluate the impact of a MGE in 3 settings of pts
tumour grade and stage. It may be involved in cell hospitalized for medical or surgical conditions and to

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

evaluate the incidence and the possible causes of delirium. Introduction/Background/Aim: Prostate cancer is the most
Methods: 274 elderly pts. admitted to 2 hospitals were widespread cancer amongst men in the Western world but its
evaluated in 3 different settings. 62 /274 pts (22.6%) from diagnosis and management are still a clinical challenge. We
different depts. received a MGE on request during their assessed the diagnostic performance of a combined
hospital stay (Group 1). 159/274 (58%) dismissed pts. and morphological and functional Magnetic Resonance Imaging
regularly followed as out-pts. had a MGE at home (Group (MRI) scoring system in urological-radiological work-up in
2). 53/274 pts (19.4%) admitted for an elective urological patients with a Prostate Specific Antigen (PSA) ≤10 ng/ml.
procedure had a pre-op and post-op MGE and were strictly Patients and Methods: We enrolled 186 consecutive patients
followed (Group 3).The mean age was 80.8, 80.3 and 78.1yrs with PSA value between 2.5-4 ng/ml, with abnormal findings
respectively. The MGE included 19 items that were recorded at Digital Rectal Examination (DRE), and patients with PSA
in all pts. (drug history, delirium rating scale .). In this last value between 4-10 ng/ml. This study was approved by the
group MGE was daily applied by nurses to define incidence local ethical committee. Each patient provided informed
and clinical characteristics of delirium. F-UP was planned at consent to undergo an urological-radiological work-up
1, 3 months and 1 year after discharge to evaluate global including serum free/total PSA ratio (f/t PSA) assay,
health and specifically functional and cognitive pts. status. morphological MRI (mMRI), MR Spectroscopy (MRS),
Results: In Group 1 (62 pts) 75.8% of pts had MGE positive Diffusion Weighted Imaging (DWI) and Trans Rectal
for delirium. Older age, high number of drugs used (digitalis Ultrasonography (TRUS) biopsy. MRI data sets were scored
and antibiotics) and depression were significantly correlated singularly, coupled and combined (cMRI score) to assess their
with delirium. In Group 2 (159 pts) 31.4% of subjects had diagnostic performance. Outcome Measurements and
delirium. Sex (females), >age, worse cognitive status and Statistical Analysis: Scores were correlated to negative
types of drugs used (digitalis, neuroleptics, antidepressant) biopsies and significant/insignificant Gleason score biopsies.
were correlated with delirium. In Group C (53 pts affected Receiver Operating Characteristic (ROC) curve and McNemar
by BPH and prostate, bladder and kidney cancer) 14.6% had tests were used to compare the diagnostic performance for all
a MGE test positive for delirium. Presence of co-morbidities, techniques and derived scores. Results: 136 patients were
ASA score III-IV, type of anesthesia (general vs. spinal) were included (average PSA value 6.8 ng/ml; f/t PSA 18.5%).
correlated with delirium. Conclusion: The incidence of Cancer was diagnosed in 18% of patients. Using a cut-off
delirium varies between the old population. MGE is an value=2, cMRI score showed the highest sensitivity (0.84) and
appropriate tool to detect it. Older age, low cognitive status, negative predictive value (0.93). cMRI score showed a
depression and N of drugs used are correlated with it. In significant correlation with Gleason score, and a statistically
urological pts candidate for surgery, high N of co- different median value between significant and insignificant
morbidities, ASA score III-IV and type of anesthesia Gleason score. Conclusion: cMRI score could identify patients
(general) predict the onset of delirium. Pharmacological with a PSA ≤10 ng/ml who will have a negative work-up,
research is ongoing to detect the variation of cholinergic thanks to its high negative predictive value, and patients at
agents that may also be responsible for delirium. high risk for significant Gleason score cancer because of its
correlation to Gleason score.

71 1 Umbehr M, Bachmann LM, Held U et al: Combined

WORK-UP IN PATIENTS WITHOUT A SPECIFIC magnetic resonance imaging and magnetic resonance
RISK OF PROSTATE CANCER (PSA ≤10 NG/ML): spectroscopy imaging in the diagnosis of prostate cancer: A
A MULTIPARAMETRIC MRI SCORING SYSTEM systematic review and metaanalysis. Eur Urol 55: 575-590,
2009.
Sisto Perdonà1, Giuseppe Quarto1, Renato De Domenico1,
2 Pondman KM, Fütterer JJ, ten Haken B et al: MR-guided
Domenico Sorrentino1, Matteo Ferro2, Vincenzo Altieri3,
biopsy of the prostate: An overview of techniques and a
Francesco Michele Ronza4, Venanzio Setola4,
systematic review. Eur Urol 54: 517-527, 2008.
Roberta Fusco4, Marco De Sio5, Riccardo Autorino5,
3 Sciarra A, Panebianco V, Salciccia S et al: Modern role of
Modestino Tronino2, Antonella Petrillo4
magnetic resonance and spectroscopy in the imaging of
1UOC-Urologia, Istituto Nazionale Tumori Fondazione “G. prostate cancer. Urol Oncol 29: 12-20, 2011.
Pascale”, Napoli;
2Urologia, Università Federico II, Napoli;
3Urologia, Università degli Studi di Salerno; 72
4Radiologia, Istituto Nazionale Tumori IRCCS “Fondazione HIGH RISK PROSTATE CANCER: MANAGEMENT
G. Pascale”, Napoli; ANALYSIS ACCORDING TO ONLINE-IMAGE-
5Urologia Seconda, Università degli Studi di Napoli, Italy GUIDED-INTENSITY-MODULATED-

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RADIOTHERAPY, OFFLINE-IMAGE-GUIDED- volume selection and delineation adapting correct RT

3DCONFORMAL-RT AND ALTERED VS. strategies to different biochemical, clinical and prognostic
CONVENTIONAL FRACTIONATION situations (3). We had acceptable interobserver variability in
targeting PNR but we need more data or automated
Marco Signor1, Marco Signor2, Alessandro Magli2,
segmentation methods to obtain a better definition of BTVs.
Agnese Prisco2, Sandro Fongione2,
Gioacchino De Giorgi3, Bruno Frea3, Rolando Berte’4
1 Lancet Oncol 12: 181-191, 2011.
1RadioterapiaOncologica Aou, S. Maria Della Misericordia; 2 Radiotherapy and Oncology 96: 347-350, 2010.
2Radiation Oncology Unit, University Hospital, Udine; 3 Tumori 97: 49-55, 2011.
3Urology Unit, University Hospital, Udine;
4Urology Unit, Civic Hospital, Gorizia, Italy

73
Background: In most patients, recurrence is suspected as a LAPAROSCOPIC PARTIAL NEPHRECTOMY:
result of an increase in PSA concentration. However, treatment WHAT DOES CHANGE AFTER MORE THAN
planning requires precise knowledge of the location and extent 250 PROCEDURES PERFORMED
of disease, which cannot be derived from biochemical data or BY A SINGLE SURGEON
nomograms alone. [18F]Choline PET/CT imaging is an
Francesco Porpiglia, Riccardo Bertolo, Ivano Morra,
established diagnostic tool in a single step re-staging patients
Fabrizio Mele, Daniele Amparore, Cristian Fiori
with biochemical failure after primary treatment for prostate
cancer (1). Actually, there are limited published data on the Divisione di Urologia AOU San Luigi Gonzaga, Italy
best method for targeting the Biological Target Volume (BTV)
(2) Aims: 1) to analyze our experience with [18F]Choline Introduction: The purpose of this study was to explore the
PET/CT imaging in radiotherapy planning of postoperative pathological outcomes of laparoscopic partial nephrectomy
recurrent prostate cancer; 2) to investigate the interobserver (LPN) for kidney tumour performed by a single surgeon in a
variability using visual method for targeting BTVs. Methods: single Institution after a decennial experience. Materials and
Since march 2010 to March 2011, seven consecutive patients Methods: We retrospectively reviewed our prospectively
(pts) with biochemical failure after radical retropubic maintained LPN database and we reviewed the 256
prostatectomy (RRP) +/– adjuvant radiotherapy (AR) were pathological specimens of kidney tumours treated by LPN at
studied to discriminate local or systemic recurrence and to our Institution by a single surgeon (F.P.) from January 2001
select second-line treatment. We acquired PET/CT imaging to to January 2012. A single uro-pathologist (E.B.) performed
detect morphologic and metabolic failure data and, pathological analyses according previously described criteria
subsequently, CT simulation-localization was performed. PET (1). The masses were divided into three Groups with a
to CT-planning was aligned through a mutual information-like chronologic criterion: cases from 1 to 85 were assigned to
method and the match was assessed acceptable. We adopted a Group A, from 86 to 170 were assigned to Group B whilst
different strategy regarding the choice of the volumes to the remainder 86 cases (from 171 to 256) were assigned to
irradiate and the doses to prescribe in accord to prostatectomy Group C. The three Groups were compared according to the
bed recurrence (PBR) vs. pelvic nodal recurrence (PNR) or following variables: intra-operative variables (warm ischemia
both. A team composed by four members, a radiation time, WIT, operative time and estimated blood losses, EBL),
oncologist, a nuclear medicine physician and two urologist lesions’ pathological size and weight, PADUA score (2),
defined BTVs using visual method on contouring software. staging according to TNM (3), minimum and maximum
Results: all the pts (mean age: 70.9 years, KPS 90) had a resection margin, mean of excised margin and rate of
postRRP recurrence, one postAR (66 Gy on the PB) and one positive surgical margins (PSMs). Groups were compared
androgen blockage (AB) refractory. Average time to relapse using Kruskall-Wallis Analysis of Variance (ANOVA) test.
was 66 months (range 35-107). [18F]Choline PET/CT Univariate linear regression model was used too in order to
imaging detected 4 PBR, 2 PNR and one synchronous PBR + verify the trend of studied variables along our case study (p-
PNR. We administered 74 Gy on PBR volume, 50.4 Gy on values<0.05 considered statistically significant). All
lymphatic pelvic volume in PNR and on pelvic volume in statistical analyses were performed using the “Statistica”
synchronous PBR + PNR. Five pts are in AB treatment. Inter- software program Ver. 6.0 (Tulsa, OK, USA). Results:
observer variability for visual delineation of BTVs was not Groups were similar in terms of pathological size
statistically significant in definition of site and size of PNR. (p=0.4675); PADUA score was significantly higher in Group
Instead, we noted some incoherence in size calculation of C (p<0.0001) maybe due to the more extended indication of
BTV related to PBR. Conclusion: In postRRP recurrence pts, LPN with the increasing experience of the surgeon.
[18F]Choline PET/CT imaging can address to a better target Nevertheless, WIT constantly decreased from Group A to

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

Group C (p<0.0001) due to the same reason; moreover, EBL 74

decreased along the case-study particularly in Group B CLAMPLESS LAPAROSCOPIC PARTIAL
(p<0.0001) and operative time slightly decreased along the NEPHRECTOMY: IS A HARMLESS NEPHRON-
learning curve. Duration of hospitalization was reduced SPARING SURGERY REALLY FEASIBLE?
along the case study too (p<0.0001). We registered an
Francesco Porpiglia, Riccardo Bertolo, Ivano Morra,
increase in the pathological weight of the lesions in Group
Fabrizio Mele, Marco Lucci Chiarissi, Cristian Fiori
B with respect to Groups A and C (p<0.0001). Out of the
256 lesions, 173 (67.6%) were defined malignant at the Divisione Di Urologia AOU San Luigi Gonzaga, Italy
histo-pathological analysis: the 64.7% (55/85), 67.0%
(57/85) and 70.9% (61/86), in Groups A, B and C, Background: An evolution of a known concept of laparoscopic
respectively. The distribution of malignant lesions stratified partial nephrectomy (LPN) has been taken into consideration
according to pathological TNM staging was: 111/173 in urological surgery: LPN performed by “zero-ischemia”-
(64.2%) pT1a, 49/173 (28.3%) pT1b, 5/173 (2.9%) pT2, technique (1), with the aim of completely eliminating surgical
8/173 (4.6%) pT3a-b; we did not find any statistically renal ischemia. In the present study, we retrospectively
significant difference in the distribution of TNM staging evaluated our experience with clampless-LPN (cl-LPN): the
inside the Groups. Minimum thickness of peri-tumoural aim was to evaluate the results of this technique and to
healthy tissue resected decreased continuously along the case compare results of cl-LPN with conventional LPN ones.
study (p<0.0001). Maximum resection margin was stable Patients and Methods: We reviewed our prospectively
and so the mean resected. There was no statistically maintained database: data of 117 patients who consecutively
significant difference in the percentage of PSM among the underwent LPN at our Institution from January 2009 to
Groups, with an overall rate of 2.3% (4/173); in particular December 2011 were extracted. Patients were divided into 2
no PSM were recorded in Group C. Our results were Groups based on operative technique: Group A: cl-LPN;
confirmed by univariate linear regression model that Group B: conventional LPN (with clamping of renal artery).
demonstrated that moving along our case study from the first Demographic and peri-operative data, complications, pre- and
cases to the latest, WIT, duration of hospitalization and post-operative serum creatinine (SCr) and estimated
minimum margin significantly decreased (p<0.0001, glomerular filtration rate (eGFR, calculated by MDRD
p=0.0474, p=0.0001, respectively) while lesions’ weight and formula (2)) were registered and compared by Student’s t- and
PADUA score significantly increased (p=0.0009, p<0.0001). Chi-square-tests (p-values<0.05 considered statistically
Conclusion: Our data suggest that, with the increase of significant). All statistical analyses were performed using the
surgeon experience along a learning curve of more than 250 “Statistica” software program Ver. 6.0 (Tulsa, OK, USA).
laparoscopic partial nephrectomies, even if the features of Results: Out of 117 patients who underwent LPN, 41
the lesions treated become more difficult, WIT is strongly underwent cl-LPN and constituted Group A. The remaining 76
reduced together with duration of hospitalization of the patients who underwent conventional LPN composed Group
patient. Moreover, the cold cutting during the B. Concerning Group A, lesion size at Computed Tomography
enucleoresection of the lesion get nearer to the pseudocapsule scan (CT-scan) was 2.35+1.10 cm, operative time
of the tumour to treat. This feature could reduce the number 133.53+40.54 min and Estimated Blood Losses (EBL)
of nephrons removed and so the kidney damage. Moreover 201.46+109.81 mL. Results of this technique were thus
the reduction of this peri-tumoral tissue does not impair the compared with the results of conventional LPN: Groups were
oncological effectiveness of the procedure. comparable about preoperative data except for CT-scan size
(2.35+1.10 vs. 3.19+1.57, Group A vs. B, respectively,
1 Minervini A, Di Cristofano C, Lapini A, Marchi M, Lanzi p=0.0029). On the contrary, no differences were recorded in
F, Giubilei G et al: Histopathologic Analysis of Peritumoural terms of PADUA 1 score (3). Concerning perioperative data,
Pseudocapsule and Surgical Margin Status after Tumour warm ischemia time (WIT) was 0 min in all Group A cases;
Enucleation for Renal Cell Carcinoma. Eur Urol 55(6): mean WIT in Group B was 20.90+9.27 min (p<0.0001);
1410-1418, 2009. operative time (133.53+40.54 vs. 120.59+32.33, A vs. B,
2 Ficarra V, Novara G, Secco S et al: Preoperative aspects and respectively) and EBL (201.46+109.81 vs. 164.27+128.68, A
dimensions used for an anatomical (PADUA) classification vs. B, respectively) were slightly higher in Group A even if
of renal tumours in patients who are candidates for nephron- these differences did not reach statistical significance
sparing surgery. Eur Urol 56: 786-793, 2009. (p=0.0763 and p=0.1464, respectively). One case (2.4%) in
3 Moch H, Artibani W, Delahunt B, Ficarra V, Knuechel R, Group A (central tumour) was converted to conventional LPN.
Montorsi F et al: Reassessing the Current UICC/AJCC No differences were noted between the two Groups neither in
TNM Staging for Renal Cell Carcinoma. Eur Urol 56: 636- terms of intra- nor post-operative complications. Similarly,
643, 2009. positive surgical margins’ rate and thickness of peri-tumoural

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

healthy tissue excised were not statistically different. Finally, 2Fisica

Medica, Istituto Nazionale Tumori Regina Elena –
concerning functional results, we did not find any differences IFO, Roma, Italy
when comparing pre-operative and post-operative SCr and
eGFR in both Groups, even if a trend towards a more relevant Aim: There is evidence that higher doses are usually related
post-operative worsening of eGFR was observed in Group B to higher biochemical control also in patients treated for
with respect to Group A (p=0.0445). Discussion and salvage radiotherapy (1). To reduce the irradiated volume,
Conclusion: Notwithstanding the limits of the study, our based on the experience of contouring intraprostatic lesions
results suggest that cl-LPN is an emerging alternative to on magnetic resonance imaging (MRI) with spectroscopy (2)
conventional LPN that could be a new surgical option when and 18F – choline PET-CT (3), in our study nodal recurrences
approaching small renal masses. By this approach kidney does were indentified also with this modalities. Acute toxicity in
not undergo ischemia and this, reasonably, limits renal damage patients treated with salvage intensity-modulated radiation
without significant increase of blood losses and complications therapy (IMRT) with simultaneous integrated boost (SIB) in
or impairment of pathological results. In our opinion, it is recurrences after radical prostatectomy will be reported.
essential that the surgeon had significant laparoscopic Materials and Methods: Between February 2009 and
experience before embarking on this kind of procedure, February 2012, 34 men with rising PSA identifying nodular
especially for the most challenging cases. recurrences in the prostatic bed using magnetic resonance
imaging (MRI) with spectroscopy and 18F – choline PET-CT
1 Gill IS, Eisenberg MS, Aron M et al: Zero Ischemia Partial were evaluated. Median age of patients was 69 years (range
Nephrectomy: Novel Laparoscopic and Robotic Technique. 48-80) with mean PSA at the beginning of radiotherapy
Eur Urol 59: 128-134, 2011. equal to 2.55 ng/ml (range 0.11-4.98). Treatment plans were
2 Go AS, Chertow GM, Fan D et al: Chronic kidney disease designed by using a five or seven field sliding window
and the risks of death, cardiovascular events, and intensity modulated technique (IMRT) to administer an
hospitalization. N Engl J Med 351: 1296-1305, 2004. EQD2Gy (considering an α/β value of 1.5 Gy for prostate
3 Ficarra V, Novara G, Secco S et al: Preoperative aspects and cancer) as simultaneous integrated boost (SIB) to the nodular
dimensions used for an anatomical (PADUA) classification recurrences (range 73 Gy-85 Gy) and to the prostatic bed
of renal tumours in patients who are candidates for nephron- (range 64 Gy-79 Gy), 8 pts (24%) were also simultaneously
sparing surgery. Eur Urol 56: 786-793, 2009. irradiated on the pelvic nodes (range 45 Gy-51 Gy).
Treatments were delivered by a Varian Linac (2100 CD)
equipped with the Millennium multileaf collimator (120
75 leaves). 18 pts (53%) underwent androgen deprivation
HIGH-DOSE SALVAGE SIMULTANEOUS therapy (ADT). Acute toxicity was evaluated weekly during
BOOST WITH INTENSITY-MODULATED treatment using the CTCAE scale vers.4 supplemented by an
RADIOTHERAPHY FOR RECURRENCES AFTER in-house-developed scoring system. Results: No grade 3 or
RADICAL PROSTATECTOMY: ACUTE TOXICITY 4 acute gastrointestinal toxicity was developed. The
percentage of patients who experienced toxicities are
Maria Grazia Petrongari1, Biancamaria Saracino1, Valeria
reported in the table. Discussion and Conclusion: The results
Landoni2, Anna Maria Ferraro1
of our study indicate that SIB delivered with IMRT in the
1Radioterapia Oncologica, Istituto Nazionale Tumori Regina rescue of patients with recurrent nodules of prostate cancer
Elena - IFO; after radical prostatectomy is well tolerated and allows to

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

administer high doses to the disease with a reasonable rate or 2 Gy per fraction. We proceeded with plan optimization and
of acute toxicity. DVH evaluation. We evaluated acute and late gastrointestinal
(GI) and genitourinary (GU) toxicities. Moreover, relapse rate,
1 Goenka et al: Long-Term out comes after high-dose post metastasis rate, Disease Free Survival (DFS) and Overall
prostatectomy salvage radiation therapy. Int J Radiation Survival (OS) were calculated. Results: Median follow-up was
Oncology Biol Phys, 2012, in press. 36 months with last controls performed in December 2011.
2 Fonteyne et al: Intensity-modulated radiotherapy as primary Acute toxicity was mainly digestive, 67.8% of patients
therapy for prostate cancer: report on acute toxicity after presenting moderate nausea and vomiting. No late GU or GI
dose escalation with simultaneous integrated boost to toxicities were noticed. No local relapse and no distant
intraprostatic lesion. Int J Radiation Oncology Biol Phys metastases were observed. Only one patient experienced
72(3): 799-807, 2008. controlateral testicular cancer and he was successfully treated
3 Pinkawa et al: Dose-escalation using intensity-modulated with surgery. DFS and OS was 100% since all patients were
radiotherapy for prostate cancer -Evaluation of the dose alive in complete remission at last control. Discussion and
distribution with and without 18F-choline PET-CT detected Conclusion: Modern management of stage I testicular cancer
simultaneous integrated boost. Radiotherapy and Oncology has changed over last years. Our study showed that PART
93: 213-219, 2009. represents a valid option for stage I testicular seminoma. Acute
toxicity is dominated by moderate gastro-intestinal side-effects
but PART provides excellent results in terms of local control
76 and survival.
ADJUVANT PARA-AORTIC RADIOTHERAPY
FOR STAGE I TESTICULAR SEMINOMA:
OUR EXPERIENCE 77
VALIDATION OF PRIAS ACTIVE SURVEILLANCE
Girolamo Spagnoletti1,
Rita Marchese2,Anna Maria Leo2,
CRITERIA IN PATIENTS SUBMITTED
Grazia Nardella2, Maria Enfasi2, Giuseppe Bove2
TO RADICAL PROSTATECTOMY
1StrutturaComplessa di Radioterapia Azienda Ospedaliero,
Cosimo Bizzarri1, Riccardo Schiavina1, Giovanni Passaretti1,
Universitaria Ospedali Riuniti, Foggia;
2Radioterapia, Ospedali Riuniti, Foggia, Italy Daniele Romagnoli1, Alessandro Bertaccini1,
Eugenio Brunocilla1, Fabio Manferrari1, Sergio Concetti1,
Marco Garofalo1, Francesco Chessa1, Lorenzo Bianchi1,
Introduction and Aim: Testicular germ cell tumors represent
Michele Provenzale1, Rizzi Simona1,
the most common solid cancer in males between 20 and 40
Michelangelo Fiorentino2, Giuseppe Martorana1
years of age and the majority of patients present with clinical
stage I disease and approximately 40% to 60% are pure 1Department of Urology, S. Orsola-Malpighi Hospital,
seminomas. Surgery remains the most important therapy for University of Bologna;
this kind of neoplasm and present management of testicular 2Anatomia e Istologia Patologica – Grigioni, AOU S. Orsola

seminoma can achieve excellent survival rates, in the order of Malpighi, Università di Bologna, Italy
97-100%. Some years ago standard adjuvant management has
been extended-field radiotherapy after radical inguinal Objective: The aim of this study was to evaluate the
orchidectomy. During the last years alternative management pathological characteristics of a cohort of patients submitted to
strategies, including surveillance and para-aortic lymph node radical prostatectomy in presence of presumed indolent
only radiotherapy (PART) have been explored. Our work aims prostate cancer according to the Van den Bergh’s criteria
to evaluate efficacy and toxicity of PART for stage I testicular described for the Prostate Cancer Research International Active
seminoma after surgry. Materials and Methods: Twenty-eight Survelliance (P.R.I.A.S.). Patients and Methods: We considered
patients with stage I pure seminoma were treated with PART 1800 patients treated with RP between January 2003 and
at Radiotherapy Department in Foggia between January 2007 January 2012. All the patients had their biopsy and RP
and December 2010. Median age was 33 years (range between specimen evaluated in our institute. Among these patients, we
25 and 44 years). After histological diagnosis all patients identified 114 men (1%) who fulfilled the inclusion criteria for
underwent orchidectomy. No patient received chemotherapy. the AS of P.R.I.A.S. defined by Van Den Bergh (PSA<10; <=2
In order to deliver radiotherapy treatment, Computed positive core, >=10 biopsy core and Gs=6 o 3+4). A single
Tomography scans were obtained to contour Clinical Target experienced uropathologist reviewed the biopsy core and the
Volume, Planning Target Volume and organs at risk. PART RP specimen according to the 2009 International Society of
was administered 4-6 weeks after surgery with a median total Urological Pathology (ISUP) protocol. After pathological
dose of 21 Gy (range between 20 and 25.2 Gy) with 1.5, 1.8 revision, only 60 out of 114 (53%) fulfilled the pathological

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

characteristics mentioned above. Results: Among our 60 stratified according to academic status and hospital
patients, 58 had organ confined disease (8 pT2a: 13%, 6 nephrectomy volume (high >300, intermediate 100-300, low
pT2b:10 %, 41 pT2c: 68%) while 2 patients had extracapsular <100 nephrectomies in the study period). Trends in the use of
invasion (pT3a: 3%), though no seminal vescicle involvement PN were assessed overall and according to institution type.
(pT3b) was detected in this cohort. In 50 cases (83%) the Results: The overall number of surgical procedures for renal
resection margins were free from cancer (R0), while 10 cases tumors performed in Piedmont region increased significantly
(17%) showed positive margins (R1). The pathological Gs was from 2000 to 2010 (+27%). RN is the preferred surgical
6 in 18 cases (30%), 3+4 in 27 (45%), 4+3 in 14 (23%) and 8- treatment, but an increasing use of PN was observed over the
10 in 1 (2%). According to the risk based analysis, 45 patients study period. This trend is more significant in centres with
(75%) were at low risk of aggressive disease, while the high renal surgical volume (+ 19.9%) and in non academic
percentage of intermediate risk patients was about 23%, and centres (+13.7%). Discussion and Conclusion: PN is
only 1 patient (2%) harboured a high risk prostate cancer. increasingly performed in the last decade in Piedmont region.
Conclusion: According to our study, the inclusion criteria of The most significant increase in the indications to NSS was
Prostate Cancer Research International Active Survelliance observed in institutions with high renal surgical volume.
(P.R.I.A.S.) have high accuracy in the prediction of organ However, PN remains relatively underused and strategies to
confined and low-intermediate risk prostate cancer. Our results enhance conservative treatments of renal tumors should be
seem to be consistently better than those of the actual literature, implemented.
maybe thanks to the anatomopathological review performed by
a single experienced uropathologist, which allowed us to
exclude 53 patients who would have compromised the accuracy 79
of our results. Thus, according to our experience, the actual FLUORESCENT CYSTOSCOPY WITH
Active Surveillance parameters can be safely adopted, only if HEXAMINOLEVULINATE: DIAGNOSTIC
the review is performed by a single uropathologist of proven ACCURACY FOR NON MUSCLE
experience. INVASIVE BLADDER CANCER
Alessandro Volpe, Davide Giraudo, Paolo De Angelis,
Elisa De Lorenzis, Monica Zacchero, Paolo Mondino,
78
Francesco Varvello, Filippo Sogni, Carlo Terrone
TRENDS IN PARTIAL NEPHRECTOMY
USE IN ITALY: DATA FROM PIEDMONT Clinica Urologica, Università del Piemonte Orientale,
REGION IN THE LAST DECADE Ospedale Maggiore della Carità, Novara, Italy
Alessandro Volpe, Paolo De Angelis, Michele Billia,
Introduction: The sensitivity of white light cystoscopy (WLC)
Antonia Di Domenico, Luisa Zegna, Paolo Mondino,
can be improved especially for the detection of flat urothelial
Irene Mittino, Elisa De Lorenzis, Carlo Terrone
neoplasms. Fluorescent or blue light cystoscopy (BLC) has the
Clinica Urologica Università del Piemonte Orientale - potential to overcome the limitations of WLC. Aim of this
Ospedale Maggiore della Carità, Novara, Italy study was to compare the diagnostic accuracy of WLC and
BLC in the diagnosis of urothelial cancer and to identify the
Introduction: Recent studies have shown that partial conditions where BLC can provide the highest diagnostic
nephrectomy (PN) has equivalent oncologic outcomes with advantage over WLC. Patients and Methods: 71 patients with
radical nephrectomy (RN) for localized renal tumors. The a suspicious primary or recurrent bladder tumor were enrolled
most recent international guidelines for renal cell carcinoma in the study. Patients who had intravesical instillations in the 3
(RCC) recommend the use of nephron sparing surgery (NSS) months before the procedure were not eligible. After
for renal lesions up to 7 cm in size whenever technically intravescical instillation of Hexaminolevulinate 85 mg one
feasible. Despite this, PN remains underused in North hour before the procedure, the patients underwent WLC
America. Aim of this study was to evaluate trends in PN use followed by BLC. All observed lesions were reported in a
during the last decade in a north-western Italian region. diagram, biopsied or resected. Detection rate and false
Patients and Methods: The regional archives of hospital detection rate of the two techniques were compared. Data
discharge records in Piedmont region from January 2000 to were stratified according to pathology of bladder lesions and
December 2010 were retrospectively analysed. All procedures bladder site where the lesions were observed. A subset
recorded with the ICD-9 codes 55.3, 55.4 (PN) and 55.5 (RN) analysis was also performed to assess the diagnostic accuracy
performed for a primary diagnosis of renal tumor (189.0) were of WLC and BLC in patients who had (n=36) or had not
included in the analysis (n=6180). The surgeries were (n=35) undergone previous intravesical treatments to prevent
performed in 43 different urological institutions, that were recurrence and progression. Results: Overall 270 bladder

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

lesions were detected (102 with BLC, 7 with WLC, 161 with the Friuli Venezia Giulia region (FVG), northeastern Italy.
both techniques). At pathology 236 lesions were malignant, Methods: PC cases were identified through the population-based
while 34 were benign. The detection rate was 62.2% for WLC Cancer Registry that collects all cancer cases occurring since
(147/236) and 98.3% for BLC (232/236). The highest 1995 in resident people. Individual history of PSA testing was
diagnostic advantage for BLC was observed for the diagnosis extracted from the regional digital health archive that provides
of carcinoma in situ and for lesions located at the bladder the identification of men tested for PSA and the date of testing.
dome. The false detection rate was 12.5% for WLC (21/168) Joinpoint regression analysis was used to identify significant
and 11,4% for BLC (30/263). Overall, 32/71 patients (45.1%) changes over time in log-linear slopes. The annual percentage
had a diagnostic advantage with BLC (diagnosis of at least change (APC) was computed by means of generalised linear
one Cis, dysplastic or papillary lesion that was missed at models. Results: From 1998 to 2007, 10377 incident PC cases
WLC). The subset analysis showed that the detection rate of have been identified, of which 56.5% were among elderly. The
BLC is not decreased in patients who have undergone previous crude incidence rate of PC in elderly men increased from
endovesical treatment (98.1% vs. 97.8%), as well as the false 824.2/100.000 in 1998 to 875.4 in 2007, with an APC of +6.18
detection rate is not increased (11.6% vs. 11.4%). Discussion (95%CI 2.01-3.16). 38.826 men (out of the approximately
and Conclusion: BLC is a promising technique that has a 70300 elderly men residing in FVG) were tested for PSA in
significantly higher detection rate than WLC. The highest 2009, with a total number of 58147 tests performed. Between
diagnostic advantage with BLC can be obtained for the 1998 and 2009, the percentage of elderly men aged 70-79 who
diagnosis of Cis and of lesions located at the bladder dome. underwent PSA test increased substantially (APC=13.02%),
The detection rate of BLC is not decreased in patients who with a change in slope in 2002. Among elderly men aged 80
underwent previous endovesical treatments when the last years or older, the APC increase was 12.80%, and 2003 the year
instillation is not performed in the 3 months before the with the change in slope. Approximately 30% of elderly men
procedure. who underwent PSA were tested more than once. On average,
there were 1.06 cases of newly diagnosed PC every 100 PSA
tests. The number of elderly men tested for PSA who underwent
80 ecographic examination and/or biopsy strongly declined -from
PROSTATE SPECIFIC ANTIGEN (PSA) USE AND 900 to 400 ecographic exams for every 10000 tested men; from
INCIDENCE OF PROSTATE CANCER (PC) AMONG 300 to 200 biopsy for every 10000 tested men. Conclusion: The
ELDERLY MEN IN NORTH-EAST ITALY: A increasing incidence of PC in FVG reflects the rising use of
POPULATION-BASED EVALUATION STUDY PSA testing also among elderly men, even for men aged 80
years or older. The huge number of PSA tests was inversely
Diego Serraino1, Sivia Birri2, Lucia Fratino3,
associated with the number of ecographic examinations or
Ettore Bidoli2, Emilia De Santis2, Ornella Forgiarini2,
biopsies over the study period, indicating that PSA testing is
Roberto Bortolus4, Loris Zanier5
widely used in asymptomatic elderly men.
1Epidemiologia, IRCCS Centro di Riferimento Oncologico,
Aviano;
2Epidemiologia, IRCCS CRO, Aviano; 81
3Clinica di Oncologia Medica, IRCCS CRO, Aviano; CONTRAST-ENHANCED ULTRASOUND FOR
4Radioterapia IRCCS CRO, Aviano; EVALUATION OF RCCS: IDENTIFICATION OF
5Anatomia e Citoistologia Patologica, Direzione Centrale HIGH-RISK TUMORS THROUGH SIGNAL
FVG, Italy TIME/INTENSITY CURVES
Federico Lanzi1, Elena Bertelli2, Claudia Giannessi1,
Purpose: The PSA blood test has changed the epidemiology of
Giancane Saverio1, Antonella Verrioli2, Lorenzo Masieri1,
PC, creating a dramatic rise in its incidence and helping to shift
Livia Eleonora Quattrone2, Arcangelo Sebastianelli1, Andrea
the stage of disease to much earlier and potentially more curable
Moffa Marchetti1, Alberto Lapini1, Simone Agostini2
one. PSA testing remains, however, a source of uncertainties
since periodic testing may increase the risk of treating many 1Clinica Urologica [I] AOU Careggi, Firenze;
men for screen-detected PC who would not have experienced 2Dipartimento Di Radiodiagnostica AOU Careggi, Firenze,
ill effects if PC had been left undetected. The risk of over Italy
diagnosis and over treatment associated with PSA is particularly
significant among elderly men, among whom it is questioned Aim: The aim of the study is to evaluate the efficacy of
whether life expectancy is significantly reduced after PC time/intensity curves (T/IS) for quantitative analysis of
diagnosis. The study aim was to assess, from 1998 thru 2009, contrast kinetics during contrast-enhanced ultrasound (CEUS)
PSA use and PC incidence rates in elderly men (>= 70 years) in in characterization of renal lesions. Patients and Methods: We

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

prospectively evaluated 85 renal lesions with CEUS. A Background: High-very high-risk(cT3, N1, PSA ≥20 ng/ml
quantitative analysis of enhancement was performed using a and/or Gleason score ≥8, prostate cancer patients (pts) have a
dedicated software (QONTRAST, manufactured by Esaote for 5-years biochemical failure rate, after surgery or radiation,
Bracco Group) which elaborates colorimetric maps and over 50%. Neoadjuvant, concomitant and adjuvant
process Time/Intensity (T/IS) curves on region of interest hormonotherapy (HT) are currently the only systemic
(ROI). Of the evaluated lesions, 38 underwent surgery and 47 treatments with escalation dose of radiation therapy. Because
were addressed to the active surveillance regimen due to lesion of the heterogeneity of prostate cancer cells and the desire to
features and patients’ performance status. Our study improve the outcome with radiotherapy (RT), weekly
incorporates the histopathologically-confirmed lesions and the chemotherapy (CT) during RT in localized, high-risk prostate
21 of the 47 in surveillance with an available follow-up ≥2 cancer is being explored. Docetaxel has demonstrated
years. The kinetic of perfusion has been classified into 4 significant antitumor effect and impact on survival in
patterns: type I “rapid wash-in, slow wash-out”, type II “rapid hormone-refractory prostate cancer and a strong sensitization
wash-in and wash-out”, type III “slow wash-in and wash-out”, of tumor cells to radiation injury. Patients and Methods: From
type IV “slow wash-in, rapid wash-out” Results: Lesions with 2005 to 2010, 30 very high-risk pts were treated with high
type I pattern resulted clear cell RCCs (cRCC) Fuhrman G3 dose of RT and concomitant docetaxel. All pts had clinically
in 9/12 cases and cRCCs G2 with elevated cystic component (13/30) or pathologically (17/30) advanced disease. Clinically
in 3/12; 14 G2 cRCC and 2 cystic G1 cRCCs demonstrated Advanced Tumor (CAT):median age 73 years (range 65-81);
type II curves; type III curves in 4 G1 cRCCs, 1 G2 cRCC and Gleason score:7 in 1, 8 in 4, 9 in 7 pts and 10 in 1 case; PSA
3 papillary G2 RCCs (pRCC); 1 G2 pRCC and 1 cystic G2 median at Diagnosis was 9.3 (5.27-71.3) and PSA prior to
cRCC with pattern type IV. The 7 centrimetric solid lesions RT was 0,51 ng/ml (0.05-3.83); RT median dose was 80 Gy
and 14 cystic lesions in “active surveillance” regimen, all (range 76-80). Pathologically Advanced Tumor (PAT):
characterized by perfusion patterns III and IV appeared median age 65 years (range 57-80); Gleason Score: 8 in 4
dimensionally stable at a minimum follow-up of 2 years. and 9 in 13 pts; pT2c in 2, pT3a in 3, pT3b in 10 and pT4 in
Overall, Fuhrman G3-G2 tumors showed distinctive T/IS 2 pts; Nodes were positive in 3 pts; 6 pts were R1. PSA
curves (type I-II) with higher peaks of enhancement while for median at diagnosis, was 18 (4.25-56.3), PSA prior to RT
type III and IV curves, an ovelapping between stable lesions was 0.65 ng/ml (0.01-4.22); RT median dose, was 70 Gy
seems to exist, benign tumors and low-risk evolutive lesions. (range 66-76). Docetaxel was administered at a standard
With regards to the small series, the T/IS curves showed a weekly dose (30 mg for pts with surface area <2 m2 and 40
sensibility of 92.8% and a specificity of 80%. Conclusion: mg for pts with ≥2 m2). The median cycle of CT was 7
Contrast-enhanced ultrasound can be useful to better define (range: 2-8). All pts began HT before and during RT and
renal lesions both in patients undergoing surgery and in cases continued the treatment for 2 years after RT. Results: At
suitable to an “active surveillance” regimen. Time/intensity median follow-up of 36 months (8-60), 6 pts (20%) had
curves for quantitative analysis of contrast kinetics may help progression disease, (median period of recurrence: 14
in distinguishing biologically aggressive RCCs from months). Toxicity: gastrointestinal grade I was referred by
benign/low-risk tumors. Wider series may conduce to a more 18/30 and urological grade I by 12/30 pts. Two patients
accurate predictivity of T/IS curves regarding histological stopped CT after two cycles for systemic toxicity.
pattern. Discussion: During the same period in the same institution
139 pts with the same pathological characteristics were
treated with standard therapy: 42 with adiuvant RT+HT and
82 97 with radical RT+[Link] median follow-up of 29 months,
RADIOTHERAPY AND CONCOMITANT 33% of pts had a relapse. Conclusion: These preliminary
DOCETAXEL IN HIGH RISK PROSTATIC data confirmed the feasibility and the tolerability of weekly
CANCER:GUONE (NORTH EAST URO docetaxel in combination with RT in men at high risk of
ONCOLOGY GROUP) EXPERIENCE disease progression. No patient suffered performance status
worsening during the scheduled treatment. At a median
Roberto Bortolus1, Andrea Guttilla2, Fabio Zattoni2,
follow-up of 36 months, only 20% of pts had relapse disease
Lucia Fratino3, Antonio Garbeglio4, Mauro Arcicasa1,
and this was a remarkable result, considering that the patients
Mauro Trovò1, Filiberto Zattoni2
were at very high risk and with the standard treatment the
1Radiotherapy Oncology National Cancer Institute, Aviano global relapse was 33%. For such very high-risk patients,
PN; multimodal treatments combining HT, CT and RT will,
2Urologic Clinic University of Padua; possibly, be the treatment of choice in the future; however, at
3Oncology Department National Cancer Institute Aviano P; the moment, such treatments are only available in clinical
4Urology Department General Hospital Pordenone, Italy trials and patients should be encouraged to participate in them.

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

83 due to the need of complementary chest evaluation. SPLIT-

SPLIT-CT AND STANDARD CT-UROGRAPHY: CT showed a high sensibility for TCC and renal
A TAILORED-IMAGING FOR RENAL parenchymal pathologies and allowed a contextual
AND TRANSITIONAL CANCER representation of vessels, parenchyma and excretory
system. Moreover, in our series, SPLIT-CT seemed to have
Federico Lanzi1, Claudia Giannessi1, Elena Bertelli2,
a higher diagnostic value in case of uretheral malignancies,
Lorenzo Masieri1, Linda Calistri2, Saverio Giancane1,
representing the minus in lumen and the tumoral
Paolo Camilli2, Michele Lanciotti1,
vascularization. The limit of the procedure was represented
Andrea Moffa Marchetti1, Alberto Lapini1, Simone Agostini2
by a higher dose of contrast infused that should be
1Clinica Urologica [I] AOU Careggi, Firenze; considered in patients with renal failure. Conclusion:
2Dipartimento di Radiodiagnostica AOU Careggi, Firenze, SPLIT technique allows a detailed study with a dosimetric
Italy reduction up to 50%, becoming fundamental in terms of
cumulative dose in patients requiring long-term follow-up,
Introduction and Objectives: The gold standard in specially young and female patients. Our pilot study
evaluating urinary system is represented by CT-urography underlines the need of multicenter randomized trials to
performed as a single bolus of organoiodate contrast and 4 define an operative algorithm integrating standard CT-
acquisition phases (SBT-CT). The multibolus bi-triphasic urography and multibolus SPLIT technique.
technique (SPLIT-CT) demonstrated a diagnostic value
equivalent to standard CT, reducing radiation exposure in
extraurological pathologies. The aim of this study was to 84
propose the personalization of Uro-CT performed as a SBT- IDENTIFICATION OF FUNCTIONALLY ACTIVE
CT or a SPLIT-CT and to define the indications to these COPY NUMBER VARIANTS ASSOCIATED WITH
techniques. Patients and Methods: From January 2008 to PROSTATE CANCER RISK
December 2011 we performed 1536 CTs: every exam has
Francesca Demichelis
been tailored depending on the pathology and patient’s
performance status. Overall, 975 patients (63.5%) Tyrol-Weill Cornell-Harvard Consortium
underwent SBT-CT and 561 (36.5%) underwent SPLIT-CT.
CTs always started with an unenhanced panoramic view Introduction and Background: Prostate cancer is a leading
that addressed the radiologist in tailoring the examination. cause of cancer death in males throughout the world and
SPLIT-CT consisted of a first 70 mL contrast bolus and, if demonstrates the largest estimated effect of heritability
necessary, an arterial acquisition phase 25-30 seconds after among the most common tumor types as determined by a
the first injection; after 7 minutes a 50 mL contrast bolus Scandinavian twin-based registration study (1). Emerging
was injected, followed by a third bolus (50mL) 45 seconds insights into the genetics of constitutional disease etiology
later. Combined phase acquisition was usually performed demonstrate that germline polymorphisms in the form of
25-30 second after the last bolus. The CTDose (National Copy Number Variants (CNVs) are associated with diseases
Board of Health, Denmark) algorithm was used to calculate including cancer. In order to explore for CNVs associated
the effective radiation dose of the techniques. Every exam with prostate cancer, we examined 1,903 men from the Tyrol
was reviewed by a single dedicated uroradiologist. Results: Early Prostate Cancer Detection Program (2). Materials and
SPLIT infusion technique applies 170 mL of organoiodate Methods: The Tyrol cohort is a population-based prostate
contrast versus mean (range) 120 (100150) mL of SBT-CT. cancer screening program started in 1993 that intended to
Mean dosimetric levels of bi-triphasic SPLIT technique and evaluate the utility of intensive PSA screening in reducing
SBT-CT were: 12.7(r: 6-18), 20.8(r: 10-30) and 25.4(r: 12- prostate cancer specific death. We profiled peripheral blood
38) mSv respectively. We performed the SPLIT-CT in case samples using a high resolution short oligonucleotide
of micro/macrohaematuria, with positive urinary cytology platform and characterized over 5,000 CNVs using IgC2N,
and/or positive FISH test without previous diriment a computational framework (3). Results: We queried low-
ultrasonography (US) and cystoscopy, hydronephrosis with frequency bi-allelic CNVs from 1,903 men of Caucasian
previous non concluding US, to evaluate and follow-up origin and discovered two CNVs strongly associated with
urothelial tumors, in preoperatory staging of patients with prostate cancer risk. The first risk locus (p=7.7×10–4, Odds
muscle-invasive bladder tumors. SBT-CT was performed in Ratio (OR)=2.78) maps to 15q21.3 and overlaps a non-
patients with large reno-urothelial tumors and adbominal coding enhancer element that contains multiple AP-1
lesions of uncertain interpretation at US or discovered transcription factor binding sites. Chromosome conformation
during preliminary not enhanced CT, in follow-up of renal capture (Hi-C) data suggested direct cis interactions with
masses after surgery and in preoperative plannig of RCCs distant genes. The second risk locus (p=2.6×10–3, OR=4.8)

1900
 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

maps to the Alpha-1,3-mannosyl-glycoprotein 4-beta-N- tumor with a neoplastic thrombus (NT) extended from the
acetylglucosami-nyltransferase C (MGAT4C) gene on right renal vein to all inferior vena cava (IVC) and to the
12q21.31. In vitro cell line assays found this gene to right atrium (RA). The thrombus partially involved the right
significantly modulate cell proliferation and migration in supra hepatic veins and the left renal vein. Distant
both benign and cancer prostate cells. Further, MGAT4C was metastases were not detected. Results: Through a
significantly overexpressed in metastatic versus localized laparotomic median incision, the urological equipe
prostate cancer. These two risk associations were replicated mobilised the right colon and exposed the right kidney. The
in an independent PSA-screened cohort of 800 men renal vascular pedicle was exposed and the radical
(15q21.3, combined p=0.006; 12q21.31, combined p=0.026). nephrectomy with adrenalectomy was performed. The right
Discussion: These findings establish non-coding and coding and left renal veins, that were obstructed by NT, were
germline CNVs as significant risk factors for prostate cancer isolated. The liver was mobilized to allow the exposition
susceptibility and implicate their role in disease development of the intra and supra hepatic VCI, completely occupied
and progression. In summary, this is the first large scale, by the NT. Sternotomy and pericardiotomy were
unbiased study using this patient population to study the performed by the heart surgery equipe. Aortic arch,
contribution of germline CNVs towards prostate cancer risk. superior VC and the VCI just above iliac veins were
Conclusion: We envision that CNVs can eventually be used cannulated. On normothermic CBP and beating heart,
to assess patient risk for aggressive prostate cancer at time right atriotomy and a “J” incision on VCI were
of diagnosis. simultaneously performed. At the same time, the
urologists and heart surgeons removed the NT from the
1 Lichtenstein P et al: Environmental and heritable factors in RA, the left VR and the VCI. Part of the VCI wall was
the causation of cancer – analyses of cohorts of twins from infiltrated by the thrombus and was resected. RA and VCI
Sweden, Denmark, and Finland. N Engl J Med 343(2): 78- were closed and the patient was weaned from CBP. CPB
85, 2000. time: 91 min; Surgical time: 6 hrs. Estimated blood loss
2 Bartsch G et al: Tyrol Prostate Cancer Demonstration 500 ml. Autologous blood transfusion: 700 ml.
Project: early detection, treatment, outcome, incidence and Pathological report: clear cell RCC pT3c Fuhrman G3
mortality. BJU Int 101(7): 809-816, 2008. pN1. Intensive care stay: 5 days. Post operative in-hospital
3 Banerjee S et al: A computational framework discovers new stay: 7 days. A post-surgical transthoracal echocardiography
copy number variants with functional importance. PLoS One demonstrated regular parameters without any residual
6(3): e17539, 2011. thrombus in RA and normal cardiac function. One month
later, total body CT showed a regular VCI with no signs of
persistent disease. Conclusion: In our experience,
85 management of T3c kidney cancer with a beating heart
RADICAL NEPHRECTOMY AND normothermic CBP appears a feasible, safe and effective
CAVOATRIAL THROMBECTOMY ON technique. As neither hypothermia nor heart arrest are
NORMOTHERMIC CARDIOPULMONARY needed, our technique improves patient recovery and
BY-PASS AND BEATING HEART: A CASE REPORT diminishes risks of complications. Furthermore, with
AND DESCRIPTION OF THE TECHNIQUE cannulation of lower IVC, other vascular access for lower
venous return are not necessary.
Elena Strada1, Antonio Galfano1, Giovanni Petralia1,
Claudio Francesco Russo2, Luigi Martinelli2,
Aldo Massimo Bocciardi1
87
1Urologia Ospedale Niguarda, Ca’Granda, Milano; HORMONAL THERAPY PROMOTES HORMONE-
2Cardiochirurgia Niguarda, Ospedale Ca’Granda, Milano, RESISTANT PHENOTYPE BY INCREASING DNMT
Italy ACTIVITY AND EXPRESSION IN PROSTATE
CANCER MODELS
Objectives: Usually, cavoatrial kidney cancer is managed
Giovanni Luca Gravina1, Claudio Festuccia2,
with cardiopulmonary by-pass (CBP) with deep
Francesco Marampon2, Margherita Piccolella3,
hypothermia circulatory arrest (DHCA). In this study, we
Marcella Motta3, Luca Ventura4, Bianca Maria Zani5,
report the feasibility, safety and effectiveness of radical
Richard G. Pestell6, Vincenzo Tombolini7,
nephrectomy with cavoatrial thrombectomy on
Andrea Lenzi8, Emmanuele A. Jannini9
normothermic CPB and beating heart. Patients: A 71 years
old healthy woman presented with lumbar pain. Abdomen 1Dipartimento di Medicina Sperimentale, Università Di
US and following CT scan detected an 8 cm right renal L’Aquila Divisione di Radioterapia;

1901
 ANTICANCER RESEARCH 32: 1843-1966 (2012)

2Department of Experimental Medicine, Radiobiology 89

Laboratory, University of L’Aquila; THE VALUE OF BIOPSY LATERALITY IN
3Department of Endocrinology, Center of Endocrinological ASSOCIATION WITH PSA AND GLEASON SCORE
Oncology University of Milano; FOR THE IDENTIFICATION OF SUBJECTS AT HIGH
4Dipartment of Pathology San Salvatore RISK OF RECURRENCE IN PROSTATE CANCER
Hospital, L’Aquila,
5Department of Experimental Medicine University of Giovanni Luca Gravina1, Luca Ventura2, Mario Di Staso3,
Pierluigi Bonfili3, Cluadio Festuccia4,
L’Aquila, Italy;
6Department of Cancer Biology, Kimmel Cancer Center Marampon Francesco4, Vincenzo Tombolini5,
Andrea Lenzi6, Emmanuele A. Jannini7
Thomas Jefferson University, Philadelphia, PA, U.S.A.;
7Department of Radiological Sciences University Of Rome 1Department of Experimental Medicine University of Rome
“La Sapienza” Spencer-Lorillard Fondation, Rome; “La Sapienza”;
8Depertment of Experimental Medicine University Of Rome 2Department of Pathology, San Salvatore Hospital, L’Aquila,

“La Sapienza”; 3Division of Radiotherapy San Salvatore Hospital, L’Aquila,

9Course of Endocrinology And Medical Sexology, 4Department of Experimental Medicine, Radiobiology

Department Of Experimental Medicine University of Laboratory, University of L’Aquila;

L’Aquila, Italy 5Department of Radiological Sciences University of Rome

“La Sapienza;
We hypothesized that hormonal therapy favors the 6Depertment of Experimental Medicine University of Rome

development of the hormone-resistant phenotype through “La Sapienza;

epigenetic mechanisms. Human prostate cancer tissues and 7Course of Endocrinology and Medical Sexology,

in vitro and in vivo models were used to verify this Department of Experimental Medicine, University of
hypothesis. We demonstrated that tumor cells continuously L’Aquila, Italy
treated with bicalutamide (BCLT) or cultured in androgen-
depleted medium progressively acquire higher DNA Background: Predicting patients with prostate cancer (Pca) at
methyltransferase (DNMT) activity and expression than high risk of recurrence (HRR) is a major challenge for
cells cultured in standard condition. Increased DNMT clinicians. Clinical T-stage poorly predicts the pathological
expression and activity also paralleled the up-regulation of stage and understaging occurs in up to 60% of cases. Here we
truncated AR isoforms, which favors the development of determine if needle biopsy parameters improve the value of
the hormone-resistant phenotype. After androgen NCCN criteria for predicting men at HRR. Methods: A
stimulation with 12 10− M dihydrotestosterone, DNMT retrospective survey of 488 men who underwent RP was
activity was significantly reduced in comparison with undertaken. Univariate and multivariate logistic regression with
hormonal therapy. Consistent with these observations, the receiver operating characteristic (ROC) curves were generated
silencing of DNMT3a and DNMT3b significantly to test which parameters were able to best individulize men at
decreased the DNMT activity levels. These findings were HRR when histopathologic findings were used as the reference
also directly correlated with PTEN downregulation and standard. The parameters were: PSA, biopsy laterality, total
activation of ERK and PI3K/Akt pathways. The use of a number of positive biopsy cores, clinical T stage, and Gleason
pan-DNMT inhibitor (5Azacitidine) greatly reduced the score. The combination of best predictors then was compared
development of the hormone-resistant phenotype induced with the standard NCCN criteria in terms of ability to predict
by longterm BCLT treatment, and this finding correlated HRR. Results: At univariate analysis all clinical parameters
with low DNMT activity. The regulation of DNMT activity [biopsy laterality (OR=2.389; 95%CI 1.49 to 3.82; p<0.0001);
was, in some measure, dependent on the androgen Gleason score (OR=1.678; 95%CI 1.37 to 2.046; p<0.0001),
receptor, as small interfering RNA treatment targeting the total number of positive biopsy cores (OR=1.488; 95%CI 1.27
androgen receptor greatly decreased the modulation of to 1.74; p<0.0001) and PSA (OR=1.329; 95%CI 1.26 to 1.53;
DNMT activity under androgenic and antiandrogenic p<0.0001)] except the clinical T-stage (OR=1.136; 95%CI 0.86
stimulation. These observations were correlated in vivo in to 1.49; p=0.343) significantly predicted men at HRR. At
patients, as demonstrated by immunohistochemistry. multivariate analysis only biopsy laterality (OR=2.453; 95%CI
Patients treated by BCLT before surgery had higher 1.07 to 5.61; p=0.033), Gleason score (OR=1.847; 95%CI 1.38
DNMT3a and DNMT3b expression than patients who had to 2.46; p<0.0001) and PSA (OR=1.490; 95%CI 1.29 to 1.71;
not undergone this treatment. Our findings provide p<0.0001) were predictors of HRR. The association of PSA,
evidence of a relationship between the castration-resistant Gleason score and biopsy laterality achieved a significant larger
phenotype and DNMT expression and activity in human AUC (AUC=0.835; 95%CI 0.791 to 0.873; p<0.0001) than the
prostate cancer. association of standard parameters used in the NCCN criteria

1902
 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

(clinical T-stage, PSA and Gleason score) (AUC=0.685; 95%CI surgery and in the last years it is increasingly becoming a
0.630 to 0.736; p<0.0001) in the prediction of HRR. popular method in urology. Aim of our study was to evaluate
Conclusion: The biopsy laterality as replacement of clinical T the applicability of the modified Clavien classification system
stage contributes significantly to improve the value of NCCN (CCS). Patients and Methods: A consecutive series of patients
criteria for predicting subjects at HRR. with primitive or recurrent bladder cancer treated with radical
cystectomy from April 2011 to August 2011 at eleven
academic centres in Europe were evaluated for complications
90 occurring up to the end of the first postoperative month.
EVALUATION OF POSTOPERATIVE RADICAL Variables analyzed for each patient were: age, sex, asa score,
CYSTECTOMY COMPLICATIONS: A MODIFIED anticoagulation therapy, type of diversion, operation time,
CLAVIEN CLASSIFICATION SYSTEM ANALYSIS preoperative hydronefrosis and BMI All complications were
prospectively recorded and classified according to the
Cosimo De Nunzio1, C. Leonardo2, L. Cindolo3,
modified CCS. Results were presented as complication rates
A. Antonelli4, A. Brassetti5, A. Cantiani5, M. Cerasini5,
per grade. Chi-square and Kruskal Wallis tests and binary
C. Ceruti6, C. De Dominicis2, F. De Luca7, P. Destefanis6,
logistic regression analysis were used for statistical analysis.
V. Di Santo8, F. Esperto5, M. Falsaperla9, H. Fattahi5,
Results: 194 patients were prospectively enrolled. Mean age
M. Gallucci10, E.r. Gonzales11, R. Lombardo5,
was 57.8±12.7 years; mean BMI was 21.5±2.3 Kg/m2. Mean
M.a. Maestro11, G. Maugeri9, A. Minervini12,
bladder tumors size was 3.6±3.7 cm, mean number of bladder
V. Pagliarulo13, P. Parma7, S. Perdonà14, A. Porreca8,
lesions was 2±2. All patients underwent radical cystectomy.
R. Rocco15, L. Schips3, S. Serni2, M. Serrago15,
Urinary diversion consisted in orthotopic neobladder in 44
C. Simeone4, G. Simone10, R. Spadavecchia13,
patients (23%), ileal conduit in 89 patients (46%) and
C. Terrone16, A. Tizzani6, A. Tubaro5
ureterocutaneostomy in 61 patients (31%). Mean operative
1Urologia, Azienda Ospedaliera Sant’Andrea; time was 307±55 minutes. Mean hospital stay was 14.5±2.4
2Dipartimento di Urologia, Università” La Sapienza” days. 185 complications were recorded in 123 patients.
Policlinico Umberto I˚, Roma; Overall perioperative morbidity rate was 63%. Most of them
3Dipartimento di Urologia, Ospedale Padre Pio Da were not serious and were classified as Clavien type I (51
Pietrelcina, Vasto; cases; 27.5%) or II (91 cases, 49%). Higher grade
4Dipartimento di Urologia, Clinica Urologica, Università di complications were observed: Clavien type IIIa in 15 cases
Brescia, Brescia; (8%), IIIb in 18 cases (10%); IVa in 5 cases (3%), IVb in 2
5Dipartimento di Urologia, Università” La Sapienza” cases (1%) and V in 3 cases (1.5%). Reoperation rate was 8%
Azienda Ospedaliera Sant’Andrea, Roma; (16 patients) for severe wound infection (4 patients), urinary
6Dipartimento di Urologia, Presidio Ospedaliero Le anastomosis leakage (4 patients) and ileal perforation or
Molinette, Torino; occlusion (7 patients). Patients who underwent ileal conduit
7Dipartimento di Urologia, Ospedale Fatebenefratelli Ed urinary diversion presented a higher rate of CCS type I
Oftalmico, Milano; complications (58%) when compared to other urinary
8Dipartimento di Urologia, Policlinico di Abano, Abano diversions (p=0.034). No significant association was found
Terme; between Age, BMI, ASA score, anti-coagulant treatment,
9Dipartimento di Urologia, AOU Policlinico Vittorio preoperative hydronephrosis, operative time, hospital stay and
Emanuele, Catania; CCS type I or ≥IIIb complications. Patients with CCS
10Dipartimento di Urologia, IFO Regina Elena, Roma, Italy; complications type II and IIIa presented a significant longer
11Dipartimento di Urologia, Hospital Universitario Infanta operative time and hospital stay in univariate and multivariate
Sofia, Madrid, Spain; analysis (p=0.01) (Table I).
12Dipartimento di Urologia, Ospedale Careggi, Università di

Firenze, Firenze; Table I.

13Dipartimento di Urologia, Università di Bari, Bari;
14dipartimento di Urologia, Istituto Nazionale Tumori, CCS type II CCS type IIIa
Fondazione G Pascale, Napoli; Yes No p Yes No P
15Dipartimento di Urologia, Policlinico di Milano, Milano;
16Dipartimento di Urologia, Universita Piemonte Orientale,
Operative
Novara, Italy time (m) 338±108 294±111 0.000 379±126 309±109 0.031
Hospital
Introduction: The modified Clavien classification system has stay (day) 16.8±5 12.9±5 0.000 20.4±9.3 14.29±6.2 0.021
been proposed to classify and grade complications in general

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

Discussion and Conclusion: The modified CCS represents 14UrologiaErasmus Medical Center, Rotterdam, The
a practical and easily applicable tool that may help Netherlands;
urologists to classify the complications of radical 15Programma Prostata, Radioterapia Oncologica 1,

cystectomy and urinary diversion in a more objective and Fondazione IRCCS, Istituto Nazionale Dei Tumori, Milano,
detailed way. In our experience, using this CCS tool, radical Italy
cystectomy is associated with a higher morbidity (63%), an
8% reoperation rate and a 1.5% of mortality. Ileal conduit Introduction and Background: Active Surveillance is being
urinary diversion has a higher rate of type I complications. validated worldwide as an alternative to radical treatment
Longer operative time and longer hospital stay are (surgery, radiotherapy and brachytherapy) for low risk prostate
associated with a higher risk of post operative cancer (PC). The aim of the study is to deal with the issue of
complications. overdiagnosis resulting from PSA based opportunistic
screening, limit overtreating potentially indolent PC and avoid
Dindo D, Demartines N and Clavien PA: Classification of therapy-induced side-effects. On these assumptions the SIUrO-
surical complications: a new proposal with evaluation in a PRIAS-ITA project started enrolment in PRIAS (Prostate
cohort of 6336 patiens and result of a survey. Ann Surg 240: Cancer Research International: Active Surveillance), the
205-213, 2004. international study on observational strategy in low risk prostate
Mamoulakis C, Efthimiou I, Kazoulis S et al: The modified cancer patients coordinated by the Erasmus University Medical
Clavien classification system platform for reporting Center in Rotterdam, in December 2009. Patients and Methods:
complications in transurethral resection of prostate. World J Eligibility criteria for SIUrO-PRIAS-ITA: PSA 10 ng/ml,
Urol 29: 205-221, 2011. Gleason Score 6 or Gleason 3+4 in over 69 yr men with <10%
positive cores, T1c or T2, PSA density 0.20, max 2 positive
bioptic cores (<10% positive cores in case of saturation biopsy),
91 biopsy samples according to the volume (8 for 0-40, 10 for 40-
UPDATE OF THE SIURO-PRIAS-ITA 60 and 12 for >60 ml), pathologic review of diagnostic biopsy.
PROJECT, THE ITALIAN EXPERIENCE At inclusion extensive information on the disease,
IN THE PRIAS INTERNATIONAL comorbidities, education, habits are collected and three
COLLABORATIVE STUDY questionnaires administered: IPSS, IIEF and FACTP. Despite
ON ACTIVE SURVEILLANCE the well known problems of misinterpretation of PSA values,
biopsy-induced sequelae and biopsy-resulting false
Tiziana Magnani1, Giario Conti2, Michele Gallucci3, Rocco
negative/positive reports, follow-up is still based on PSA every
Papalia3, Giuseppe Martorana4, Cosimo Bizzari4, Marco
3 months, clinical evaluation every 6 months, evaluation of PSA
Tanello5, Roberto Sanseverino6, Giorgio Napodano6,
doubling time (DT), rebiopsy at 12, 48 and 84 months and
Pierpaolo Graziotti7, Gianluigi Taverna7, Andrea Turci8,
possible extra biopsy (i.e. if PSA DT between 3 and 10 years).
Giacomo Cicchetti8, Enrico Bollito9, Maurizio Colecchia10,
Exit criteria: 3 yr PSA-DT, upsizing and/or upgrading at the
Michelangelo Fiorentino11, Rodolfo Montironi12, Steno
rebiopsy (Gleason 3+4 is accepted in over 69 yr men with
Sentinelli13, Chris Bangma14, Riccardo Valdagni15
<10% positive cores). Results: From December 2009 to March
1Programma Prostata, Fondazione IRCCS, Istituto Nazionale 2012, 255 patients from 8 Italian centers entered the study;
Dei Tumori, Milano; mean age was 65.6 years (min 49 max 80); iPSA was <3 ng/mL
2Urologia, Ospedale Sant’Anna, Como; in 10.6 % patients, between 3 and 6 ng/ml in 54.5%, between 6
3Urologia, Istituto Regina Elena, Roma; and 8 in 27% and >8 in 7.9%. 222 patients are still on protocol
4Urologia, Policlinico Sant’Orsola Malpighi, Bologna; with a median follow-up of 16.6 months (min 2 max 39); 33
5Urologia, Ospedale Civile, Desenzano; discontinued active surveillance based on protocol or personal
6Urologia, Ospedale Umberto I, Nocera Inferiore; decision. Reasons for discontinuation were upgrading at
7Urologia Istituto Clinico Humanitas, Rozzano; rebiopsy in 4 cases, upsizing in 9 and upgrading plus upsizing
8Urologia Ospedale M. Bufalini, Cesena; in 5, PSA DT <3 years in 2 cases, other causes in 2 cases (a
9Anatomia Patologica, Ospedale San Luigi Gonzaga, patient on follow-up for bladder cancer in a center not
Orbassano; participating in SIUrO-PRIAS-ITA was erroneously prescribed
10Anatomia Patologica, Fondazione IRCCS Istituto hormonal therapy; a patient could not stop anticoagulants and
Nazionale Dei Tumori, Milano; repeat biopsy), personal choice in 11 patients. Discussion and
11Anatomia Patologica, Policlinico Sant’Orsola Malpighi, Conclusion: Active Surveillance is proving an acceptable
Bologna; alternative for patients with low risk PC, which might harbour
12Anatomia Patologica Ospedali Riuniti, Torrette Di Ancona; an indolent PC and thus overtreatment and treatment induced
13Anatomia Patologica Istituto Regina Elena, Roma, Italy; toxicities can be avoided. Unfortunately, the definition of

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

indolent cancer is still cloudy and there is no test yet able to body) and a MRI abdominal-pelvic were done and were
distinguish between aggressiveness PC, which needs immediate negative. June 2011: after a proper psychotherapeutic
treatment, and low aggressive PC. For this reason Active counseling, the patient has undergone a new operation. The
Surveillance should be carried on within protocols with well intraoperatory histological examination of corpora cavernosa,
defined criteria for inclusion, follow-up management and of peri-urethral tissue and of neurovascular bundle, confirmed
discontinuation. The very important follow-up phase should be neoplastic involvement. The cavernosal bodies, the glans, the
organized according to a precise scheme to guarantee high neurovascular bundle and great part of anterior urethra were
standard of care and switch to therapy should any modification excised. A portion of proximal urethra was preserved and
in the clinical situation occur. Every effort should be made to covered with penile skin. Conclusion: In literature, only 13
systematically check adherence to the protocol criteria and limit cases of epithelioid sarcoma of the penis have been reported,
the number of patients lost at follow-up. so far. The low incidence, the slow progression of the disease
and the aspecific ultrasound aspect, can justify a late diagnosis.
In young patients suffering for idiopathic acquired penile
93 curvature, greatest attention must be placed, with possible
EPITHELIOID SARCOMA OF THE PENIS: proposal of immediate biopsy or of explorative surgical
A CASE REPORT intervention.
Giovanni Passaretti1, Marco Borghesi1, Valerio Vagnoni1,
Alessandro Franceschelli2, Cristian Vincenzo Pultrone1,
94
Giovanni Christian Rocca1, Giorgio Gentile2,
THE IMPACT OF THE EXTENT OF LYMPH-NODE
Fulvio Colombo2
DISSECTION DURING RADICAL CYSTECTOMY
1Clinica Urologica, Azienda Ospedaliera Universitaria FOR BLADDER CANCER ON CANCER-SPECIFIC
Policlinico S. Orsola Malpighi; SURVIVAL
2Andrologia Colombo, Azienda Ospedaliera, Universitaria
Marco Borghesi, Riccardo Schiavina, Fabio Manferrari,
Policlinico S. Orsola Malpighi, Bologna, Italy
Eugenio Brunocilla, Barbara Barbieri, Giovanni Passaretti,
Valerio Vagnoni, Manola Marini, Francesco Mengoni,
Introduction: We reported a case of epithelioid sarcoma of the
Giuseppe Martorana
penis initially diagnosed and treated as Peyronie’s disease.
Patients and Methods: May 2010: a 20 years old man came to Clinica Urologica Azienda Ospedaliera Universitaria
our outpatient department, referring the onset of a progressive Policlinico S. Orsola Malpighi, Bologna, Italy
left dorsal penile curvature (about 90˚) that started 3 years
earlier. The patient was evaluated with 2 US examinations that Background: We evaluated the associations between the
revealed two sites of tunical thickening with normal number of lymph nodes retrieved during radical cystectomy
hemodynamic evaluation. The physical examination (RC) for bladder cancer (BC) and the cancer-specific survival
demonstrated a dorsal fibrotic plaque of about 2.5 cm. A new (CSS). Patients and Methods: We evaluated 229 consecutive
US confirmed presence of a fibrotic plaque determining a patients submitted to RC for BC between November 1995
dorsal left deviation (39×25×5 millimetres) that prevented and October 2009 with complete follow-up data. Exclusion
sexual intercourse. Results: A juvenile form of Peyronie’s criteria were 1) neoadjuvant or adjuvant therapy 2) palliative
Disease was diagnosed and the patient was scheduled for RC 3) pNx patients 4) incomplete clinical and pathological
surgical treatment (plaque’s incision/excision and grafting). The data. Therefore, we evaluated 167 patients. Patients were
surgical approach resulted difficult with penile degloving divided into two LN-groups according to the number of LNs
hampered by tenacious adherence between superficial layers retrieved: group 1 (n=56, 33%) had 1 to 12 LNs removed;
and albuginea; the great part of the left corpus cavernosum group 2 (n=111, 67%) had 13 or more LNs removed. Primary
appeared substituted by a very tough tissue which deeply endpoint was the evaluation of CSS. Results: The mean
involved the erectile tissue. The intraoperative biopsy was follow-up was 52.6 months (1-172). Overall, among the 167
consistent with the possible diagnosis of mesenchymal patients, the CSS rate was 67.1% and 57.7% at 5-ys and 10-
epithelioid cancer with sarcomatoid differentiation. Because of ys respectively. Cancer-specific death was observed in 51
lack of informed consent for radical excision and in order to (30.5%) patients. The mean number of LNs obtained was
wait for the definitive report from the pathologist, we proceed 16.5 (143); 23 (10%) patients were N+, with a mean number
with the original plane, performing a wide excision of the of positive LN was 5.6 (1-19). Figure 1 shows the Kaplan-
pathological tissue and using buccal mucosa and acellular Meier curve for CSS with patients stratified by LN-group. At
porcine dermal matrix for grafting. The final histological report univariate and multivariate Cox analysis for clinical and
confirmed the diagnosis of epitheliod sarcoma; a CT scan (total pathological characteristics correlated with CSS, patients with

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

lower pathological stage, negative LN, conventional 97

transitional cell carcinoma (TCC) and more LN retrieved had FEASIBILITY, SAFETY AND 1 YEAR
better CSS. Conclusion: In our study, patients undergoing a FOLLOW UP OF EN BLOC TRANSURETHRAL
more extensive pelvic lymphnode dissection (PLND) have a RESECTION OF BLADDER TUMOR COMPARED
better CSS than those undergoing a more limited [Link] TO A MATCHED COHORT OF PATIENTS
data support a possible role of PLND on cancer outcome. SUBMITTED TO STANDARD TUR
Although the extent of PLND may indirectly influence the
Carlo Introini, Angelo Naselli, Paolo Puppo,
BCR because of the Will Rogers phenomenon, the inclusion
Francesco Germinale
of both node-positive and node-negative patients may
partially exclude this bias. Urologia Istituto Tumori, Genova, Italy

Background: The main limit of the standard TUR of bladder

96 cancer is the fragmentation of the specimen which may hamper
IMPACT OF RADICAL PROSTATECTOMY IN HIGH accuracy of pathological examination and oncological results.
RISK PROSTATE CANCER PATIENTS The en bloc TUR overcomes the problem. Unfortunately only
small lesions fit for the procedure as the specimen is retrieved
Carlo Introini, Angelo Naselli, Paolo Puppo
through the resectoscope with a standard evacuator. We
Urologia, Istituto Tumori, Genova, Italy developed a simple technical modification to retrieve specimens
up to 4.5 cm and compared results in a matched cohort of
Introduction and Objectives: High risk prostate cancer is an patients submitted to standard TUR. Objective: To assess
aggressive disease with an impaired long term survival feasibility, safety and 1 year recurrence rate of the technique of
prospective. We reviewed our institutional prospective modified en bloc TUR (EBTUR). Design, Setting, Participants:
database to assess the impact of radical prostatectomy and of From March to September 2010, 26 consecutive patients gave
adjuvant/salvage treatments. Patients and Methods: The their consent and were scheduled for EBTUR of a bladder
review of a prospective database of 1179 subjects submitted tumor, 1 patient harboring invasive cancer was excluded from
to radical prostatectomy from 1991 to 2011 for clinically the analysis. Data were matched with a cohort of 50 patients
localized prostate cancer disclosed that 788 individuals had a submitted to standard TUR enrolled in a prospective trial with
complete dataset and 433 had one or more of the subsequent similar clinical and pathological characteristics. Results: There
characteristics: preoperative PSA >= 20 ng/mL, pathological was no significant difference in regard to age, male to female
stage T3/N0, pathological primary Gleason score of 4 or 5. ratio, ASA score, proportion of primary/recurrent cases, of
Excluding 28 subjects who received immediate hormonal single/multiple lesions, Ta/T1 lesions, lesions >3 or <3 cm in
therapy, 405 patients remained for the analysis. 401 had a the 2 groups. The median dimension of the lesion extracted
minimum follow-up of 3 months, range 3±188, median 36. intact from the bladder in the EBTUR group was 2 cm, range
132 (33%) had positive surgical margins Results: From 0.5-4.5 cm. 11 lesions were equal to or greater than 3 cm, and
March 2007, interquartile range March 2005 - July 2008, 31 none of them was solid. Median postoperative catheter removal
(8%) were submitted to adjuvant radiotherapy. 43 (11%) were and discharge time was 2 days in both groups. No death or
submitted to salvage radiotherapy at a median time of 31 major surgical or medical complications occurred. Overall grade
months (range 7-106), whereas 51 (13%) to salvage hormonal I-II, according to the Clavien Dindo classification,
therapy at a median time of 29 months (range 4±103). 11 complications rate was 6/26 (28%) compared to 8/50 (16%) of
(2.7%) patients died at a median follow-up of 45 months, the corresponding cohort (p=0.657). All patients completed 1
range 19±147 months, 4 of prostate cancer and 7 of unrelated year of follow-up.1 year recurrence rate was 11/26 (42%) in the
causes. A subgroup of 276 (69%) patients who were not EBTUR group and 24/50 (48%) in the standard group
submitted to any adjuvant or salvage therapy had a PSA <0.4 (p=0.818). The main limits of the analysis were 1) the
ng/mL at a median follow-up of 31 months, range 3±149 prospective non randomized dataset; 2) the small number of
months. 262 (95%) were completely continent. 34 out of 123 patients enrolled. Conclusion: Feasibility, safety and 1 year
(27%) evaluable had a satisfactory sexual activity with or recurrence rate of EBTUR is comparable to a matched cohort of
without the use of oral drugs. Conclusion: High risk prostate patients submitted to standard TUR. The objective advantage of
cancer treated by radical prostatectomy offered excellent long an accurate pathological examination (identification of micro
term survival in our series even if the use of radio or focal invasion of lamina propria or of muscular wall, surgical
hormonal therapy was limited to a minority of cases. Notably margins assessment) is associated with a substantial safe
“cured” patients preserve almost always their urinary technique. Long term data and larger dataset of cases are
continence while sexual activity is impaired mainly due to the necessary to demonstrate an advantage in terms of recurrence
aggressive surgery performed. or progression.

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

98 BAND IMAGING MODALITY ON NON MUSCLE

MALIGNANT MESOTHELIOMA OF THE INVASIVE BLADDER CANCER RECURRENCE
TUNICA VAGINALIS OF THE TESTIS
Carlo Introini, Carlo Introini, Angelo Naselli, Luca Timossi,
Marco Borghesi1, Giovanni Passaretti1, Paolo Puppo, Francesco Germinale
Alessandro Franceschelli2, Giorgio Gentile2,
Urologia Istituto Tumori, Genova, Italy
Fulvio Colombo2
1Clinica Urologic,a Azienda Ospedaliera Universitaria Background: Narrow band imaging (NBI) is an optical
Policlinico S. Orsola Malpighi; enhancement technology for endoscopy which consists of
2Andrologia, Colombo Azienda Ospedaliera, Universitaria filtering the standard white light into 2 bandwidths of
Policlinico S. Orsola Malpighi, Bologna, Italy illumination centered on 415 nm (blue) and 540 nm (green).
NBI cystocopy increases the bladder cancer detection rate and
Purpose: Mesothelioma is a malignant tumor arising from therefore it may influence favorably recurrence rate. Objective:
pleura, peritoneum and pericardium; less than 5% originate To assess impact of TUR performed in NBI modality on non
from the tunica vaginalis of the testis. We report the case of muscle invasive bladder cancer with 1 year recurrence rate.
a 67 years old patient who noticed a progressive volumetric Design, Setting, Participants: Consecutive patients with overt
increase of the right scrotum since 2009. In 2009 Ultrasound or suspected bladder cancer were included in a prospective
(US) showed a diffuse thickening both of the albuginea and study designed to disclose a 10% absolute difference of 1 year
vaginalis of the right testicle associated to voluminous recurrence rate in favor of cases submitted to NBI TUR.
hydrocele. MRI confirmed a right hydrocele associated with Excluding patients with muscle invasive bladder cancer,
contrast-enhanced excretions and diffuse thickening of the negative pathological examination or without follow-up, the
tunica vaginalis. The appearance was diagnosed as a study population included 148 subjects randomized from
widespread vaginalitis and the patient was followed-up. In August 2009 to September 2010 to NBI TUR, 76 cases, or
May 2011 the patient presented to our outpatient department standard TUR, 72 cases. Clinical, pathological characteristics
because of a painful right-sided scrotal swelling; the physical and incidence of intravesical instillations in the 2 groups were
examination demonstrated a voluminous hydrocele of hard similar. Results: Overall 25 patients (32%) recurred in the NBI
consistency that extended in inguinal region. The group and 37 (51%) in the standard group (Chi square test,
radiological assessments confirmed the thickening and p=0.034). In multivariate analysis NBI was a protective factor
contrast-enhancement both of the albuginea and the tunica against recurrence (odds ratio 0.4472, p=0.0297) as well
vaginalis. Patient underwent surgical exploration: the tunica adjuvant topic therapy (odds ratio 0.378, p=0.0309).
vaginalis appeared to include by numerous small nodular Conclusion: TUR performed in NBI modality was able to
masses which extended to the albuginea. Intraoperative reduce significantly and independently the 1 year recurrence
biopsy showed a malignant mesenchymal lesion, probably a rate of non muscle invasive bladder cancer of at least 10% in
mesothelioma. So we decided to perform a right radical terms of absolute difference. Trial Registration: NCT0100421.
orchiectomy. The final histological examination confirmed
the diagnosis of malignant epithelioid mesothelioma of the
tunica vaginalis, with sarcomatoid and rhabdoid 100
differentiation. A post-operative CT showed pulmonary, INSULIN RESISTANCE (IR) AND PROSTATE
hepatic, pancreatic and bone multiple metastases. CANCER (PCa):THE EFFECT OF NEOADJUVANT
Conclusion: Malignant mesothelioma of the tunica vaginalis ANDROGEN DEPRIVATION THERAPY ON IR IN
is an unfrequent and, in general, slow-growing neoplasia; PATIENTS WITH A DIAGNOSIS OF PCa
even if prognosis for these mesotheliomas appear to be better
Renato De Domenico1, Giuseppe Quarto2,
than intrathoracic or intraabdominal disease, with a better
Domenico Sorrentino2, Matteo Ferro3, Vincenzo Altieri4,
survival and the clinical and radiological pattern is very
Antonio Di Girolamo3, Daniela Terracciano5,
similar to that of hydrocele, in doubtful cases fine needle
Rosario Pivonello6, Annamaria Colao6,
aspiration cytology, biopsy and/or surgical exploration
Mariano Galdiero6, Pasquale Vitale6,
should not be postponed because sometimes the disease can
Federica Cariati6, Modestino Tronino3, Sisto Perdonà2
have a highly aggressive course
1UOC-Urologia, Istituto Nazionale Tumori Fondazione “G.
Pascale”-Napoli;
99 2Urologia, Istituto Nazionale Tumori IRCCS “Fondazione G.

A RANDOMIZED PROSPECTIVE TRIAL TO ASSESS Pascale”, Napoli;

IMPACT OF TUR PERFORMED IN NARROW 3Urologia, Università Federico II, Napoli;

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

4Urologia,Università Degli Studi Di Salerno; the relationship between insulin resistance and
5Patologia,
Clinica Università Federico II, Napoli; pathophysiology and prognosis of PCa.
6Endocrinologia Università Federico II, Napoli, Italy

1 Horwich A, Parker C and Kataja V: On behalf of the ESMO

Background: PCa represents the most prevalent neoplasm, Guidelines Working Group*; Prostate cancer: ESMO Clinical
with an incidence rate of around 80 cases per 100000 per year, Recommendations for diagnosis, treatment and follow-up;
and the most common cause of cancer death in men (1). PCa Annals of Oncology 20(Suppl 4): iv76-iv78, 2009.
has a multifactorial etiology and, in recent years, insulin and 2 Shastri BR and Yaturu S: Metabolic Complications and
insulin like growth factor have been suggested to play a role in Increased Cardiovascular Risks as a Result of Androgen
its development, although the mechanism underlying this Deprivation Therapy in Men with Prostate Cancer; Prostate
effect has not yet been completely clarified (2). Androgen Cancer 2011, Article ID 391576, 9 pages
Deprivation Therapy (ADT) is nowadays one of the main tools doi:10.1155/2011/391576.
in the medical treatment of PCa. ADT has been found to be 3 Collins L and Basaria S: Adverse effects of androgen
associated with insulin-resistance (IR) and a consequent deprivation therapy in men with prostate cancer: a focus on
impairment of metabolic homeostasis (3). The aim of the metabolic and cardiovascular complications;.Asian J Androl.
present study was to evaluate the role of ADT in the 2012 Feb 20. doi: 10.1038/aja.2011.109.
development of IR and the correlation between IR index and
the markers of PCa. Patients and Methods: Nineteen patients
with PCa (age 58-74, mean: 66.2±4.1 yrs) were enrolled in the 101
study and randomly divided into two groups: 9 patients were IS THERE A DIFFERENCE IN QUALITY
treated with ADT (cyproterone acetate, 400 mg/die) for three OF LIFE BETWEEN INTRAVESICAL
months whereas 10 patients remained untreated for the same CHEMOTHERAPY AND BCG? RESULTS
period before surgical intervention. None of them had OF A RANDOMIZED PHASE II TRIAL
diabetes, three were obese, while five had metabolic syndrome
Paolo Gontero1, Marco Oderda1, Alberto Gurioli1,
according to ATP III classification. The study was performed
Francesco Marson1, Anja Mehnert2, Micheal Rink2,
at baseline and after three months of ADT or no treatment.
Marianne Schmid2, Luis Kluth2, Giovanni Pappagallo3,
The evaluation of anthropometric parameters (weight, BMI,
Filippo Sogni4, Francesco Sanguedolce5,
waist, hip, waist-hip ratio (WHR)) and insulin-resistance
Giuseppe Martorana5, Felix Chun3
indexes, as well as metabolic and hormonal parameters was
performed in all patients at baseline and after 3 months, while 1Department of Urology of Turin, Department of Urology-1,
at diagnosis biochemical and histological PCa markers (total A.O.U. San Giovanni Battista, Turin, Italy;
prostate specific antigen (PSA), free (f) PSA, free on total 2Institut und Poliklinik für Medizinische Psychologie

PSA ratio (f/t), prostate health index (PHI), PCA 3, Gleason Zentrum fur Psychosoziale Medizin University of Hamburg,
score) were also evaluated in all patients. Results WHR at Institut und Poliklinik für Medizinische Psychologie
diagnosis was directly correlated with PCA 3 and fPSA Zentrum für Psychosoziale Medizin, Hamburg, Germany;
(p=0.035 and p=0.034 respectively); no other correlations 3Oncology Unit Noale Hospital, Noale;

were found between IR indexes or metabolic parameters and 4Department of Urology, University of Eastern Piedmont,

biochemical or histological PCa markers. In patients treated Maggiore della Carità Hospital, Department Of Urology,
with ADT, HOMA-1 (p=0.01), HOMA-2 (p=0.01), Quicky Novara;
(p=0.01), McAuley (p=0.01), fasting insulin (p=0.01) and 5Department of Urology, University of Bologna, Bologna,

post-glucose load insulin AUC (p=0.01) were significantly Italy

increased while testosterone and 17 β-oestradiol were
significantly decreased (p=0.008 and p=0.01) after 3-months Objectives: According to current evidence, BCG is perceived
of therapy. Conversely, no significant change was found in as less torelable than intravescial chemotherapy. Both these
anthropometric, metabolic and hormonal parameters as well treatment options can be used as adjuvant treatment in
as in insulin-resistance indexes in the subgroup of patient not intermediate-risk NMIBC. This is the first study to
treated with ADT. Conclusion: The preliminary results of the prospectively evaluate and compare the quality of life (QoL)
present study demonstrate that WHR, but not insulin of intermediate-risk NMIBC patients treated with
sensitivity, is correlated with biochemical markers of PCa. chemotherapy or BCG. Gemcitabine, a promising intravesical
Furthermore, ADT, represented by cyproterone acetate for agent for its efficacy and tolerability, was employed in the
three months, is able to impair insulin sensitivity according to chemotherapy arm. Patients and Methods: We enrolled 120
the change in IR indexes. Further evaluations on a large cohort intermediate-risk NMIBC patients. 61 were randomized to
of patients are mandatory to draw a definitive conclusion on receive GEM 2000 mg/50 cc weekly for 6 weeks

1908
 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

(maintenance monthly for one year), while 59 BCG ASAP using the Kaplan-Meier survival curves. Results:
Connaught 1/3 dose weekly for 6 weeks (maintenance 3 Among the 101 patients with ASAP, the PCa detection rate at
weekly instillations at 3, 6 and 12 months). QoL was rebiopsy was 36.6%, being 27.7% at the first rebiopsy (101
measured by EORTC QLQ-C30 and BLS-24 questionnaires at cases) and 37.5% at the second rebiopsy (N 24). Mean time
the following time intervals (T0 baseline, T1 after completion from ASAP diagnosis to first rebiopsy was 11.8 months,
of induction cycle, T2 after 1 year). Adverse events were whereas mean time from first to second rebiopsy was 17.5
graded according to the CTCAE version 3.0. Results: 88 months. According to Kaplan-Meier survival curves, mean
patients completed the study (47 in BCG-arm and 41 in the PCa-free survival in ASAP patients was 45.4 months (standard
GEM-arm). Mean age was 67.4 years. At T1, the GEM-group error 5.69) (Figure 1). Conclusion: our 36.6% PCa detection
showed a significant better QoL in cognitive (p=0.01) and rate at rebiopsy after diagnosis of ASAP, comparable to data
emotional (p 0.03) functioning with moderate effect sizes as reported in the literature, warrants the repetition of prostate
well as better QoL in urinary symptom distress (p=0.03) and biopsy. However, the long time elapsed before development of
intravesical treatment problems (p=0.01). At T2, the GEM- PCa questions the necessity of an early rebiopsy, suggesting
group showed a significant better QoL in cognitive functioning the safe adoption of a longer time interval before repeating this
(p=0.01) with a moderate effect size as well as less symptom procedure.
distress regarding nausea and vomiting (p=0.001) with a large
effect size. No significant differences were recorded in the
Global Health Status. Multivariate analyses showed no
significant differences between the BCG and GEM group in
all QoL dimensions (EORTC-QLQ-C30) including bladder
cancer-specific quality of life. Treatment was well-tolerated in
both groups, with a higher incidence of adverse events in the
BCG-arm. Conclusion: Intravesical instillations caused a
worsening of patients’ QoL, irrespectively of the drug used.
Gemcitabine showed a significant better tolerability profile
than BCG in few specific items on univariate analysis not
clearly attributable to intravesical therapy. Notably these
differences were lost on multivariate analysis.

103
ATYPICAL SMALL ACINAR PROLIFERATION
(ASAP): IS REPEAT BIOPSY STILL WARRANTED?
Marco Oderda, Francesca Peraldo, Francesco Soria,
Simone Giona, Andrea Zitella, Paolo Gontero
Department of Urology-1, University of Turin, A.O.U. San
Giovanni Battista, Turin, Italy

Introduction: Atypical small acinar proliferation (ASAP)

indicates a situation of diagnostic uncertainty, highly 104
predictive for prostate cancer (PCa) on subsequent biopsies. TREATMENT OUTCOME OF PATIENTS WITH
The PCa detection rate is estimated around 34-60% after an METASTATIC RENAL CELL CARCINOMA WITH
initial diagnosis of ASAP. According to recent evidence, the POOR HISTOLOGICAL FEATURES
presence of ASAP would warrant a repeat biopsy within 3-6
Riccardo Ricotta1, Maria Olga Giganti2, Sara Di Bella2,
months. Aim of the current study is to evaluate the natural
Lisa Pietrogiovanna2, Elena Strada3, Antonio Galfano3,
history of ASAP and discuss indications and timing for a
Manuela Bramerio4, Aldo Massimo Bocciardi3,
repeat biopsy. Patients and Methods: We analyzed our
Marcello Gambacorta4, Salvatore Siena2
database of transperineal prostate biopsies performed in the
period 2002-2010. We enrolled in study 101 patients who 1Oncologia Ospedale Niguarda Ca’ Granda, Milano;
underwent repeat biopsy at any time after a previous diagnosis 2Clinica di Oncologia Medica Niguarda, Milano;
of ASAP. We analyzed the PCa detection rate at the rebiopsy 3Cattedra di Urologia Niguarda, Milano;

and we estimated the PCa-free survival after diagnosis of 4Anatomia e Citoistologia Patologica Niguarda, Milano, Italy

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

Background: Sarcomatoid dedifferentiation in metastatic In our series pts with poor differentiated mRCC had an
renal cell carcinoma (mRCC) is well established to be unfavorable prognosis, independently of the presence of
associated with biological and clinical aggressiveness that sarcomatoid component. The response to first-line therapy
negatively impacts response to therapy. We assessed the influenced disease outcome, in terms of greater PFS,
influence of poor histological differentiation on clinical conversely subsequent treatments had a marginal impact on
outcome of treated patients (pts). Patients and Methods: A clinical course. Due to the absence of definitive data, further
single center database was reviewed to identify pts with studies to characterize tumor biology and develop novel
mRCC with the following histological features of poor treatment strategies are needed.
outcome to medical therapy. Pts included in the present
study had sarcomatoid or poor differentiated (grade 3 or 4
according to the Fuhrman classification) mRCC histologies. 105
Clinical outcome was evaluated as objective responses and PHASE II STUDY OF PACLITAXEL IN PATIENTS
progression-free survival (PFS), determined on the basis of WITH METASTATIC PENILE CANCER
the first-line treatment. Results: Twenty pts [14 M, 6 F;
Matteo Ferro1, Gianmarco Silvestre2, Umberto Greco2,
median age 62.6 years (range, 47-80 years); ECOG
Anna Rega2, Gaetano Savoia2, Giuseppe Quarto3,
performance status (PS) of 0-1 in 15 pts and PS of 2 in 5
Domenico Sorrentino3, Renato De Domenico3,
pts] were included in this analysis. Fourteen pts (70%) had
Sisto Perdonà3, Florestano Montanino4, Carlo Buonerba5,
a metastatic disease at the time of initial diagnosis and 19
Piera Federico5, Pasquale Rescigno5, Giuseppe Di Lorenzo5,
pts underwent nephrectomy prior to medical therapy. Tissue
Vincenzo Altieri6
samples for histological characterization were obtained from
primitive tumor in these 19 pts. In one case pathological 1Urologia Università degli Studi Federico II, Napoli;
examination was done on the lung metastasis. Histology 2Urologia A.O.U., Ruggi D’Aragona-Salerno;
subtypes of the study population included 13 clear cell, 1 3Urologia, Istituto Nazionale Tumori IRCCS “Fondazione G.

collecting duct and 6 high grade unclassified carcinoma. A Pascale”, Napoli;

sarcomatoid component was found in 9 cases. According to 4Urologia, Università Federico II, Napoli;

MSKCC prognostic score, risk group distribution was 15% 5Oncologia Medica, Università Federico II, Napoli;

good risk (n=3), 45% intermediate risk (n=9), and 40% poor 6Urologia, Università degli Studi di Salerno, Salerno, Italy

risk (n=8). All pts began medical treatment during the

period of January 2008 to October 2011 at Ospedale Background: Previously published preliminary findings
Niguarda Ca’ Granda, Milan. First-line therapy was showed promising activity of paclitaxel in chemotherapy-
sunitinib in 12 pts (60%), temsirolimus in 3 pts (15%), pretreated metastatic penile [Link] aim was to evaluate
sorafenib in 2 pts (10%) and bevacizumab plus interferon- the activity and safety of paclitaxel in pretreated metastatic
alpha in 2 pts (10%). One patient was treated with penile cancer. Patients and Methods: Twenty-five patients
chemotherapy containing adriamycin and ifosfamide. were enrolled in a single-arm phase 2 multicentre study and
Among 19 pts evaluable for response, progressive disease treated with 175 mg/m2 paclitaxel at 3-wk intervals until
(PD) was shown in 11 pts (57.9%) partial responses (PR) disease progression or irreversible toxicity. The objective
were observed in 4 pts (20%), while 4 pts (20%) had stable response rate was the primary end point. Safety,
disease (SD) as their best response. In overall study progression-free survival (PFS), and overall survival (OS)
population median PFS was 15.1 weeks [(95% Confidence were secondary end points. Results: Partial responses were
Interval (CI)=9.3-21)]. No difference in PFS was observed observed in 20% (5 of 25 patients). Grade 1-2 neutropenia,
on the basis of the presence or absence of sarcomatoid nausea, and oral mucositis were the most common side-
dedifferentiation [12.8 weeks (95% CI=8.4-17.2) vs. 16.8 effects, noted in 13, 9, and 8 patients, respectively. Grade 3-
weeks (95% CI=11-22.6), respectively. Log-rank test: 4 neutropenia was reported in seven patients (28%). Median
p=0.97]. Instead the 8 pts with disease control rate (PR + PFS was 11 wk (95% confidence interval [CI], 7-30);
SD) as best response had a significant greater PFS when median OS was 23 wk (95% CI, 13-48). Median survival in
compared with pts with PD [26.3 weeks (95% CI=12.3- responders was 32 wk (95% CI, 20-48), (Figures 1 and 2).
40.3) vs. 12.4 weeks (95% CI = 8.3-16.5), respectively. Log- One limitation of our study was the limited accrual, which
rank test: p=0.004]. Among the 19 pts with documented PD, did not reach the target of 27 patients, due to the typical
only 8 pts (42%) received second-line treatment, due to the slow enrolment of a rare disease. Conclusion: Final results
rapid clinical worsening. However none of these 8 pts had of this study demonstrate that paclitaxel is moderately active
radiological response or any degree of tumor shrinkage. and well tolerated. Further trials, which may also explore
Median overall survival has not been reached and the 6- the combination of paclitaxel with other agents, are required
months survival rate was 70%. Discussion and Conclusion: to confirm our findings.

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

UO Radioterapia Oncologica AOU, Policlinico di Modena,

Italy

Aim: Curative treatment of patients with prostate cancer

comprises surgery, radiotherapy (RT) with or without
hormonotherapy. In external beam RT dose escalation is
currently investigated to improve outcomes and several studies
provide strong evidence for a dose-response relation of local
tumor control, biochemical progression free survival and
progression free survival. It’s commonly known that dose
escalation can also be achieved by increasing the dose per
fraction above 2 Gy (as in our study) and several studies
Figure 1 showed that prostate cancer cells may be strongly susceptible
to this regimen due to their low alfa/beta ratio. Dose escalation
and hypofractionation may hypothetically increase acute and
late genitourinary and gastrointestinal toxicity but the
introduction in recent years of IMRT may allow us to deliver
higher doses without increasing toxicity. Patients and
Methods: From February 2008 to December 2011 a total of
64 patients with histologically proven prostate cancer
underwent radical radiotherapy treatment using
hypofractionated regimen with or without concomitant
hormonotherapy; all of them were treated using image guided
radiotherapy with Tomotherapy. Median age was 71years
(range 57-79 years). Eight of 64 patients had low risk prostate
cancer (12.5%), 4 intermediate risk (6.5%) and 52 high risk
(81%). All patients underwent rectal ultrasonography, biopsy,
Figure 2 abdominal CT scan and pelvis RMN; at the end of the staging
protocol 13 patients (20%) had T1 prostate cancer, 7 T2, 10
1 Bermejo C, Busby E, Spiess PE et al: Neoadjuvant pts had T3a (15.6%) and 34 pts (53.1%) had T3b; abdominal
chemotherapy followed by aggressive surgical consolidation lynphoadenopathy were found in only 5 pts (N1 stage). Of all
for metastatic penile squamous cell carcinoma. J Urol 177: patients, 34 received neoadjuvant (53.1%) and/or concomitant
1335-1338, 2007. hormonotherapy, while 30 pts (46.8%) received even adjuvant
2 Pizzocaro G, Nicolai N and Milani A: Taxanes in hormonotherapy. Analysis of biopsies revealed a Gleason
combination with cisplatin and fluorouracil for advanced Score less than 7 in 23 pts, equal to 7 in 15 pts and superior in
penile cancer: preliminary results. Eur Urol 55: 546-551, the other 16 patients; median Gleason score was 7.
2009. Radiotherapy was delivered to a median dose of 70 Gy (range:
3 Di Lorenzo G, Cartenı’ G, Autorino R et al: Activity of 45-74 Gy). Clinical target volume included just prostate in 2
paclitaxel in pretreated metastatic penile cancer patients. pts, prostate and seminal vescicles in 34 patients (53%), while
Anticancer Drugs 20: 277-280, 2009. only in 28 patients (43.7%) pelvic abdominal radiotherapy
(with prophilactic intent) was performed due to high risk of
lymphatic extension (based on Roach algorithm). Results:
106 After a median follow-up of 20 months 57 out of 64 patients
DOSE-ESCALATED RADIOTHERAPY are still free from disease (90%), while 5 pts (8%) are alive
TREATMENT USING TOMOTHERAPY IN A with locoregional disease and 2 pts (2%) developed metastatic
MODERATELY HYPOFRACTIONATED disease. All patients with locoregional or systemic disease
REGIMEN FOR PROSTATE CANCER: were submitted to hormonotherapy with LHRH. Radiotherapy
RETROSPECTIVE MONOINSTITUTIONAL treatment was well tolerated with only 4 patients complaining
EXPERIENCE AT THE RADIOTHERAPY acute severe urinary toxicity, while 1 pt developed Grade 3
UNIT OF AOU POLICLINICO DI MODENA acute rectal side-effect. Late Grade 3 rectal toxicity was
reported in 4 patients while Grade 2 urinary toxicity in 3 pts;
Alessio Bruni, Ercole Mazzeo, Bruno Meduri, Enrico Turco,
no grade 3 urinary late toxicity were found. No treatment
Biancaluisa Lanfranchi, Laura Rubino, Filippo Bertoni
related deaths were encountered in our population.

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

Conclusion: Hypofractionated dose escalated radiation 17Dipartimento di Urologia, Ospedale Padre Pio Da
treatment using IG-IMRT with Tomotherapy seems to be Pietrelcina, Vasto;
feasible and well tolerated being able to obtain optimal 18Dipartimento di Urologia, Policlinico Di Milano, Milano;

outcomes reducing total treatment time without increasing 19Dipartimento di Urologia, Clinica Urologica, University Of

acute and severe side-effects. Hypofractionation and dose Brescia, Brescia;

escalation in radical or concomitant (hormonotherapy) setting 20Dipartimento di Urologia, Università Piemonte Orientale,

should be considered in the management of non surgical Novara;

prostate cancer. 21Dipartimento di Urologia, Presidio Ospedaliero Le

Molinette, Torino, Italy

107 Introduction: The modified Clavien classification system

EVALUATION OF TRANSURETHRAL BLADDER (CCS) has been proposed to classify and grade complications
RESECTION COMPLICATIONS: A MODIFIED in general surgery. It is increasingly becoming popular in
CLAVIEN CLASSIFICATION SYSTEM ANALYSIS urology although has never been used to date in common
procedures such as transurethral resection of bladder tumor
Cosimo De Nunzio1, C. Leonardo2, L. Cindolo3,
(TURB). The aim of our study is to evaluate the applicability
A. Antonelli4, F. Cancrini5, A. Cantiani5, C. Ceruti6,
of the modified CCS in reporting and grading the severity of
C. De Dominicis2, F. De Luca7, P. Destefanis6, V. Di Santo8,
perioperative complications in patients with bladder tumor
F. Esperto5, M. Falsaperla9, H. Fattahi5, M. Gallucci10,
treated with TURB. Patients and Methods: A consecutive
E.r. Gonzales11, R. Lombardo5, M.a. Maestro11, G. Maugeri9,
series of patients with bladder lesions who underwent
A. Minervini12, V. Pagliarulo13, P. Parma7, S. Perdonà14,
transurethral resection of bladder tumour (TURB) from April
A. Porreca15, R. Rocco16, L. Schips17, S. Serni12,
2011 to August 2011 at six academic centres were evaluated
M. Serrago18, C. Simeone19, G. Simone10,
for complications occurring up to the end of the first
R. Spadavecchia13, C. Terrone20, A. Tizzani21, A. Tubaro5
postoperative month. Variables analyzed for each patient were:
1Urologia, Azienda Ospedaliera Sant’Andrea, Grottarossa, age, sex, diabetes, hypertension, ischemic heart disease, score,
Roma; tumor size, number of lesions, grade of tumor, anticoagulation
2Dipartimento di Urologia, Università “ La Sapienza”, therapy, type of diversion, operation time, preoperative
Policlinico Umberto I˚, Roma; hydronefrosis and BMI. All complications were prospectively
3Dipartimento di Urologia, Ospedale Padre Pio Da recorded and classified according to the modified CCS.
Pietrelcina, Vasto; Results were presented as complication rates per grade. Chi-
4Dipartimento di Urologia, Clinica Urologica, University of square, Kruskal Wallis tests and logistic regression analysis
Brescia, Brescia; were used for statistical analysis. Results: 275 patients were
5Dipartimento di Urologia, Università “La Sapienza”, consecutively enrolled. Mean age was 68.26±8.1 years; mean
Ospedale Sant’Andrea, Roma; BMI was 28.3±4 Kg/m2, mean tumour size was 2.38±2.3 cm;
6Dipartimento di Urologia, Presidio Ospedaliero Le mean number of tumour lesions was 2.52±2.3. All patients
Molinette,Torino; underwent a monopolar TURB. Mean operative time was
7Dipartimento di Urologia, Ospedale Fatebenefratelli ed 43±28 m. Fifty-six complications were recorded in 51 patients.
Oftalmico, Milano; Overall perioperative morbidity rate was 18.5%. Most of them
8Dipartimento di Urologia, Policlinico di Abano, Abano were not serious (haematuria and clot retention) and were
Terme; classified as Clavien type I (42 cases; 75%) or II (8 cases,
9Dipartimento di Urologia, AOU Policlinico Vittorio 14%). Higher grade complications were scarce: CCS IIIb in
Emanuele, Catania; six cases (11%). No TURB related death was reported. Six
10Dipartimento di Urologia, Ifo Regina Elena, Roma, Italy; patients were re-operated due to significant bleeding or clot
11Dipartimento di Urologia, Hospital Universitario Infanta retention on postoperative days 2-7. No significant association
Sofia, Madrid, Spain; between Age, sex, ASA score, anti-coagulant treatment, BMI,
12Dipartimento di Urologia, Ospedale Careggi, Università Di tumor size, number of lesions, diabetes, hypertension,
Firenze, Firenze; ischemic heart disease and hospital stay with the number of
13Dipartimento di Urologia, Università di Bari, Bari; complications were observed. On univariate (73.5±38 vs.
14Dipartimento di Urologia, Istituto Nazionale Tumori, 36.7±21.6 minutes) and multivariate analysis longer operative
Fondazione G Pascale, Napoli; time was the only independent parameter associated with a
15Dipartimento di Urologia, Policlinico di Abano, Abano higher risk of CCS type I complications (OR: 1.040 per
Terme; minute, 95%CI 1.025-1.055, p=0.001). Grade Complications I
16Dipartimento di Urologia, Policlinico di Milano, Milano, 42 II 8 IIIb 6 IV 0 V 0. Conclusion: The modified CCS

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

represents a practical and easily applicable tool that may help intermediate risk patients and in 58.2% of high risk patients.
urologists to classify the complications of TURB in a more Conclusion: Radical prostatectomy remains the “gold
objective and detailed way. In our experience, using this CCS standard” for localised prostate cancer. However, HIFU seems
tool, TURB is a safe procedure with a low morbidity rate. to be a promising alternative and less invasive treatment
Post-operative bleeding is the most significant complication modality with an encouraging success rate, at least in the
that determines a reoperation. A longer operative time is a short-term, in patients with low and medium risk of
significant risk factor for not serious post-operative progression, not candidates for radical surgery; in cancers with
complications. clinical stage >or=T2c, or PSA >20 ng/m L, or Gleason score
higher than 7 seems to get good results in about half of
1 Dindo D, Demartines N and Clavien PA: Classification of patients.
surical complications: a new proposal with evaluation in a
cohort of 6336 patiens and result of a survey. Ann Surg 240: 1 Thüroff S, Chaussy C, Vallancien G et al: High-intensity
205-213, 2004. focused ultrasound and localized prostate cancer: efficacy
2 Mamoulakis C, Efthimiou I, Kazoulis S et al: The modified results from the European multicentric study. J Endourol
Clavien classification system platform for reporting 17(8): 673, 2003.
complications in transurethral resection of prostate. World J 2 Berge V, Baco E and Karlsen SJ: A prospective study of
Urol 29: 205-221, 2011. salvage high-intensity focused ultrasound for locally
radiorecurrent prostate can cer: early results. Scand J Urol
Nephrol 44(4): 223, 2010.
108 3 Ficarra V, Zecchini S, Novara G et al: Short-term outcome
HIGH-INTENSITY FOCUSED ULTRASOUND (HIFU) after high intensity focused ultrasound in the treatment of
IN PROSTATE CANCER IN PATIENTS WITH LOW, patients with high-risk prostate cancer. BJU Int 98: 1193,
INTERMEDIATE OR HIGH-RISK OF PROGRESSION 2006.
Antonio Traficante, Andrea Callea, Roberto Piccinni,
Vito Zizzi, Domenico Sblendorio, Bartolomeo Berardi,
109
Antonio Tempesta, Francesco Giuseppe Gala
NEPHRON SPARING TREATMENT IN THE
Department of Urology di Venere Hospital, Bari, Italy TRANSITIONAL CELL CANCER OF
THE UPPER URINARY TRACT
Objective: HIFU is a minimally invasive treatment based on
Antonio Traficante, Andrea Callea, Domenico Sblendorio,
thermal ablation of tissues which are warmed up to 85˚C in
Roberto Piccinni, Bartolomeo Berardi, Vito Zizzi,
the focal area. Clinical studies have shown such treatment
Antonio Tempesta, Francesco Giuseppe Gala,
modalit y to be safe and effective in the management of
Nicola Fiorentino
localised prostate cancer (1) as well as of local recurrences
after radical prostatectom y or radiotherapy (2), but there are Department of Urology di Venere Hospital, Bari, Italy
still few data in patients with high -risk localised prostate
cancer: clinical stage > o or =T2c or Gleason score 8-10 or Purpose: Nephroureterectomy with excision of a cuff of
PSA >20 (3). Patients and Methods: From May 2 002 to bladder remains the standard for managing upper tract
February 2012, 179 patients with no previous treatment for transitional cell carcinoma, which could, in selected cases, be
prostate cancer, aged 44 to 86 years (mean 75) underwent 206 managed conservatively (1). Patients and Methods: In 12 years
HIFU treatments; 27 patients needed a second treatment as the we have treated 169 reno-ureteral unities (r.u.u.) for urothelial
first was incomplete (4 patients) or because of recurrence (23 tumors; 107 r.u.u. with low-stage and low-grade disease (96
patients). The prognosis subgroups were defined as low -risk patients, 11 with bilateral tumor and 4 solitary kidney), were
in 29 patients (clinical stage T1-T2a, PSA < or = 10 ng/mL treated by an endoscopic approach; in 62 cases (5 for high
and Gleason score lower than 7), intermediate -risk in 47 grade recurrences after conservative approach)
patients (clinical stage T2b or PSA 10-20 ng/mL or Gleason nephroureterectomy was performed. In 107 r.u.u. treated by
score of 7), and high-risk in 103 patients (clinical stage > or = ureteroscopic approach, we observed 5 high-grade recurrences
T2c or PSA >20 ng/mL or Gleason score higher than 7). (nephroureterectomy) and 34 low-grade (G1-G2) recurrences.
Results: At a mean follow -up of 79.3 months, biochemical Each r.u.u. received an average of 2.5 ureteroscopic operative
success rate (PSA constantl y <0.5 ng/ml) was obtained in procedures. The patients were followed up for a mean of 49.9
82.8% of low and intermediate risk patients and in 42.7% of months after initial treatment and currently they are all
high risk patients; post -treatment biopsies (6 months after recurrence free. 11/96 patients with suspect tumor of the upper
treatment) revealed no residual tumour in 92.1% of low or tract (11.4%) had no carcinoma in the ureteroscopic biopsy.

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

Conclusion: Ureteroscopic approach of upper urinary tract values were, respectively 7.09 ng/mL, 1.03 ng/mL, and 6.2%.
urothelial tumors in the current literature has been used Median p2PSA, %p2PSA, and PHI value were respectively,
successfully (2), resulting in recurrence rates ranging from 31% 27.98 pg/ml, 1.62%, 69.83. Overall 34 patients (68.3%) were
to 65% and disease-free rates of 35% to 86% (1). Progression diagnosed with pathological grade Gleason Sum >7; 23
and metastatic rates are low and correlate with tumor grade. patients were diagnosed with pT3 disease. Tumor Volume <0.5
mL was observed in 6 patients. On bivariate analyses,
1 Soderdahl DW, Fabrizio MD, Rahman NU, Jarrett TW and %p2PSA and PHI were accurate predictors of presence of T3
Bagley DH: Endoscopic treatment of upper tract transitional disease, pathological grade Gleason sum >7 and tumor volume
cell carcinoma. Urol Oncol 23(2): 114-122, 2005. Review. <0.5 mL. The p2PSA, %p2PSA and PHI levels were
2 Sowter SJ, Ilie CP, Efthimiou I and Tolley DA: significative higher in patients with pT3 disease. Pathological
Endourologic management of patients with upper-tract Gleason sum >7 (all p value<0.001), respectively 30.50 vs.
transitional-cell carcinoma: long-term follow-up in a single 26.53-1.21% vs. 1.86% - 77.67 vs. 65.23 Conversely in
center. J Endourol 21(9): 1005-1009, 2007. patients with tumor volume <0.5 mL p2PSA and PHI were
significantly lower. Conclusion: In the current study, we
investigated the relationship between p2PSA, PHI and PCa
110 characteristics at final pathology in a group of men treated
PREOPERATIVE P2PSA AND PROSTATE with RP for clinically localized prostate cancer. The results of
HEALTH INDEX PREDICT PATHOLOGICAL the study supported the hypothesis that p2PSA and its derivate
OUTCOMES IN RADICAL PROSTATECTOMY PHI, may predict the final pathological outcomes. Further
FOR PROSTATE CANCER studies are required to externaly validate our finding.
Sisto Perdonà1, Giuseppe Quarto2, Renato De Domenico2,
Guazzoni G, Lazzeri M, Nava L, Lughezzani G, Larcher A,
Domenico Sorrentino2, Ada Marino3, Alessandra Sorrentino3,
Scattoni V, Gadda GM, Bini V, Cestari A, Buffi NM, Freschi
Claudia Mazzarella3, Dario Bruzzese4, Daniela Terracciano3,
M, Rigatti P and Montorsi F: Preoperative prostate-specific
Vincenzo Altieri5, Giovanni Castelluzzo6, Matteo Ferro6
antigen isoform p2PSA and its derivatives, %p2PSA and
1UOC-Urologia, Istituto Nazionale Tumori Fondazione “G. prostate health index, predict pathologic outcomes in patients
Pascale”, Napoli; undergoing radical prostatectomy for prostate cancer. EurUrol
2Urologia, Istituto Nazionale Tumori IRCCS “Fondazione G. 61(3): 455-466, 2012. Epub 2011 Nov.
Pascale”, Napoli; Guazzoni G, Nava L, Lazzeri M, Scattoni V, Lughezzani G,
3Patologia, Clinica Università Federico II, Napoli; Maccagnano C, Dorigatti F, Ceriotti F, Pontillo M, Bini V,
4Statistica, Medica Università Federico II, Napoli; Freschi M, Montorsi F and Rigatti P: Prostate-specificantigen
5Urologia, Università Degli Studi Di Salerno; (PSA) isoform p2PSA significantlyimproves the predictionof
6Urologia, Università Federico II, Napoli, Italy prostate canceratinitialextended prostate biopsies in patients
with total PSA between 2.0 and 10 ng/ml: results of a
Background: In men with prostate cancer, the clinical prospectivestudy in a clinicalsetting. EurUrol 60(2): 214-222,
parameters used such as PSA, digital rectal examination, or 2011. Epub 2011 Apr 5.
biopsy Gleason sum, fail to accurately predict PCa Bessede T and Malavaud B: The new biomarkersof prostate
aggressiveness. Therefore several biomarkers have recently cancer. Prog Urol 21(Suppl 2): S63-67, 2011. French. PubMed
been investigated with promising [Link] objective of this PMID: 21397832.
study is to evaluate the use of prostate-specificantigen (PSA)
isoforms p2PSA, percentage of p2PSA to free PSA (%p2PSA)
and the Prostate Health Index (PHI), in predicting PCa 111
characteristics at final pathology after RP. Patients and ABIRATERONE ACETATE, AN EFFICIENT
Methods: An observational prospective study was performed TREATMENT OPTION FOR ELDERLY
in 63 consecutive men diagnosed with clinically localised PCa PATIENTS WITH METASTATIC CASTRATION-
who underwent RP at our istitution. None of the patients RESISTANT PROSTATE CARCINOMA
included in the current study receved neoadjuvant –deprivation
Lucia Fratino1, Giovanni Lo Re2, Jerry Polesel3,
[Link] determined the predictive accuracy of p2PSA,
Lamia Channoufi4, Davide Santeufemia2, Antonino Ius2,
%p2PSA, and PHI. The primary end point was to determine
Roberto Bortolus5, Michele Spina4, Emanuela Vaccher4,
the accuracy of these biomarkers in predicting the presence of
Antonio Garbeglio6, Salvatore Tumolo2, Umberto Tirelli4
pT3 disease, pathologic Gleason sum <7, and tumour volume
<0.5 ml. Results: The mean patients age was 66.3 yr (75-50), 1Oncologia Medica, Centro Di Riferimento Oncologico,
preoperative median tPSA, fPSA and fPSA-to-tPSA ratio Aviano;

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

2Clinica di Oncologia, Medica Ospedale SMA Pordenone; month FUP to reach –53.9% than the baseline value at 4-
3Epidemiology Centro Rif Oncologico Aviano; month FUP, while alkaline phosphatase started to decrease at
4Clinica di Oncologia, Medica Centro Rif Oncologico the 5-month FUP. Regarding clinical benefit, the Hb levels
Aviano; constantly increased since the first FUP to reach +15.2% at 7-
5Oncologia Radioterapica, Centro Rif Oncologico, Aviano; month FUP. PS and VAS values showed a positive trend after
6Soc Urologia, Ospedale SMA, Pordenone, Italy 1-month FUP. Three pts experienced grade 2 gastrointestinal
toxicities, 1 pts grade 1 metabolic toxicity and 1 pts grade 1
Background: Prostate cancer (PC) is the most common cancer cardiovascular toxicity. None of the pts reported grade 3 or 4
in men in Europe and the United States, and the third leading toxicity. Conclusion: These preliminary data indicate that
cause of death from cancer in European men. Survival of PC abiraterone used in the daily routine is associated with a good
cells is dependent on the activation of androgen receptors, that response rate -in terms of disease control and clinical benefit-
are overexpressed in this tumor. Furthermore, nearly 90% of with acceptable side-effects also in elderly patients. This
PC patients responding to first-line androgen deprivation observation has encouraging implications for the management
therapy (ADT) undergoes rapid progression. This condition is of PC patients and its therapeutic role in CRPC deserves
defined as castration-resistant prostate cancer (CRPC). attention.
Docetaxel based regimens significantly improve survival in
patients with CRPC, and represent the only treatment strategy
approved by FDA. Recently, the results of several studies have 112
confirmed that activation of the androgen receptor is the key DIFFERENT PSA KINETICS AFTER
factor in the continued growth of PC. The landscape for PC BRACHYTHERAPY OR EXTERNAL
treatment has changed with the approval of cabazitaxel, and BEAM RADIATION THERAPY
abiraterone –a drug that significantly reduces androgen IN LOW-RISK PROSTATE CANCER
production by blocking the enzyme, cytochrome P450 17
Alessia Guarneri, Angela Botticella, Andrea Ruggieri,
alpha-hydroxylase. Blockade of androgen production by non
Fernando Munoz, Riccardo Ragona,
gonadal sources has led to clinical benefit in this setting.
Andrea Riccardo Filippi, Umberto Ricardi
Abiraterone (second hormonal therapy) has been shown to
improve survival in patients with CRPC who progressed after Radioterapia I Università Di Torino, Torino, Italy
docetaxel-based chemotherapy. Since cabazitaxel in older men
has been shown to exert both high haematologic and extra- Aim: Due to a slow process of tumor-cell killing, PSA levels
haematologic toxicity rates, we have chosen to treat unfit after radiotherapy (RT) gradually decrease, and PSA remains
elderly patients with CRPC with abiraterone. The aim of this detectable until reaching a nadir value in 2-5 years. Aim of
study was to evaluate the efficacy and tolerability of a the present study is to retrospectively evaluate PSA kinetics in
treatment with abiraterone in elderly cancer patients with a cohort of low risk prostate cancer patients treated either
CRPC with disease progression after docetaxel-based with brachytherapy (BRT) or external beam radiotherapy
chemotherapy. Patients and Methods: 27 elderly (>60 years) (EBRT). Patients and Methods: Clinical records of 150
patients with CRPC were the target of this clinical consecutive low-risk (NCCN risk classification) prostate
investigation. They were consecutively treated, from February adenocarcinoma patients were selected from our database.
2010 to December 2011, within the “compassionate use” Between April 2003 and December 2009, 69 patients
program of abiraterone. Their median age was 72 yrs (range underwent BRT and 81 EBRT. Patients treated with
60-81), and they had the following Gleason scores: 11 (1 pts), androgen-deprivation therapy (ADT) prior to RT, with a
9 (5 pts), 8 (5 pts), 7 (3 pts), 6 (1 pts), 4 (3 pts). 35% of the 27 minimum follow-up >24 months and/or with >4 PSA
pts received more than 2 lines of therapy, and 30% had measurements after RT were excluded. PSA nadir (nPSA),
visceral sites of metastatic disease. Abiraterone was Time to PSA nadir (TnPSA), bounce PSA (bPSA) and Time
administrated at standard daily dose of 1000 mg per os/die in to bounce PSA (TbPSA) were evaluated in the 2 groups by
parallel with prednisone. The study outcome was the using univariate and multivariate analysis. Nadir PSA was
evaluation of: 1) disease control by means of PSA and alkaline defined as the lowest PSA value after RT; bPSA was defined
phosphatase; 2) clinical benefit by means of ECOG PS, as a post-treatment PSA rise >0.4 ng/ml followed by a
hemoglobin level (Hb), and episodes of pain measured by spontaneous decrease to pre-bounce level or lower;
VAS; 3) toxicity according to EORTC criteria. The median biochemical failure (BF) was defined as biochemical relapse
follow-up time was 5 months, and at each follow-up (FUP) according to the ASTRO-Phoenix definition or introduction
visit individual variations (+/–) of PSA, Hb, PS, AP and VAS of ADT. Results: Median age was 67.4 years (range 53-77)
were evaluated as a percentage of the baseline value. Results: in BRT group and 68.9 years (range 56-80) in EBRT group.
The PSA steadily decreased during the FUP, starting at 2- Median pre-treatment PSA value was 6 ng/ml in both groups.

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

A total of 1574 PSA measurements (754 in BRT group and 47 yrs, smoker, with repeated episodes of hematuria. TC:
820 in EBRT group) were recorded after RT. Median follow- “thickening” plaque “of 30 mm of the floor.” TURV: “cr
up time was 51 months (range 24-101) in BRT arm and 55.6 undifferentiated urothelial infiltrating the muscularis, with
months (range 24-99.3) in EBRT arm. Biochemical disease- neoplastic invasion of vascular spaces.” Cystectomy was
free survival (bDFS) was similar for the 2 arms: at 36 months performed in March 2011. Histological report: “cr. urothelial
96.7% (95% Confidence Interval [CI]: 87.3%99.2%) in BRT cells associated with small cr. urothelial high grade,
arm and 98.8% (95% Confidence Interval [CI]: 91.6%- infiltrating the muscularis full thickness “. After adjuvant
99.8%) in EBRT arm (p=0.72). The median time to BF was chemotherapy: the first line (4 cycles) with gemcitabine 1000
31 months (range, 31-90) after BRT and 52.92 months (range mg/sqm + cisplatin 80 mg/m2. Second line protocol
11-72) after EBRT. The median nPSA was 0.18 ng/mL (range ACOCEV: adriablastin 30 mg/sqm + cyclophosphamide 400
0-0.94 ng/mL) in the BRT group and 0.28 ng/mL (range, 0- mg/sqm + vincristine 1.4 mg/m2 + + carboplatine VePesid 60
2.01 ng/mL) in the EBRT group (p<0.001). The median time mg/m2. Results: The small cell cancer of the bladder is an
to the nPSA was longer after BRT than EBRT (38.47 months extremely rare manifestation of neuroendocrine tumors: about
vs. 26.37 months; p<0.01). Twenty-six patients (37.7%) in the 900 cases since 1981. Neurondocrine tumors include
BRT group and 11 patients (13.6%) in EBRT group carcinoid and neuroendocrine tumors are divided into small
experienced a bounce PSA at any time during follow-up (Chi- cell and large cell neuroendocrine tumor. Unlike the lung
square p=0.001). Bounce PSA occurred earlier after BRT bladder rarely gives paraneoplastic syndromes
(median time to bPSA 22 months; range 10-40 months), than (hypercalcemia, S. Cushing, neuropathy) and is rarely pure.
after EBRT (median time to bPSA 31 months; range 9-47 Incidence is approximately 0.7%, three times higher in males
months) (t Student p=0.04). Discussion and Conclusion: In than females, 50 to 70% of patients are smokers, mean age
low-risk prostate cancer patients, PSA kinetics after BRT or 67 years. Diagnosis is usually invasive and shows spread with
EBRT significantly differs. After BRT, lower nPSA values repetitions instrumentally detectable. Characteristics include
and longer TnPSA were expected because of the higher dose gross hematuria (95%), strangury, urethral obstruction,
delivered. Rising PSA levels in the first 24-36 months after infection and irritative symptoms. The pathological criteria
BRT should be considered with caution (nearly 40% of are small, round or oval, scant cytoplasm, high mitotic count,
patients experienced a PSA bounce, and this phenomenon nuclear material finely dispersed, absent or inconspicuous
may cause anxiety and unnecessary start of hormonal nucleoli. Common finding is necrosis and perivascular tissue.
therapy). Longer follow-up time and a larger study population As a neuroendocrine tumor immunostains are essential:
are required to identify an optimal nPSA cut-off after each chromogranin, synaptophysin (>60%), the leu-7, TTF-1
radiation treatment modality. (40%), Other reported indicators include p53 (75%), c-kit
(27%) and EGFR (27%). Comparative studies of genomic
1 Pinkawa M, Piroth MD, Holy R et al: Prostate-specific hybridization show frequent alterations such as genomic
antigen kinetics following external-beam radiotherapy and deletions of 10q, 4q, 5q and 13q, and transposition of 8p, 5p,
temporary (Ir-192) or permanent (I-125) brachytherapy for 6p and 13q. Possible metastases may be diagnosed by CT:
prostate cancer. Radiotherapy and Oncology 96: 25-29, 2010. retroperitoneal lymph nodes, lung, bone and brain. Because
2 Thompson A, Keyes M, Pickles T et al: Evaluating the of the rarity there are no validated therapeutic trials and
phoenix definition of biochemical failure after 125I prostate review of the literature shows that the most common
brachytherapy: can PSA kinetics distinguish PSA failures therapeutic approach is the combination of chemotherapy and
from PSA bounces? Int J Radiation Oncology Biol Phys radical cystectomy and the latter using the same protocols as
78(2): 415-421, 2010. for the respiratory system. Radiotherapy is important in the
treatment of secondary lesions in the brain, bone pain and
neurologic compression. A review of the literature shows that
113 the prognosis is worse for pure carcinomas, compared to the
SMALL CELL CARCINOMA OF THE BLADDER: A mixed ones. In the study by Nabil Ismaili, patients with
CASE REPORT AND REVIEW OF LITERATURE disseminated disease treated with chemotherapy alone,
median survival was not different from those who performed
M. Saccomanni, Vito Alfano
cystectomy and adjuvant chemotherapy (13.7 months versus
Urologia, Ospedale Fra Castoro San Bonifacio, San the 14.8). The worst results were obtained by adopting the
Bonifacio, VR, Italy radical cystectomy alone, as evidenced by the study of Stev et
al. (2004). This is confirmed by a retrospective study of ‘MD
The tumor-small cell represents an extremely rare variant of Anderson Cancer Center in 46 patients, in which the five-year
neuroendocrine tumor of the bladder for which are not survival was increased by 78% in the case of neo-adjuvant
standardized therapeutic trials. Patients and Methods: Woman chemotherapy and cystectomy, compared to only surgical

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

approach (survival less than 36%). In a study of the Mayo (19%) patients, while acute grade 2 genitourinary (GU)
Clinic, cystectomy and chemotherapy have led to a survival toxicity was seen 19/119 patients (15.9%). Three patients
rate of 70% at 2 years and 44% at 5 years. showed grade 3 acute GI and four GU toxicity. At median
follow-up period of 44 months (range 4-123), two patients
(1,6%) had grade 3 late GI toxicity and three (2,5%) had
114 grade 3 late urological toxicity. Despite the retrospective
ADJUVANT HIGH DOSE RADIOTHERAPY nature of the analysis, our data show an improvement both
FOR PROSTATE CANCER: A SAFE in overall survival and biochemical free-survival. Indeed, on
AND FEASIBLE TREATMENT univariate analysis, the actuarial 5-years overall survival was
95%, while the actuarial 5 years biochemical failure free
Sergio Fersino, Vincenzo Frascino
survival was 85%. Discussion and Conclusion: In our
Radioterapia Dipartimento di Bioimmagini e Scienze experience doses ≥70.2 Gy were administered with
Radiologiche, UCSC, Roma, Italy acceptable toxicity grade (>2) late gastrointestinal and
genitourinary toxicities were observed only in 3.3% of
Aim: Local failure after radical prostatectomy (RP) is patients. Furthermore, these results confirm the positive
common in patients with cancer extending beyond the impact of the RT ≥70.2 Gy in patients at high risk of disease
capsule. Two randomized trials demonstrated an advantage recurrence after radical prostatectomy, with an increase of
for adjuvant radiotherapy (RT) compared with a wait-and-see biochemical relapse free survival. However, further follow-
policy (1, 2). However the optimal dose of external beam up is needed to assess the effect on biochemical disease-free
radiotherapy remains controversial. This study aimed at survival and overall survival.
evaluating the feasibility of high dose radiotherapy after
radical prostatectomy in locally advanced and/or positive 1 Bolla M, van Poppel H, Collette L et al: Postoperative
resection margin adenocarcinoma of the prostate. Materials radiotherapy after radical prostatectomy:A randomised
and Methods: A retrospective analysis was conducted on 119 controlled trial (EORTC trial 22911). Lancet 366: 572-578,
men treated with adjuvant radiotherapy after radical 2005.
prostatectomy between 2000 and 2011, because of locally 2 Thompson IA, Tangen CM, Paradelo et al: Adjuvant
advanced stage (pT2-4, pN0-1 and/or positive surgical radiotherapy for pathological T3N0M0 prostate cancer
margins). The volumes to be treated were defined as follows: significantly reduces risk of metastases and improves
pelvic lymph nodes (CTV2), prostatic fossa and the region survival: long-termfollow-up of a randomized clinical trial. J
of seminal vesicles (CTV1). A dose of 45 Gy (1.8 Gy/fx) Urol 181: 956-962, 2009.
was given to the PTV2, followed by a boost to the PTV1 to
a total dose ranging between 64.8 and 71 Gy. Pelvic
irradiation was performed using 3D conformal RT (box 115
technique) in all patients, while boost irradiation was ROLE OF URINARY DIVERSION ON
performed using 3D-RT (box 4) or IMRT (step and shoot; 5 COMPLICATION RATE AFTER RADICAL
coplanar beams 6 MV photons). Acute toxicity was evaluated CYSTECTOMY: RETROSPECTIVE STUDY
according to the RTOG scale, while EORTC-RTOG scale ON A SINGLE-CENTRE COHORT
was used for late toxicity. Biochemical freedom from failure OF 407 CONSECUTIVE PATIENTS
was defined as the maintenance of a serum PSA level ≤0.2
Sandra Belotti, Alessandro Antonelli, Nicola Bastiani,
ng/ml, while freedom from failure was considered as the
Sergio Cosciani Cunico, Claudio Simeone
absence of clinical local recurrence and distant metastases.
Results: The median age was 64 years (range 46-78). The Cattedra di Urologia, Università degli Studi di Brescia, Italy
median follow-up was 44 months (range 4-123). The median
pre-operative PSA level was 9.5 ng/ml, while median post- Introduction: Radical cystectomy (RC) with urinary
operative PSA was 0,1 ng/ml. All patients completed RT. diversion (UD) is the urological surgical procedure with the
Pathological stages were distributed as follows: pT2a: 1 higher rates of morbidity. Aim of this study is to evaluate if
(0.9%), pT2b: 3 (2.5%), pT2c: 12 (10.1%), pT3a: 55 the type of UD influences the risk of postoperative
(46.2%), pT3b: 43 (36.1%), pT4: 5 (4.2%); pN0: 106 (89%), complications. Patients and Methods: At our institution the
pN1: 13 (11%); R0: 40 (33.9%), R1: 78 (66.1%). Adjuvant type of UD is chosen on the basis of the operative risk and
hormonal therapy was prescribed in 78 (65.5%) patients oncological features. Thus, generally, ureterocutaneostomy
because of high risk of failure. Treatment toxicities were (UCS) is reserved to high risk patients, neobladder (NB-VIP
scored according to the EORTC-RTOG scoring scales. Acute technique) to low or intermediate risk patients, affected by
Grade 2 gastrointestinal (GI) toxicity was seen in 23/119 cancer <=cT2/T3a and not involving the prostatic urethra,

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

ileal conduit (IC) to all the other patients. The data of the Table II
407 consecutive patients undergone RC between 2001 and
2011 at our institution have been perspectively stored in a Factor p HR (95%CI) p HR (95%CI)
dedicated DB. Post-operative complications have been
Age (yrs) 0.002 1.035 0.386 1.012
classified according to the Clavien-Dindo system. By a (1.013-1.057) (0.985-1.039)
binary logistic regression, it has been evaluated in uni and
multivariable analysis, which factors were associated with a Male gender 0.613 0.758 -
complication grade 3 or more. Continuous variables have (0.609-0.944)
been reported as mean±standard deviation or median and
interquartile range (25-75), as appropriate. Results: 73 Charlson-
Romano
patients (17.9%) have been submitted to UCS, 223 (54.8%)
score 0.003 0.200
to IC and 111 (27.3%) to NB, and Table I summarizes their
characteristics. 0 referent referent

1-3 0.11 1.844 0.162 1.438

Table I (1.148-2.964) (0.865-2.932)

UCS IC NB p >=4 0.001 2.817 0.085 1.829

(1.518-5.228) (0.921-3.635)
Age (yrs) 74.3±7.8 70.4±8.1 60.6±8.9 <0.001
ASA <0.001 2.434 0.005 1.931
Male gender 74.0% 82.1% 81.1% score 3-4 (1.585-3.737) (1.214-3.069)
(54 pz) (183 pz) (90 pz) 0.312
BMI 0.425 1.011 -
Charson- 2 2 1 0.001 (0.998-1.024)
Romano score (1-4) (1-3) (0-2)
Operative 0.207 0.853 -
ASA score 3 (3-3) 3 (2-3) 2 (2-3) <0.001 time (hours) (0.666-1.092)

BMI 26.1±3.7 26.3±4.3 26.3±3.6 <0.001 LAD 0.589 0.817 -

(0.392-1.703)
Operative 5.00 5.75 6.17
time (hours) (4.50-5.50) (5.25-6.50) (5.50-7.00) <0.001 pT>=3 0.609 0.838 -
(0.636-1.104)
LAD 83.6% 92.7% 88.1% 0.002
(56 pz) (200 pz) (96 pz) UD <0.001 0.007

pT>=3 66.7% 56.0% 35.2% <0.001 UCS referent referent

(46 pz) (121 pz) (37 pz)
IC <0.001 0.373 0.004 0.441
pN+ 25.4% 21.1% 15.7% 0.002 (0.215-0.647) (0.251-0.775)
(17 pz) (46 pz) (17 pz)
NB <0.001 0.260 0.003 0.364
Alimentation 5 7 7 <0.001 (0.140-0.486) (0.186-0.714)
(days) (4-7) (6-9) (6-9)

Hospital stay 22 20 24 <0.001

(days) (15-35) (16-24) (20-29)
Discussion and Conclusion: This study confirms that RC is a
surgical procedure with a high rate of complications (>60%),
severe (grade >=3) in 18.9% of the cases. The factors with an
Overall, 405 events of complications have been registered in impact on this risk have been a high ASA score (3-4) and the
248 patients (60.9% of the cohort), with a median of 1 event UCS as UD. However, the latter conclusion should be
of complication/patient (1-2); the worst complication has been considered cautiously without stating that IC and NB are UDs
grade 1 in 70 patients (28.2%), 2 in 131 (52.8%), 3a in 16 with a lower risk in all the patients, especially in the ones for
(6.5%), 3b in 13 (5.2%), 4a in 7 (2.8%), 4b in 3 (1.2%) and 5 whom UCS is usually reserved. Anyway, from these data it is
in 8 (3.2%). Table II summarizes the results of statistical possible to speculate that IC and NB are at least no more
analysis. morbid than UCS. Finally, we can conclude that the

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

commonly available clinical data are poor predictor of the risk (24/28), 89.2% (25/28) and 92.8% (26/28) respectively. In
of complications after RC. 21/28 cases we observed spontaneous recovery of erectile
function at mean 1.3 months after surgery (range 1-3); two
patients required oral medical therapy (i.e. phosphodiesterase-
116 5 inhibitors). During follow-up 2 patients developed major
PROSTATIC CAPSULE AND SEMINAL SPARING complications: 1 urethral stricture discovered and treated by
CYSTECTOMY: ONCOLOGICAL AND FUNCTIONAL cold endoscopic incision 7 months after PCSSC and 1
OUTCOME. A TEN YEARS EXPERIENCE pyonephrosis due to ureteral reflux treated by nephrectomy 14
months after surgery. Conclusion: In our experience, prostatic
Lorenzo Masieri, Alessandro Ierardi, Saverio Giancane,
capsule and seminal sparing cystectomy can be considered
Federico Lanzi, Claudia Giannessi, Alberto Lapini,
oncogically safe; the saving of prostatic capsule determines an
Andrea Moffa Marchetti, Sergio Serni, Marco Carini
early continence and erectile recovery without increasing the
Clinica Urologica 1 AOU Careggi, Firenze, Italy risk of leaving neoplastic tissue in situ. The accurate selection
of patients represents a crucial phase to reach the best
Introduction: Prostatic Capsule and Seminal Sparing oncological and functional outcome. Our study suggests the
Cystectomy (PCSSC) is a choice for invasive bladder cancer need of multicenter randomized trials to define standard
and for high grade, refractory to conservative therapy, indications and an operative algorithm with regards to tumor
multifocal and quickly recurrent superficial bladder cancer, in features, patients’ performance status and wishes.
patients determined to preserve erectile function and early
continence recovery. The aim of the study is to evaluate
oncological and functional results in our series of patients 117
undergone PCSSC. Patients and Methods: We retrospectively CLINICAL AND PATHOLOGICAL OUTCOME
reviewed clinical and pathological data of 30 consecutive AFTER RADICAL AND NERVE SPARING
patients (mean age 59.4, range 44-73 years) undergone ANTEROGRADE PROSTATECTOMY FOR BIOPTIC
PCSSC with VIP orthotopic ileal bladder reconstruction for GLEASON SCORE ≥7 AND PSA ≥10 NG/ML
transitional cell carcinoma (TCC) histopatologically confirmed
Michele Lanciotti, Lorenzo Lasieri, Claudia Giannessi,
after transurethral resection (TUR-BT). Overall, 19 patients
Saverio Giancane, Federico Lanzi, Gianni Vittori,
(63.3%) underwent surgery at first-dignosed, sporadic, T2
Graziano Vignolini, Andrea Moffa Marchetti,
high-grade TCC; 11 patients (36.7%) had single to multifocal
Alberto Lapini, Marco Carini, Sergio Serni
non-muscle invasive lesions, refractory to intravescical
immunotherapy with BCG. Our exclusion criteria were: Clinica Urologica 1 AOU, Careggi, Firenze, Italy
posterior wall, trigonal, bladder neck or prostatic urethra
involvement and suspected prostatic cancer. Preoperative Objectives: To evaluate long term clinicopathological
staging included: physical examination, PSA, digital rectal outcomes in intermediate to high risk patients but otherwise
examination, chest X-ray, renal function evaluation, CT- clinically localized prostate cancer (PCa) and Gleason score
urography. All cases were restaged according to 2009 TNM (GS) ≥7 disease treated by anterograde radical prostatectomy
classification. Potency and continence were evaluated (ARP), and to analyze the well known predictors of
preoperatively and at months 1, 3, 6, 12 with IIEF-5 and ICIQ progression in this cohort. Methods: We prospectively
male questionnaire. Results: Mean follow-up was (range) 67.7 recruited 183 patients with GS ≥7, preoperative PSA ≥10
(1-132) months. Definitive pathological staging was: 14/30 ng/ml and clinically localized PCa undergoing ARP from 2000
≤T1, 8/30 T2 and 8/30 T3. In 1 case a single lymphnode to 2010, selected from our institutional RP database of 1328
tumoral involvement was found; in 1 patient an incidental patients. The clinical and pathological features were evaluated.
small prostate cancer focus (T1a, Gleason 3+3) was found. Survival analysis was performed using the Kaplan Meier
Two patients died perioperatively due to thrombohembolism, method. Logistic regression was used to determine predictors
one for colon cancer 44 months after PCSSC and five for of unfavorable disease. Results: 51.3% of patients presented a
metastatic TCC (mean time to progression: 34.6, range 9-72 pathological GS 7, while 48.7% resulted 8-10. We obtained a
months; mean cancer specific survival: 34.7, range 6-86 prevalence of 79.8% PCa with extracapsular extension, 20.2%
months). Two patients are currently on follow-up after of patients were N0 at final pathological examination.
chemotherapy with stable residual disease. Overall 26/28 Incidence of positive surgical margins was 20.7% with a
(92.8%) patients completely fulfilled our continence criteria prevalence of pT3-4 (86.9%); 7.1% with concomitant lymph
(no pads) on daytime and 23/28 (82.1%) resulted continent on node involvement. The mean follow-up was 39.1 months
night-time. Continence rates obtained at catheter removal and (median 31.5, range 6-119). The progression free survival rate
at 1,3,6,12 months were 64.2% (18/28), 78.5% (22/28), 87.5% for all patients was 64.8% and 55.1% at 3 and 5 years

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

respectively. Above all 25.7% of patients had biochemical 2Urologia Istituto Nazionale Tumori IRCCS “Fondazione G.
recurrence (BCR) and mean time to biochemical failure was Pascale”, Napoli;
13 months (median 11, range 3-56). Of the 102 patients with 3Endocrinologia, Università Federico II, Napoli;

bioptic GS 7, in 79.4% it was confirmed at the final 4Patologia Clinica Università Federico II, Napoli;

pathological specimen, while in 20.6% there was a higher 5Urologia, Università Federico II, Napoli;

pathological GS (8-10). A statistically significant difference 6Urologia, Università degli Studi di Salerno,

was found in BCR-free survival comparing the 5-year survival 7Statistica Medica, Università Federico II, Napoli, Italy

rates for GS and pTNM. For those with pathologic GS 7 and

8-10,BCR free survival rates were 63.9 and 45.4% respectively Background: Prostate health index (phi) and prostate cancer
(p=0.015), while for those with pT2, pT3a, and pT3b were antigen 3 (PCA3) have been recently proposed as novel
78.3, 68.6 and 28.9% respectively (p<0.0001). Overall, Nerve biomarkers for prostate cancer (PCa). We assessed the
Sparing (NS) technique was performed in 23 patients (12.5%). diagnostic performance of these biomarkers, alone or in
Mean preoperative PSA in the 23 patients with Bilateral or combination, in men undergoing first prostate biopsy for
Monolateral NS RP was 13.3 ng/ml (median 13, range 10.0- suspicion of PCa. Patients and Methods: One hundred and
47.76), mean age was 63.4 (median 64, range 52-78). Bioptic sixty male subjects were enrolled in this prospective
GS was 7 in 91.3% of them, but after final pathological observational study. PSA molecular forms, phi index
examination it resulted equal to 7 in 65.2% patients. (Beckman Coulter immunoassay), PCA3 score (Progensa
Prevalence of organ confined disease was observed 43.5%, PCA3 assay) and other established biomarkers (tPSA, fPSA
while it was 56.5% for ECE, with few cases of seminal vesicle and %fPSA) were assessed before patients underwent a 18-
invasion (21.1%). Only 3/23 patients (13%) presented BCR core first prostate biopsy. The discriminating ability between
with a mean time of 21.3 months (median 24, range 4 – 36). PCa-negative and PCa-positive biopsies of Beckman coulter
Survival analysis according to NS stratification (Bilateral and phi and PCA3 score and other established biomarkers were
Monolateral) didn’t show a significative difference compared determined. Results: One hundred and sixty patients met
to the radical approach (p>0.05). Pathological GS (p=0.02), inclusion criteria. %p2PSA, phi and PCA3 were
pTNM (p<0.005), surgical margin status (p<0.005) and significantly higher in patients with PCa compared to PCa-
lymphnode involvement (p=0.02) demonstrated to be negative group (median values: 1.92 vs. 1.55, 49.97 vs.
predictors of unfavorable disease at univariate logistic 36.84 and 50 vs. 32 respectively, p≤0.001). ROC curve
regression. On the contrary at the multivariate logistic analysis showed that %p2PSA, phi and PCA3 are good
regression preoperative PSA level, bioptic and pathological GS indicators of malignancy (AUCs=0.68, 0.71 and 0.66,
and surgical margin status had no statistically significant respectively). A multivariable logistic regression model
impact on BCR-free survival. The multivariate Cox model consisting of both the phi index and PCA3 score allowed to
showed tumor stage as the only independent prognostic factor reach an overall diagnostic accuracy of 0.77. Decision curve
for BCR, especially seminal vesicle invasion to be the only analysis revealed that this “combined” marker achieved the
independent prognostic factor (p=0.018). Conclusion: Cancer highest net benefit over the examined range of the threshold
specific survival in our study indicated that selected patients probability. Conclusion: Phi and PCA3 showed no
with intermediate to high risk PCa who undergo RP can significant difference in the ability to predict PCa diagnosis
experience a survival benefit, even when NS surgery was in men undergoing first prostate biopsy. However, diagnostic
adopted though men with unfavorable disease fared poorly. performance is significantly improved by combining phi and
PCA3.

118 1 Auprich M, Bjartell A, Chun FK, de la Taille A, Freedland

PHI AND PCA3 SIGNIFICANTLY IMPROVE SJ, Haese A, Schalken J, Stenzl A, Tombal B and van der
DIAGNOSTIC ACCURACY IN PATIENTS Poel H: Contemporary role of prostate cancer antigen 3 in
UNDERGOING PROSTATE BIOPSY the management of prostate cancer. Eur Urol 60(5): 1045-
1054, 2011.
Sisto Perdonà1, Giuseppe Quarto2, Domenico Sorrentino2,
2 Stephan C, Rittenhouse H, Cammann H, Lein M, Schrader
Renato De Domenico2, Federica Cariati3,
M, Deger S, Miller K and Jung K: New markers and
Alessandra Sorrentino4, Daniela Terracciano4,
multivariate models for prostate cancer detection. Anticancer
Claudia Mazzarella4, Ada Marino4, Carla Armellino4,
Res 29(7): 2589-2600, 2009.
Antonio Di Girolamo5, Florestano Montanino5,
3 Filella X, Alcover J, Molina R, Luque P, Corral JM, Augé
Altieri Vincenzo6, Dario Bruzzese7, Matteo Ferro5
JM and Coca F: Usefulness of proprostate-specific antigen
1UOC-Urologia Istituto Nazionale Tumori Fondazione “G. in the diagnosis of prostate cancer. Anticancer Res 27(1B):
Pascale”, Napoli; 607-610, 2007.

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

119 weeks of. After 1 month of treatment, at the end of third cycle,
EXCAVATED LUNG METASTASES IN METASTATIC cough disappeared and patient improved his PS. After 4th cycle
RCC (MRCC): PSEUDOPROGRESSION AS A the CT scan showed a reduction in number and size of all lung
RESPONSE TO SUNITINIB nodules, and the response was greater than 30%, the biggest
lesion was 20 mm. His best response appeared after only 2
Vittorio Ferrari1, Francesca Consoli1, Giuseppina Arcangeli1,
cycles as psedoprogression and his performance score
Francesca Valcamonico1, Vito Amoroso1, Laura Ferrari1,
improved. He had mild adverse events characterized by grade
Giordano Bozzola2, Claudio Simeone3, Edda Simoncini1
1 fatigue, grade 2/3 neutropenia, and grade 1 anemia. He
1Oncologia Medica A. Spedali Civili, Brescia; responded to therapy and had a reduction in the tumor burden,
2Broncopneumologia A Spedali Civili Brescia; and the response was maintained after the dose. reduction
3Urologia, Università degli Studi di Brescia, Italy Conclusion: This case shows that is it necessary to continue
therapy at the maximum dose if the toxicity is not important,
Introduction: mRCC is the most common form of kidney and the presence of excavated lesions at the first CT is an
cancer. Surgical resection remains the treatment of choice for obvious sign of drug activity. Sunitiib is a very active drug in
most patients with mRCC. Although the recent availability of mRCC and a positive correlation between dose- toxicity and
targeted agents has improved outcomes for these patients, it has response is shown.
also increased the complexity of treatments available to
clinicians and these targeted therapies have significantly altered
the management of pts with mRCC. In current guidelines, in 120
Europe, one of the standards first-line therapy, for the good and CORRELATION BETWEEN PCA3 AND
intermediate risk group, is sunitinib a TK Inhibitor. In this PAYHOLOGICAL FEATURES OF RADICAL
report we describe the case of an old patient with mRCC who PROSTATECTOMY SPECIMENS
achieved a particular clinical response with TKI therapy:
Sisto Perdonà1, Giuseppe Quarto2, Renato De Domenico2,
excavated lung lesions. Patients and Methods: A 69-year-old
Domenico Sorrentino2, Daniela Terracciano3, Ada Marino3,
man presented with cough. He had hypertension and a
Alessandra Sorrentino3, Claudia Mazzarella3,
Karnofsky performance score of 90. His physical examination
Carla Armellino3, Mariano Marsicano4,
was negative for peripheral adenopathy, organomegaly, or
Vincenzo Altieri5, Matteo Ferro4
abdominal masses. Diagnostic evaluation revealed normal
laboratory tests. The CT scan of the chest was positive for 1UOC-Urologia Istituto Nazionale Tumori Fondazione “G.
metastatic disease and mediastinal nodes. On a CT scan of the Pascale”, Napoli;
abdomen, he had a 6 cm mass in the middle of left kidney, left 2Urologia, Istituto Nazionale Tumori IRCCS “Fondazione G.

renal hilar lymphadenopathy, and thrombosis of the vena cava. Pascale”, Napoli;
The pt underwent left radical nephrectomy, surrenectomy and 3Patologia Clinica Università Federico II, Napoli;

nodes debulking, The pathological stage was characterized as 4Urologia, Università Federico II, Napoli;

T1bN0M1. The pathology was consistent with Fuhrman grade 5Urologia, Università degli Studi di Salerno, Italy

4, clear cell renal cell carcinoma with sarcomatoid component.

In July 2011, after surgery, his performance score declined to Introduction: Prostate cancer is one of the most common
70. On physical examination, he had decreased breath sounds malignant diseases in men. The PSA testing has increased the
in the lung, and LDH level was slightly elevated. The CT scans diagnosis of prostate cancer, but many men with low-risk
of the chest and abdomen revealed an increase adenopathy in cancer are still treated actively and exposed to potential
the mediastinum, an increase of metastatic lung lesions, but no complications such as incontinece and erectile dysfunction. The
pleural effusion. In August the patient began therapy with aim of this work is to assess the correlations between Prostate
sunitinib 50 mg daily, 4 weeks on, 2 weeks off. In November Cancer gene 3 (PCA3) levels and pathological features of
after 2 cycles of treatment the pt showed very persistent cough radical prostatectomy (RP) specimens, which define cancer
without fever or other symptoms. He had an examination by aggressiveness. Patients and Methods: The analysis included
pneumologist and he began a course of antibiotics for 10 days 63 men with localized prostate cancer, who underwent radical
associated with bronchodilators aerosol drugs. The CT scan of prostatectomy, with a mean age of 64.3 y (52-75 yr). After
the chest showed an increase of the diameter of lung excavated digital rectal examination (DRE), first-catch urine was
metastases (1 lesion increased in diameter from 23 to 37 mm collected from all patients. The PCA3 score was calculated
but with excavation in the middle of 29 mm) and an overall using the Gene Probe Progensa(™) assay. After RP, the PCA3
reduction of metastasis by 10%. We delayed the treatment by scores were correlated to the pathological features of the RP
week because of neutropenia G2/3 until recovery and then we specimens. Results:The mean PCA3 score was 85.06 (3-554),
reduced the dose of sunititib to 37.5 mg/day, 4 weeks on and 2 In this group the mean PCA3 score was statistically significant

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

lower in men with RP Gleason score <7 vs. >7 (60.79 vs. patients undergoing LNU and 42 months for those treated with
105.76) p<0.001, also the PCA3 score was statistically lower ONU. We evaluated in particular cancer recurrence, the site of
in men with pT2a- T2c vs. pT3a-T3b cancer, respectively 66.22 recurrence and survival. Results: We observed local recurrence
vs. 117.82 p<0.001. PCA3 scores correlated significantly with in 3 patients (8.3%) after LNU and 2 after ONU (6.25%). 2
tumour volume, the mean score in tumor <0.5 mL was 26 vs. patients undergone LNU (5.5%) died of metastatic disease at
91 with p<0.01. Conclusion: The present study shows that the 9 and 12 months, 3 patients undergone ONU (9.3%) died of
median PCA3 score was stastistically significantly lower in metastasis at 12, 16 and 23 months. Bladder recurrence was
men with characteristics of indolent prostate cancer. The study observed in 3 patients after ONU and 4 after LNU. The most
also shows, in according with other studies, the relationship frequent sites of cancer recurrence were: local recurrence (3
between the PCA3 score and prostate cancer significance. LUN 2 ONU), 1 laparoscopic port recurrence, 3 regional
PCA3 scores correlate to numerous histoprognostic factors, lymph node recurrences (2 LNU, 1ONU, bladder recurrences
specifically tumour volume and positive surgical margins. (3 LNU, 4 ONU). Conclusion: There were no significant
These results may have a clinical impact in the near future on differences in disease recurrence and even survival rates at 1
the selection of patients eligible to undergo active surveillance and 3 years were not very different between the two
and nerve-sparing surgery. techniques. The grade and stage of cancer affecting the
incidence of metastatic disease, as well as the localization of
1 Durand X, Xylinas E, Radulescu C, Haus-Cheymol R, early disease (pelvis-ureter-both) was a negative prognostic
Moutereau S, Ploussard G, Forgues A, Robert G, Vacherot F, factor, rather than the surgical technique used. There was no
Loric S, Allory Y, Ruffion A and de la Taille A: The value of evidence so that the control was compromised in cancer
urinary prostate cancer gene 3 (PCA3) scores in predicting patients treated with LNU rather than with ONU.
pathological features at radical prostatectomy. BJU Int Jan
5, 2012. 1 Walton TJ, Novara G, Matsumoto K, Kassouf W, Fritsche
2 van Poppel H, Haese A, Graefen M, de la Taille A, Irani J, HM, Artibani W, Bastian PJ, Martínez-Salamanca JI, Seitz
de Reijke T, Remzi M and Marberger M: The relationship C, Thomas SA, Ficarra V, Burger M, Tritschler S,
between Prostate Cancer gene 3 (PCA3) and prostate cancer Karakiewicz PI and Shariat SF: Oncological outcomes after
significance. BJU Int 109(3): 360-366, 2012. laparoscopic and open radical nephroureterectomy: results
3 Klatte T, Waldert M, de Martino M, Schatzl G, Mannhalter from an international cohort. BJU Int 108(3): 406-412, 2011.
C and Remzi M: Agespecific PCA3 score reference values 2 Ariane MM, Colin P, Ouzzane A, Pignot G, Audouin M,
for diagnosis of prostate cancer. World J Urol Aug 30, 2011. Cornu JN, Albouy B, Guillotreau J, Neuzillet Y, Crouzet S,
Hurel S, Arroua F, Bigot P, Marchand C, Fais PO, de la
Taille A, Saint F, Ravier E, Matte A, Guy L, Bruyère F and
124 Rouprêt M: Assessment of Oncologic Control Obtained
ONCOLOGICAL OUTCOMES OF After Open Versus Laparoscopic Nephroureterectomy for
LAPAROSCOPIC AND OPEN TREATMENT Upper Urinary Tract Urothelial Carcinomas (UUT-UCs):
(NEPHROURETERECTOMY) FOR UROTHELIAL Results from a Large French Multicenter Collaborative
TUMORS OF THE UPPER URINARY TRACT Study. Ann Surg Oncol Jun 21, 2011.
3 Favaretto RL, Shariat SF, Chade DC, Godoy G, Kaag M,
Giuseppe Lotrecchiano, Aldo Delle Cave,
Cronin AM, Bochner BH, Coleman J and Dalbagni G:
Vincenzo Tripodi, Enrico De Fortuna,
Comparison between laparoscopic and open radical
Franco Attanasi, Antonio Quaranta, Luigi Salzano
nephroureterectomy in a contemporary group of patients: are
UOC Urologia, Dipartimento di Scienze Chirurgiche, AORN recurrence and disease-specific survival associated with
“G. Rummo”, Benevento Italy surgical technique? Eur Urol 58(5): 645-651, 2010.

Introduction: Currently the treatment of choice in urothelial

tumors of upper urinary tract is nephroureterectomy (NU)
125
performed Open (ONU), but the laparoscopic treatment is now
PREPARATION OF THE URETHRA, BLADDER-
routinely performed as a minimally invasive therapy (LNU).
URETHRAL ANASTOMOSIS, AND FUNCTIONAL
LNU has demonstrated oncologic safety at least equivalent to
AND ONCOLOGICAL RESULTS IN RADICAL
open, but some issues dealing with cancer still remain.
RETROPUBIC PROSTATECTOMY
Patients and Methods: We analyzed data from 36 LNU
performed between 2006 and 2010 retrospective compared Aldo Delle Cave, Giuseppe Lotrecchiano,
with the data of 32 ONU performed in 2002-2005 Enrico De Fortuna, Antonio Quaranta,
(prelaparoscopy era). The mean follow-up was 23 months in Franco Attanasi, Vincenzo Tripodi, Luigi Salzano

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

UOC Urologia, Dipartimento di Scienze Chirurgiche, AORN of a orospective Parallel Group Trial Thomas E. Ahlering
“G. Rummo”, Benevento, Italy European Urology 60(4): 29-36, 2011.
Open versus robotic-assisted radical prostatectomy: which is
Introduction: We retrospectively analyzed oncological and better? Wilson, Timothy; Torrey, Robert Current Opinion in
functional results in a series of 530 patients in our open retro Urology 21(3): 200-205, 2011.
pubic radical prostatectomy. Patients and Methods: From
April 2002 to December 2011, 590 patients underwent RRP
for clinically localized prostate cancer. The mean age of the 126
patients was 64 years (47-74), PSA 1.9 to 46.7 ng / ml. Our ROBOTIC RETROPERITONEAL PARTIAL
surgical technique involves the saving of the pubo-prostatic NEPHRECTOMY FOR RENAL CELL CARCINOMA
ligaments, careful preparation of the urethra with its muscle-
Lorenzo Gatti
aponeurotic structures, which is sectioned prostatic apex,
careful preparation of the bundle for nerve-sparing technique, U.O. Urologia Cattedra e Dipartimento di Urologia, Spedali
saving the bladder neck at the time of vesico-prostatic junction Civili e Università degli Studi di Brescia, Italy
section and eversion of the mucosa,calibrating diameter of
bladder neck on urethra, anastomosis with 5-6 loop suture of Introduction: Robot-assisted partial nephrectomy (RAPN) is
3-0 Caprosyn on 22 Ch Foley catheter, encapsulating all becoming popular, especially at referral institution for robotic
musculoskeletal structures aponeurotic. The bladder catheter surgery. However, even if open partial nephrectomy is
is usually removed at 12˚ day. From January 2010 we have performed via a lumbotomic retroperitoneal access by the
introduced, for the realization of the bladder-urethral majority of surgeons, RAPN is generally made via an anterior
anastomosis, the technique described by Van Velthoven, transperitoneal access, since the vast majority of laparoscopic
performed with a double monofilament absorbable suture in and robotic surgeons are much more confident with it. Here
3/[Link] catheter is removed in the 5-7 day Results: The mean we present a case of RAPN conducted via a retroperitoneal
follow-up was 54.3 months, pathological stage pT2 83%, pT3a access. Patients and Methods: Male, 54 years old, with a BMI
13%, pT3b 7%, Gleason score = or <7 in 78.5%, >7 in of 39.3, who previously underwent open bilio-pancreatic
21.5%.Positive surgical margins were detected in 8.4%, diversion (Scopinaro’s technique) due to pathologic obesity.
negative in 91.6%. 493/530 patients (93%) were completely During the assessments performed to investigate a right renal
continent (no pads), 27 (5%) had mild incontinence (1-2 pads cholic caused by an ureteral stone which required ureteral
daily), 5 (1.8%) were incontinent (>2 pads daily). Continence stenting, a renal mass, 3.1cm in diameter, partially exophytic
was assessed at the catheter removal and 1, 3, 6 and 12 months and located in the posterior face of the lower third of the left
and was 59%, 76%, 88.5%, 91%. In the group Van Velthoven kidney was discovered (RENAL 8P, PADUA 9PM). The
we have observed better results (continence at 1, 3, 6, 12 patient has been submitted to a retroperitoneal RAPN with a
months respectively was 65%, 79%, 86% 94%). Only 9 conventional technique: open retroperitoneal blunt access,
patients (1.7%) developed a vesico-urethral junction sclerosis positioning of 3 robotic trocars along a subcostal line and one
in about 6 months after surgery (nobody in the Van Velthoven 12-mm assistant trocar; docking of the robotic system DaVinci
group), then treated with endoscopic resection. Conclusion: Si; dissection of the psoas muscle; isolation and suspension of
Our technique allows an accurate preparation of prostate apex the main renal artery; isolation of the kidney from its fat and
and urethra, preserving the striated sphincter, the urethral exposition of the tumor; clamping of the renal artery with a
support structures and preserving the maximum length of the dedicated robotic bulldog (ScanLan); enucleoresection of the
urethra. Moreover, the preparation of neurovascular bundles, tumor; renal renorraphy and closure of the parenchymal defect
and the preparation of the bladder neck allows to obtain by sliding clips technique; de-clamping; drainage. Results:
functional optimal results. Furthermore, the introduction of the The operative console time was 160 minutes; the post-
technique of Van Velthoven, in the face of operating time operative course has been uneventful with mobilization in day
comparable with surgical technique to loop suture, allows 1, alimentation in day 1 and discharge in day 6. Histology was
anticipating the removal of the catheter, a better and earlier consistent with a clear cell renal cell carcinoma with negative
continence. margins, 2.8 cm in diameter, pT1a Nx M0 G2. Discussion and
Conclusion: RAPN is gaining popularity, at least in referral
Van Velthoven RF, Ahlering TE, Peltier A, Skarecky DW and robotic centers, and is generally performed via a
Clayman RV: Technique for laparoscopic running transperitoneal access. However, open surgery has been
urethrovesical anastomosis: the single knot method. Urology historically generally performed via a retroperitoneal lumbar
61(4): 699-702, 2003. access, due to its clear advantages mainly regarding the more
Impact of posterior musculofascial reconstruction on early direct approach to the renal artery. Moreover, without entering
continence after robot-assisted radical prostatectomy: results in the peritoneal cavity and keeping close the retroperitoneum,

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the risks of bowel, liver and spleen injury are virtually absent the relationship between PCA3-score value and other
during the procedure, as are all the possible consequences prognostic parameters including grading. Among the whole
coming from local complications (hematoma, urinoma, series we analyzed a subset of patients who had already been
infection) of the post-operative course. The majority of submitted to repeat prostate biopsy after PCA3 test (n=70) and
laparoscopic surgeons are not confident with retroperitoneal eventually to radical prostatectomy (n=47). Relevant patients’
access since they are less intuitive and because this is a virtual characteristics are reported in Table I. Data on PSA,
space that needs to be developed during the first steps of the %freePSA and PCA3-score at repeat biopsy and at radical
operation. Coming from our experience in conventional prostatectomy (RP) according to variation in Gleason grades
laparoscopic renal surgery, in the case here presented of a pure are reported in Table II. PCA3 scores and Gleason score were
posterior renal tumor, a retroperitoneal RAPN gave a strongly associated in the biopsy done after PCA3 test (70 pts,
significant advantage in the suturing, as confirmed by the p<0.001). Meanwhile, the same PCA3 scores were correlated
relatively short time of ischemia, but also in the accessibility to the Gleason’s score at RP (47 pts, p=0.031). In conclusion,
to the kidney and to the tumour, also taken into account the these preliminary data indicate that PCA3 scores are higher in
high BMI of the patient and its history of complex abdominal high Gleason grade patients both at repeat biopsy and RP and
surgery. In a centre with experience in retroperitoneal may therefore assist in the identification of indolent versus
conventional laparoscopy, retroperitoneal RAPN is feasible aggressive prostate cancer cases.
and effective.

Table I. Main patients’ characteristics.

127
Age (median-range) 67 yrs (51-84)
PCA3 SCORE VALUE IS SIGNIFICANTLY
Cancer familiarity
RELATED TO GLEASON’S SCORE ON (positive) 22/209 pts (10.5%)
REPEAT PROSTATE BIOPSY AND RADICAL First biopsy (done) 227/227 pts (100%)
PROSTATECTOMY SPECIMENS Final biopsy (positive) 70/227 pts (30.8%)
Gleason score at 5-7a(3+4): 50/70 (71.4%)
Enrico Bollito1, Stefno De Luca2, Andrea Di Stasio3, repeat biopsy 7b (4+3)-10: 20/70 (28.6%)
Roberto Passera4, Angela Milillo5, Eleonora Duregon6, Gleason score at 5-7a(3+4): 26/47 (55.4%)
Alessandro Fornari6, Francesco Porpiglia3, Radical Prostatetomy 7b (4+3)-10: 21/47 (44.6%)
Donato Franco Randone2, Mauro Papotti6
Final biopsy Final biopsy <0.001
1Pathology, University of Turin at San Luigi Gonzaga Negative Positive
Hospital, Orbassano, Turin;
2Department of Urology, Gradenigo Hospital; PCA3 score (<35) 122 (87.1%) 18 (12.9%)
3Department of Urology, University of Turin at San Luigi PCA3 score (>35) 35 (40.2%) 52 (59.8%)
Gonzaga Hospital;
4Nuclear Medicine, University of Turin at San Giovanni Fisher’s exact test
Battista Hospital;
5Laboratory Medicine Gradenigo Hospeital;
6Department of Pathology, University of Turin at San Luigi
Table II. Patients characteristics by Gleason score at final Bx and at
Gonzaga Hospital, Turin, Italy RP (median-range).

PCA3 score represents the amplification rate of PCA3 gene Bx Bx RP RP

GS GS p* GS GS p*
measured by mRNA copies in prostate cells collected from
≤7 (3+4) ≥7 (4+3) ≤7 (3+4) ≥7 (4+3)
voided urine after digital rectal examination. On a series of up
to 1200 cases (Bollito et al., Anal Quant Cytol Histol, 2012, in PSA 6.01 7.76 0.075 5.56 6.90 0.309
press) we have recently demonstrated a good diagnostic ng/ml ng/ml ng/ml ng/ml
accuracy of this test when applied to patients who had a prior (2.00- (3.60- (2.00- (3.60-
negative prostate biopsy, in order to assess the opportunity of 15.30) 23.00) 14.00) 23.00)
a repeat biopsy. However, some issues are still debated, such %fPSA 14.00 18.00 0.298 12.00 14.00 0.949
(6.00- (6.00- (6.00- (6.00-
as the correlation between PCA3 value and grading of cancer
24.00) 31.00) 24.00) 21.00)
found in subsequent biopsies and radical prostatectomy. In PCA3 55 145 <0.001 62 97 0.031
fact, some Authors reported a significant correspondence (van score (5-160) (48-254) (11-160) (9-254)
Poppel H et al., BJU Int 109(3): 360-366, 2012), while others
(van Gils, Prostate 68(11): 1215-1222, 2008) did not confirm *Mann-Whitney test.

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

128 G2, 0%) and urinary events (G0, 46.6%; G1, 40.8%; G2,
WHOLE PELVIS RADIOTHERAPY IN PATIENTS 12.6%). No patients had rectal late toxicity and only one
WITH HIGH-RISK PROSTATE CANCER patient had an intestinal obstruction after one year from the
end of radiotherapy. Urinary events were observed in 14%
Girolamo Spagnoletti, Rita Marchese,
of patients (G1 for 12.6% and G2 for 1.4%). Median PSA
Anna Maria Leo, Grazia Nardella, Maria Piserchia,
value was 0.1 ng/ml. Thirty-five (49.3%) were still treated
Raffaella Rignanese, Giuseppe Bove
with hormonal therapy at last control. Two patients (2.8%)
Struttura Complessa di Radioterapia Azienda Ospedaliero- experienced biochemical relapse and one had bone
Universitaria, Ospedali Riuniti Foggia, Italy metastasis. The three-year DFS was 81.2%. The three-year
overall survival was 100% since all men were alive at last
Introduction and Aim: Intensity-modulated radiotherapy control. Conclusion: Several studies have shown a survival
(IMRT) seems to reduce the risk of radiationrelated benefit for high-risk prostate cancer patients but whole
toxicities in whole pelvic radiotherapy (WPRT) but not all pelvis radiotherapy continues to be hotly debated. IMRT
patients can benefit to be treated with IMRT. The role of seems to be associated with a lower frequency and severity
WPRT in the management of prostate cancer continues to of side-effects, but our study suggests that also conventional
be an area of controversy. The Radiation Therapy Oncology three-dimensional conformal techniques are well tolerated
Group (RTOG) 9413 Trial (1) showed a progression-free and can offer good results in terms of Biochemical Failure
survival benefit with WPRT in patients with high risk of Rate, DFS and OS with a reasonable acute and late
lymph node involvement but it is also true that WPRT has toxicities.
been associated with high risk of gastrointestinal (GI) and
genitourinary (GU) toxicity. This study aimed at analyzing 1 Roach M, De Silvio C, Lawton V et al: Phase III trial
effects and toxicity of three-dimensional conformal WPRT comparing whole-pelvic versus prostate only radiotherapy
in patients with high-risk prostate cancer. Patients and and neo-adjuvant versus adjuvant combined androgen
Methods: Seventy-nine patients with high risk localized suppression: RTOG 9413. J Clin Oncol 21: 1904-1911,
prostate cancer and >15% risk of lymph node involvement 2003.
(based on Roach et al., 2) were treated with WPRT at the 2 Roach M, Marquez C, Yho H et al: Predicting the risk of
Radiotherapy Department in Foggia between October 2006 lymph node involvement using the pre-treatment prostatic
and February 2011. All patients did not undergo surgery and specific antigen and Gleason score in men with clinically
92.4% of them received hormonal therapy (total androgen localized prostate cancer. Int J Radiat Oncol Biol Phys 28:
deprivation or bicalutamide alone 150 mg/die). For all 33-37, 1994.
patients Clinical Target Volume (CTV) and Planning Target
Volume (PTV) were delineated. CTV1 included the entire
prostate and seminal vescicles with a margin of 6-10 mm to 129
obtain PTV1, while CTV2 included bilateral obturator, MULTIDISCIPLINARY APPROACH IN
external iliac, internal iliac and presacral nodal regions with METASTATIC RENAL CELL CANCER
a margin of 7-10 mm to obtain PTV2. The median dose to (mRCC) WITH SARCOMATOID
PTV2 was 44 Gy (range between 44 and 50) with a daily DIFFERENTIATION: A CASE REPORT
dose of 1.8-2 Gy. The median dose to PTV1 was 72 Gy
Alessandra Mosca1, Alessandro Volpe2, Cristina Bozzola3,
(range between 68 and 80). The organs at risk (bladder,
Davide Gamberoni4, Marco Krengli5, Carlo Terrone2,
rectum, femoral heads and bowel) were contoured and
Oscar Alabiso6
evaluated with respect to dose constraints. The acute and
late GI (rectal and bowel) and GU toxicities were scored 1Oncologia Medica AOU Maggiore della Carità, Novara;
according to the EORTC/RTOG scales. Biochemical relapse 2SCDU Urologia, AOU Maggiore della Carità, Novara;
rate, metastasis rate, Disease Free Survival (DFS) and 3SCDU Anatomia, Patologica AOU Maggiore Della Carità,

Overall Survival (OS) were calculated. Biochemical relapse Novara;

was defined as a nadir PSA value ≥2 ng/ml at least six 4SCDU Ortopedia, AOU Maggiore della Carità, Novara;

months after radiotherapy (ASTRO Consensus Conference 5SCDU Radioterapia, AOU Maggiore della Carità, Novara;

2006). Results: Last controls were performed in December 6SCDU Oncologia Medica, AOU Maggiore della Carità,

2011. Median follow-up was 36 months. Whole-pelvis Novara, Italy

radiotherapy was well tolerated and all patients received the
prescribed dose except for one patient that interrupted his Introduction: Metastatic renal cell cancer (mRCC) with
treatment at 28 Gy. Acute toxicity included rectal (G0, sarcomatoid differentiation is an aggressive disease
77.6%; G1, 21%; G2, 1.4%), bowel (G0, 87.3%; G1, 12.7%; characterized by a relatively high incidence of lung and

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

bone metastases at diagnosis. Median overall survival for 130

these patients is 3-10 months. There is no standard SPONTANEUS REGRESSION OF THORACIC
treatment for this histological subtype, which is associated METASTASES FROM CLEAR CELL RENAL CELL
with poor outcomes to chemotherapy, immunotherapy and CARCINOMA AFTER CYTOREDUCTIVE
targeted therapy. Patients and Methods: We present a case NEPHRECTOMY: CASE REPORT
of a 72-year-old male with diagnosis, on September 2010,
Alessandra Mosca1, Alessandro Volpe2, Cristina Zanzottera3,
of left kidney RCC, Fuhrman grade 3-4, with sarcomatoid
Andrea Palicelli4, Carlo Terrone2, Oscar Alabiso3
and rhabdoid differentiation, and metastatic to bone, lung,
thoracic and abdominal lymphnodes. He was clinically 1Oncologia Medica AOU Maggiore della Carità, Novara;
managed by our multidisciplinary uro-oncologic team, 2SCDU Urologia, AOU Maggiore della Carità, Novara;
represented by Oncologists, Urologists, Pathologists, 3SCDU Oncologia, Medica AOU Maggiore della Carità,

Radiotherapists, Orthopaedists. Results: After Novara;

multidisciplinary clinical analysis and discussion, the 4SCDU Anatomia Patologica, AOU Maggiore della Carità,

patient was first managed by Surgeons, with orthopaedic Novara, Italy

surgery to right ulna for unique bone metastasis, then
submitted to radical cytoreductive left nephrectomy by Introduction: Spontaneous regression of metastatic renal cell
Urologists. Afterwards, he had radiotherapy to right ulna cancer (mRCC) has been reported in some anecdotal
(total 20 Gy). Subsequently, he was submitted by experiences in the literature. The first reported case of
Oncologists to targeted therapies and to bisphosphonates spontaneous regression of mRCC was described by Bumpus
(Zoledronic Acid 4 mg every 28 days), after jaw in 1928. Many of the cases are associated with surgical
osteonecrosis prophylaxis. Concerning systemic treatment, removal of the primary tumor, but regression can also occur
he had first line therapy with Sunitinib 50 mg/die for 4 in association to radiation or embolization of the primary
weeks every 6 (6 months of therapy, with partial response tumor. We present herein a case of spontaneous partial
on lymphnodes), second line therapy with Sorafenib 800 regression of untreated thoracic metastases from RCC,
mg/die (4 months of therapy, with progressive disease), and occurring after cytoreductive radical nephrectomy. Patients
third line therapy with Everolimus 10 mg/die (still ongoing and Methods: A 73 year old man, with excellent performance
since 5 months, with stable disease). Overall survival of status and without relevant medical history, presented at his
this patient is 18 months, longer than initially expected (3- first urological visit for abdomen ultrasound (US) and
10 months). Discussion and Conclusion: Since diagnosis of computed tomography (CT) scan evidence of a left kidney
mRCC on September 2010, several therapeutic strategies tissue mass (65 mm), arising from the middle of the kidney
were applied for this patient, who is still assuming third and consistent with primary renal cancer, and a suspicious left
line targeted therapy, with stable disease, tolerable toxicity adrenal adenoma (12 mm). Urologists indicated staging
and good quality of life. Prospective randomised clinical completion with chest CT scan, which revealed several
trials are necessary to establish the standard treatment for bilateral lung millimetric nodules (maximum diameter 7 mm),
mRCC with sarcomatoid differentiation. As suggested by right pleural thickenings (maximum diameter 16 mm) with
this case report and by our daily clinical activity as a uro- right diaphragm infiltration, and pathological left pulmonary
oncologic team, the multidisciplinary approach can offer hilar lymphnode (20 mm). On December 22 2011, the patient
more chances of treatment to patients, possibly affecting underwent laparoscopic cytoreductive radical left nephrectomy
positively either their response to treatments and their and left adrenalectomy. Histology revealed clear cell RCC,
survival. Fuhrman grade 3, uninjured ureteral margin and left adrenal
gland. No systemic treatment was started by oncologists until
1 Golshayan AR, George S, Heng DY et al: Metastatic post-surgical re-staging with thorax-abdomen CT scan.
sarcomatoid renal cell carcinoma treated with vascular Results: On February 6 2012, 1 month and a half after
endothelial growth factor-targeted therapy. J Clin Oncol nephrectomy, post-surgical CT scan revealed a spontaneous
27(2): 235-241, 2009. partial response of bilateral lung nodules (with reduction of
2 Molina AM, Tickoo SK, Ishill N et al: Sarcomatoid-variant the maximum diameter from 7 to 3.5 mm), a complete
renal cell carcinoma: treatment outcome and survival in regression of all pleural thickenings except for the lesion
advanced disease. Am J Clin Oncol 2010; DOI:10.1097/ which infiltrated right diaphragm and which decreased from
COC.0b013e3181f47aa4. 16 to 7 mm, and a relevant decrease of the pathological left
3 Areses MC, Herranz UA, Ferran BB et al: Temsirolimus in pulmonary hilar lymphnode (from 20 to 8 mm). The Uro-
renal cell carcinoma with sarcomatoid differentiation: a Oncological team decided to defer the start of systemic
report of three cases. Med Oncol 2010; DOI 10.1007/ treatment, planning a subsequent CT scan after 2 months.
s12032011-9976-y. Discussion and Conclusion: The rarity and the heterogeneity

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

of anedoctal cases of spontaneous regression of metastases by lok™ clips. Surgicell™ booster were usually applied on
RCC after nephrectomy do not provide the opportunity to resection area that was also covered by application of
identify the pathophysiologic mechanisms of this Floseal™ or Tachosil™. Results: 10 patients underwent
phenomenon. It has been speculated that the resection of the laparoscopic partial nephrectomy (4 right, 6 left) without
primary tumor may result in removal of growth factors clamping for renal tumour (8 patients) and for renal lithiasis (2
released by the tumor, and even in stimulating the immune patients). Mean age of the patients was 50.9 years (±18.7).
system to control residual disease. It is important to recognize Mean tumour size was 3.7 cm (±1.5). Operative time was 175
the existence of spontaneous regression of metastases in RCC, (±50.4) minutes; blood loss was 435 (±280) ml. Two patients
in order to properly consider surgical intervention and, required blood transfusion. Mean hospitalization was 7.3 (2.8)
subsequently, the appropriate moment to start systemic days. In one patient postoperative urine leakage required
treatment. placing of ureteral stent. Histological evaluation revealed a
Renal Cell Carcinoma in 5 patients, an oncocytoma in 2
1 Lekanidi K, Vlachou PA, Morgan B et al: Spontaneus patients, an angiomyolipoma in 1 patient. All surgical margins
regression of metastatic renal cell carcinoma: case report. J were negative for cancer. Conclusion: Zero-ischemia
Med Case Report 1: 89, 2007. laparoscopic partial nephrectomy without hilar clamping is
2 Melichar B, Vaneckova J, Morakev P et al: Spontaneus feasible and safe. Eliminating global renal ischemia now
regression of renal cell carcinoma lung metastases in a appears achievable. It allows both preservation from ischemic
patient with psoriasis. Acta Oncol 2009 DOI: 10.1080/ renal damage and an excellent control of bleeding.
02841860902882451
3 Rao P, Escudier B and de Baere T: Spontaneus regression of
multiple pulmonary metastases after radiofrequency ablation 132
of a single metastasis. Cardiovasc Intervent Radiol 34: 424- PHOTODYNAMIC DIAGNOSIS OF NON MUSCLE
430, 2011. INVASIVE BLADDER CANCER: PRELIMINARY
EXPERIENCE
Giorgio Napodano, Antonio Campitelli, Tommaso Realfonso,
131
Umberto Di Mauro, Renato Angrisani, Roberto Sanseverino
ZERO ISCHEMIA LAPAROSCOPIC PARTIAL
NEPHRECTOMY. PRELIMINARY EXPERIENCE Urology Umberto I Hospital San Francesco Nocera
Inferiore, SA, Italy
Roberto Sanseverino1,
Olivier Intilla1,
Umberto Di Mauro1,
Giorgio Napodano1, Giovanni Molisso1, Giuseppe Lubrano2
Introduction: Bladder cancer (BC) is the most common
1Urology, 2Anesthesiology, Umberto I Hospital, San tumour of the urinary tract. White light cystoscopy (WLC) is
Francesco Nocera Inferiore, SA, Italy the standard investigation for the diagnosis of bladder tumors.
Recent studies suggest that using exogenous fluorescence
Introduction: Laparoscopic partial nephrectomy (LPN) (PDD) can improve the diagnostic sensitivity and specificity
remains a technically challenging procedure that requires of cystoscopy as well as the radicality of transurethral tumor
advanced laparoscopic skill. Bleeding is one of the most resection (TURB). We report our preliminary experience with
fearful complication of LPN. Warm ischemia time is a PPD, comparing Hexaminolevulinate fluorescence cystoscopy
mainstay issue that could impact on renal function. We report with white light cystoscopy for detecting papillary and flat
our preliminary experience with zero ischemia laparoscopic lesions in patients with bladder cancer. Patients and Methods:
partial nephrectomy. Patients and Methods: A transperitoneal Patients with known or suspected bladder cancer underwent
approach was performed; medialization of colon and bladder instillation with Hexaminolevulinate (Hexvix) (85 mg)
identification of renal vessels. A self made tourniquet was for 1 hour. Cystoscopy was then performed using standard
usually passed around artery without clamping. Renal tumour white light followed by blue light cystoscopy (PPD). Lesions
was identified using Ligasure™ device. In 6 patients we or suspicious areas identified under the 2 illumination systems
performed identification of selective vascular branches that were mapped and biopsied for histological examination (cold
supply tumour blood; selective arterial and venous branches biopsy or TURB). Results: A total of 68 patients (55 male, 13
were clipped with HemOlok™ and then cut. In the remaining female) underwent combined cystoscopy (WL + PPD). 42
4 patients a controlled hypotension was realized to reduce patients had primitive known or suspected bladder cancer
bleeding without clamping. The renal lesion was excised using (group 1), while 26 underwent PPD-Returb for previous
Ligasure™ and cold endoshears. Medullary was repaired with T1HG bladder cancer (group 2). Of group 1 patients, 6 had no
Vicryl™ sutures arrested with absorbable clips. Suture of lesions, 20 had single and 16 had multiple tumours,
cortex was completed with other stitches secured with Hem-O- respectively. Histological evaluation revealed: inflammation (4

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

patients), dysplasia (3 patients), TaG1 (14 patients), T1G1 (2 patients and a positive nodes rate of 40% were registered. A
patients), T1G2 (1 patient), T1G3 (5 patients), T1G3 + CIS (2 small percentage of patients underwent neoadjuvant therapy
patients), CIS (1 patient), T2G3 (4 patients). PPD cystoscopy (14.2%), while 64.3% of patients was subjected to adjuvant
revealed 17 suspected areas in 14 patients: inflammation (4), radio- and hormono-therapy. The biochemical free survival
dysplasia (5), TaG1 (4), T1G3 (1), CIS (3). Of 26 ReTurb rate was 76% and the disease free survival rate was 82.3%.
patients (group 2), 19 presented no lesions, 2 dysplasia, 1 Two cancer-specific deaths were registered during the follow-
TaG1, 1 TaG3, 2 T1G3, 1 CIS. PPD cystoscopy revealed 9 up. Conclusion: We disclose the limits of the study such as the
suspected areas in 6 patients: 1 inflammation, 3 dysplasia, 4 retrospective design and the low number of enrolled patients.
T1G3, 1 CIS. Conclusion: Hexaminolevulinate fluorescence Our results of laparoscopic and robotic surgery are comparable
cystoscopy can be used in conjunction with white light with those of open surgery. We think that pure laparoscopic/
cystoscopy to aid in the diagnosis of bladder cancer. In our robot-assisted radical prostatectomy may offer good results in
preliminary experience HAL fluorescence cystoscopy detected pT3b prostate cancer, being understood that multimodal
at least 1 more tumor than white light cystoscopy in therapy is basic in this setting.
approximately a third of the patients. Whether this would
translate to better outcomes in terms of recurrence and
progression free survival has yet to be determined. 134
METASTATIC COLON CANCER OF THE URINARY
BLADDER: A CASE REPORT
133
Remigio Pernetti, Giorgio Bruno, Fabiano Palmieri,
ANALYSIS OF OUTCOMES OF PROSTATE
Enza Lamanna, Calogero Di Stefano, Salvatore Voce
ADENOCARCINOMA WITH SEMINAL VESICLE
INVASION (pT3b) AFTER PURE LAPAROSCOPIC/ U.O. Urologia Santa Maria delle Croci Hospital, Ravenna,
ROBOT-ASSISTED RADICAL PROSTATECTOMY RA, Italy
Francesco Porpiglia, Cristian Fiori, Matteo Manfredi,
Background: The urinary bladder may be directly invaded by
Marco Lucci Chiarissi, Ivano Morra, Riccardo Bertolo,
tumors of the rectum, prostate, and female genital tract, while
Fabrizio Mele, Massimiliano Poggio, Susanna Grande,
metastases from adjacent or distant organs, via the hematic or
Giovanni Cattaneo, Francesco Porpiglia
lymphatic stream, are rare. Adenocarcinoma as primary
Divisione di Urologia AOU San Luigi Gonzaga, Regione bladder cancer is only found in 0.5-2% of all primary bladder
Gonzole 10, Orbassano, TO, Italy cancers so any adenocarcinoma of the bladder should raise the
suspicion of a distant primary cancer. We report a rare case of
Introduction: The prostate specific antigen era has led to an solitary urinary bladder metastasis from a large bowel cancer,
earlier detection and stage migration, but seminal vesicle presenting a urologic symptom. Case Report: A 69-year-old
invasion is still reported in pathological analysis and remains man was admitted for intermittent gross hematuria. His
a poor prognostic factor. In this study we investigated features medical history included a right colectomy for cancer of the
of disease and outcomes in men with pT3b disease treated in ascending colon. Cystoscopy detected a semi-pedunculated,
our center. Patients and Methods: From October 2001 to non papillary, white-gray mass with focal hemorrhagic areas,
November 2011 we studied 70 patients who underwent grossly spherical in shape, 3.5-4 cm in diameter, situated
laparoscopic or robot-assisted radical prostatectomy for above the front wall of the bladder. A transurethral resection of
prostate cancer with a pathological diagnosis of seminal the neoplastic tissue and of its base was performed
vesicle invasion (stage pT3b). Follow up visits were scheduled subsequently. The histology showed tubular and
at 1, 3, 6 and 12 months. Biochemical- and disease-free pseudoglandular adenocarcinoma type strucures. The
survival were evaluated with post-operative PSA, bone scan malignant cells were very similar to the original colon cancer,
and abdominal CT. Results: The median follow-up was 52 (4- and showed positive staining for CK20+ and Cdx-2+. The
118) months. Mean age of the patients was 63.9 (50-76) years postoperative course was uneventful. The patient is currently
with a mean preoperative PSA of 12.7 (3.7-54) ng/ml. The doing well, with no signs of recurrence, at 24 months after the
35.7% of our population had a positive digital rectal transurethral resection. Discussion: Abdominal or extra-
examination. Median bioptic Gleason Score was 7 (4-9) as the abdominal malignancies very rarely involve the bladder wall
pathological Gleason Score (69). Positive surgical margins as isolated metastases. The mechanism of metastasis to the
were found in 47% of patients, with 68% of them with a >3 urinary bladder, as well as the factors promoting this process,
mm length and 46% at the apex. Three cases of are obscure, although hematogenous and/or lymphatic spreads
neuroendocrine and one of ductal prostatic adenocarcinoma should always be taken into account. Involvement of the
were found. Lymph-node dissection was performed in 71% of bladder can be assessed by ultrasonography, CT scan, MRI,

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

and cystoendoscopy. Detection of an adenocarcinoma in the complications after ultrasound-guided biopsy of the prostate.
bladder should raise the suspicion of a metastatic cancer either A bibliographic search covering the period from January 1990
from a gastrointestinal focus or from the upper urinary tract. A to May 2011 was conducted in PubMed, MEDLINE and
thorough differentiation between the primary enteric type EMBASE. We also included our own series in the analysis.
adenocarcinoma of the bladder and secondary colorectal Results: A total of 3218 participants were included.
adenocarcinoma involving the bladder should be performed, Haematuria was statistically more frequent (p=0.001) among
because these two conditions are morphologically patients taking aspirin than in the control group with an odds
indistinguishable. An immunohistochemical panel including ratio estimate of 1.36 [1.13; 1.64]. This increased risk was,
CK7, CK20, villin, and β-catenin can help the diagnosis, however, due to minor bleeding. The occurrence of rectal
because most lesions of colorectal origin have a CK7 negative bleeding and haematospermia was not statistically increased
profile while showing a CK20-, villin-, and β-catenin-positive (p=0.33 and p=0.24, respectively) in patients taking aspirin
immunoprofile. Locally advanced cancer directly involving the compared to the control group with odds ratios estimate of
bladder wall can be successfully treated by an en bloc partial 1.24 [0.80; 1.93] and 1.52 [0.75; 3.08], respectively.
or total cystectomy. The treatment of secondary Discussion: There is limited information of the relationship
adenocarcinomas, depending on the stage of the primary between continued use of aspirin and haemorrhagic
tumor and on its location, extent, and number of bladder complications after transrectal ultrasound-guided biopsy of the
metastases, can be performed by an open or transurethral prostate. This is the first comprehensive analysis on this topic.
resection, and/or by a combination of chemo- and Conclusion: Continued use of aspirin does not increase the
radiotherapy. Conclusion: The possibility of metastases should risk of overall bleeding or moderate and severe haematuria
be considered in patients with a history of colonic after prostatic biopsy, and thus stopping aspirin before such
adenocarcinoma and an adenocarcinoma of the bladder. The biopsies is unnecessary.
use of an immunohistochemical panel is recommended to
differentiate between primary and metastatic tumors. Solitary
metastases as observed in this case may only require local 136
resection. SURGICAL MARGIN STATUS AFTER
LAPAROSCOPIC RADICAL PROSTATECTOMY:
EXPERIENCE AFTER MORE
135 THAN 400 PROCEDURES
TRANSRECTAL ULTRASOUND-GUIDED PROSTATE
Francesco Porpiglia, Cristian Fiori, Matteo Manfredi,
BIOPSIES IN PATIENTS TAKING ASPIRIN FOR
Susanna Grande, Ivano Morra, Marco Lucci Chiarissi,
CARDIOVASCULAR DISEASE: A META-ANALYSIS
Massimiliano Poggio, Francesca Ragni, Marco Cossu
Stefano Picozzi1, Ercole Negri2, Stefano Casellato1,
Divisione di Urologia, AOU San Luigi Gonzaga, Regione
Giorgio Bozzini1, Cristian Ricci3, Maddalena Gaeta4,
Gonzole 10 Orbassano, TO, Italy
Luca Carmignani1
1Urology Department, University of Milan, IRCCS Introduction: The aim of this study was to analyze the
Policlinico San Donato, San Donato Milanese; surgical margins status of prostatic glands, resected by
2Urology Department, University of Milan, Istituto Clinico laparoscopic radical prostatectomy (RP) for prostate cancer,
Villa Aprica, Como; and to correlate it with biochemical free survival rate (BFSR).
3Biometry and Clinical Epidemiology Unit IRCCS Patients and Methods: The population was selected from the
Policlinico San Donato, San Donato Milanese; database of 405 patients who underwent RP from July 2000
4Department of Preventive, Occupational and Community to December 2009 at our Urology Department with regular
Medicine, University of Pavia, Pavia, Italy follow-up. To isolate the effect of surgical margins on BFSR,
the patients undergoing neoadjuvant or adjuvant therapy were
Introduction: The management of anti-platelet therapy in the excluded from the study. Three-hundred patients matched all
peri-operative period is a source of great concern. The the criteria, 232 of these (77.3%) had negative surgical
dilemma is between whether to stop these agents peri- margins (NSM) and 68 (22.7%) positive surgical margins
operatively in order to reduce the risk of bleeding (PSM). The median follow-up was 68 (24-118) months. We
complications, or to continue them in order not to compromise investigated the prognostic value of PSM regarding the BFSR
the protection they afford against the risk of cardiovascular and regarding the tumour-specific and non specific mortality.
events. Patients and Methods: The aim of this systematic Biochemical recurrence was defined as increase in PSA
review and meta-analysis was to understand whether values above the threshold of 0.2 ng/ml. PSM were then
continued aspirin therapy is a risk factor for bleeding classified: by extension, in <3 mm (77.8%) and >3 mm

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

(38.9%); by location, in apical (44.1%) and not apical tumor growth. There is currently no clinically useful serum
(55.9%); by number in monofocal (77.9%) and multifocal marker for Renal Cell Carcinoma (RCC). In the present
(22.1%). These data were then entered into a multivariate study we assessed the role of three different serum proteins
analysis to assess the weight of each independent prognostic (CA 15-3, CA 125 and 2-microglobulin) as biomarkers for
factor for biochemical recurrence, along with age, RCC as well as any association between tumor marker levels
preoperative PSA, pathological Gleason Score, pT stage, and clinical-pathological parameters. Patients and Methods:
prostate and tumour volume. Results: The BFSR rate was Serum CA 15-3 (0-25 U/ml), CA 125 (0-35 U/ml) and 2-
67.6% for PSM and 88.8% for NSM. A statistically microglobulin (0-2.6 mg/dl) were measured preoperatively
significant difference between the two groups was identified in 212 patients who underwent radical or partial
by univariate survival analysis (p<0.001) and multivariate nephrectomy for RCC. Mean age was 61 (21-86). The
analysis (hazard ratio or HR 3.78, 95% CI 1.91-7.51, patients were classified according to 2009 TNM (pT1 n=146;
p=0.0001). Patients with PSM also showed a worse tumour- pT2 n=24; pT3 n=42). Fuhrman grade was <2 in 138
specific and nonspecific survival compared with NSM, but patients, and >2 in 74 patients; 12 patients had lymph node
this was not statistically significant. According to the metastases and in 10 cases there were visceral metastases.
extension, BFSR was 77.8% in <3 mm PSM and 38.9% in >3 The mean follow-up was 13 months (1-38). Statistical
mm PSM (p=0.003 - univariate survival analysis). In calculations were performed with MedCalc [Link] software.
multivariate analysis, the HR of 5.46 (95% CI 1.42-21.07, Results: Mean pathological tumor size was 5.51 cm (1-20);
p=0.0137) indicates that a PSM >3 mm is the most important 66 patients had a pathological tumor size above 7 cm. Mean
risk factor for biochemical recurrence in our series, level of CA 15-3 was 26,90 U/ml (5.36-139.80), mean level
comparing it with pT (HR 4.54, 95% CI 1.02-20.16, p=0.047) of CA 125 was 18.37 U/ml (2,60223,30) and mean level of
and PSA (HR 3.82, 95% CI 1.11-13.16, p=0.0335). As for 2-microglobulin was 3,72 mg/dl (1.10-41.70). Preoperatively
the PSM location, in our study an apical margin has been 34,9% (n=74) of the patients had abnormal CA 15-3 level,
demonstrated at greater risk of biochemical recurrence in the 7.5% (n=16) of the patients had abnormal CA125 level and
univariate analysis. BFSR was 59% in apical PSM and 77% 25.5% (n=54) of the patients had abnormal 2-microglobulin.
in not apical PSM (p=0.038). This risk lost statistical No significant difference between CA 125 and 2-
significance in multivariate analysis (p=0.06). Regarding the microglobulin values versus tumor size and Fuhrman grade
number, the increased risk due to multifocality, demonstrated was observed. About CA 15-3, statistical significant
by the univariate analysis (BFSR was 73% in monofocal PSM differences resulted for tumor size (<7 vs. > 7 cm;
and 53% in multifocal PSM, p=0.014), was not confirmed in p<0.0001), for Fuhrman grade (<2 vs. > 2; p<0.0001); for
multivariate analysis (p=0.38). Conclusion: We recommend the presence of lymph node metastases (p=0.0026); and
careful evaluation of patients with positive surgical margins visceral metastases (p=0.0001). These results were
with regard to possible adjuvant therapy after radical surgery. confirmed by Pearson’s correlation coefficient for tumor size
The suggestion is stronger if the margin is more than 3 mm. (r=0.4790; p<0.0001) and for Fuhrman grade (r=0.3956;
p<0.0001). The Kaplan-Maier curves showed that Fuhrman
grade (p=0.0021), tumor stage (p=0.0072) and visceral
137 metastases (p<0.0001) were statistically significant
THE DIAGNOSTIC ROLE OF CA 15-3, prognostic factors for progression-free survival (PFS).
CA 125 AND ΒETA2-MICROGLOBULIN Significant differences in PFS of patients with elevated
IN RENAL CELL CARCINOMA serum levels of CA 15-3 (p=0.0003), CA 125 (p<0.0001)
and 2-microglobulina (p=0.0080), compared with patients
Giuseppe Lucarelli1, Saverio Forte2, Antonio Vavallo2,
who had values below the upper reference interval limit were
Monica Rutigliano2, Vanessa Galleggiante2,
also observed. ROC analysis showed a higher value for CA
Carlo Bettocchi2, Francesco Paolo Selvaggi2,
15-3 versus CA 125 and 2-microglobulin as predictor for
Pasquale Ditonno2, Michele Battaglia2
progression (CA 15-3 AUC=0.947 vs. CA 125 AUC=0.763
1Department of Emergency and Organ Transplantation - vs. 2-microglobulin AUC=0.758) (p=0.02). Conclusion: We
Urology, Andrology and Kidney Transplantation Unit found that CA 15-3, CA 125 and 2-microglobulin are
University of Bari; increased to abnormal levels in some patients preoperatively.
2Unit of Urology and Kidney Transplantation, Department of For CA-15-3, elevated serum levels were correlated to
Emergency and Organ Transplantation, University of Bari, clinical stage and tumour grade. Moreover, for patients with
Italy elevated CA 15-3 levels, PFS was significantly shorter than
for patients with normal CA 15-3 values. Studies based on
Introduction: During recent years, there has been increasing larger series are needed to confirm the utility of this
interest in tumor markers for detecting, and monitoring biomarker.

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

138 in time. Conclusion: This meta-analysis emphasized that the

IS SIMULTANEOUS TRANS-URETHRAL two operations could be performed during the same session
RESECTION OF THE BLADDER AND without any negative oncologic results. The resolution during
PROSTATE ONCOLOGICALLY SAFE? the same session of bladder outlet obstruction would improve
A META-ANALYSIS ON 1234 PATIENTS the patients’ quality of life and performing the procedures in
the same session sparing the patients from a further
Stefano Picozzi1, Stefano Casellato1, Giorgio Bozzini1,
anesthesiological maneuvers and the need for a further
Cristian Ricci2, Maddalena Gaeta3, Luca Carmignani1
hospitalization for the surgical resolution of the prostatic
1Urology Department University of Milan, IRCCS obstruction.
Policlinico San Donato, San Donato Milanese;
2Biometry and Clinical Epidemiology Unit, IRCCS

Policlinico San Donato, San Donato Milanese; 139

3Department of Preventive, Occupational and Community INVERTED PAPILLOMA OF THE BLADDER:
Medicine, University of Pavia, Pavia, Italy A REVIEW AND AN ANALYSIS OF THE
RECENT LITERATURE OF 365 PATIENTS
Introduction: It is not unusual to encounter the clinical
Stefano Picozzi1, Brabara Rubino2, Stefano Casellato1,
scenario of a male patient undergoing endoscopic treatment
Giorgio Bozzini1, Luca Carmignani1
for bladder cancer (TURBT) who also needs transurethral
resection of prostate (TURP). The aims of this meta-analysis 1Urology Department, University of Milan, IRCCS
were to understand if it is oncologically safe or advantageous Policlinico San Donato, San Donato Milanese;
to combine the two procedures in terms of subsequent overall 2Pathology Department, IRCCS Policlinico San Donato, San

recurrences with particular interest to that in the prostatic fossa Donato Milanese, Italy
and to understand if some characteristics of the bladder tumors
can influence the recurrence rate. Methods: A bibliographic Objectives: Until the 1970s inverted urothelial papilloma
search covering the period from January 1950 to December (IUP) of the bladder had generally been regarded as a benign
2011 was conducted in PubMed, MEDLINE and EMBASE. neoplasm. However, in the 1980s several reported cases
Meta-analysis approach was applied comparing prostatic fossa suggested their malignant potential including those indicating
recurrences and total recurrences in simultaneous TURBT and malignant evidence, those showing recurrence and those
TURP and control. Also prostatic fossa recurrences and underlining the association with synchronous or metachronous
tumors’ grading and multifocality in patients treated with transitional cell carcinoma. The aim of this systematic review
simultaneous TURBT and TURP were analyzed. To and analysis of the literature from 1990 to date was to
investigate to what extent observational time influenced contribute to the uncertain questions regarding biological
relapses, a random effect meta-regression logistic model based behavior and prognosis of this neoplasm in order to establish
approach was applied. All statistical evaluations were some key points in the clinical and surgical management of
performed using SAS version 9.2. and by RevMan 5.0. A α these lesions. Patients and Methods: Database searches
level of 0.05 was considered as statistically significant. yielded 109 references. Exclusion of irrelevant references left
Results: Overall, there were 1234 participants in the eight ten references describing studies that fulfilled the predefined
studies considered. The study group consisted of 634 patients inclusion criteria. Results: A problem regarding these
and the control group of 600. Mean age was 67.88 and 61.64 neoplasms was the difficulty of obtaining a correct
years respectively in the study and control groups. In the study histopathological diagnosis. The major differential diagnosis
group, on a total of 634 patients, 65 recurrences in the was endophytic urothelial neoplasia including papillary
prostatic fossa appeared. In the control group, on a total of 600 urothelial neoplasia of low malignant potential or urothelial
patients, 58 recurrence in the prostatic fossa occurred. Data carcinoma of low or high grade, while other significantly rarer
did not show a statistically significant difference of recurrence neoplasias included nephrogenic adenoma, paraganglioma,
in the prostatic fossa between patients treated simultaneously carcinoid tumour, cystitis cystica, cystitis glandularis, and
with TURB and TURP and the control group. Meta-analysis Brunn’s cell nests. The size of the lesions ranged from 1 to 50
did not show a statistically significant difference of recurrence mm (mean 12.8 mm). Most cases occured in the fifth and sixth
in the prostatic fossa with the increased grading of the decade of life. The mean age of patients was 59.3 years (range
neoplasms. But there was a statistically significant increased 20-88 years). From the analysis of the literature we can find a
recurrence in patients with multifocal tumors. There was a strong male predominance with a male/female ratio of 5.8:1.
statistically significant reduction of recurrence between The most common sites reported of IUP were the bladder neck
patients treated simultaneously with TURB and TURP and the region and trigone. Of 285 cases included in 8 studies, 11
control group but there was no reduction of the recurrence rate cases (3.86%) had multiplicity. Out of the total 348 patients,

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

six patients (1.72%) had previous history of transitional cell histopatological analysis was found in 10% of patients after
carcinoma of the urinary bladder, five patients (1.43%) had RARP and in 6% of patients after LRP (p=0.09). Overall PSM
synchronous transitional cell carcinoma of the urinary bladder rate was 28.4% in RARP group vs. 29.2% in LRP group
and four patients (1.15%) had subsequent transitional cell (p=0.84). PSM rate in stage II tumours was 34/168 (20.2%)
carcinoma of the urinary The time before recurrence was not in RALP group and 22/153 (14.4%) in LRP group (p=0.16).
more than 45 months (range 5-45 months, mean 27.7 months) The Table shows the results of the comparison between the
after surgery. Conclusion: Inverted papilloma could be different subgroups.
considered a risk factor and it is clinically prudent to exclude
transitional cell cancer when it is diagnosed and a follow-up is
needed if the histological diagnosis is definitive or doubtful. RARP(%) LRP(%) p-value
We recommend a 4-monthly flexible cystoscopy for the first
From 1-100 36 35 0.88
year and then every six months for the subsequent three years.
From 101 to 200 27 21 0.32
Routine surveillance of the upper urinary tract following From 201 to 251 14 28 0.08
inverted papilloma of the lower tract is deemed not necessary.

140 Conclusion: Overall, PSM rate in the two groups was

PURE VERSUS ROBOTIC ASSISTED comparable even if the robotic procedures were performed
LAPAROSCOPIC PROSTATECTOMY: IS THERE A with a significant laparoscopic experience. Not surprisingly
DIFFERENCE IN TERMS OF POSITIVE SURGICAL the number of PSM decreased progressively with the
MARGINS DURING THE “LEARNING CURVE”? experience of the surgeon. Our data do not support the
hypothesis that RARP allows better oncological results than
Cristian Fiori, Marco Lucci Chiarissi, Ivano Morra,
pure laparoscopy (at least in terms of PSM) in the initial
Riccardo Bertolo, Matteo Manfredi, Fabrizio Mele,
learning curve. Limitations of this study include the
Massimiliano Poggio, Susanna Grande,
retrospective design.
Diletta Garrou, Francesco Porpiglia
Divisione di Urologia, AOU San Luigi Gonzaga Orbassano,
TO, Italy 141
DISTRIBUTION OF PODOPLANIN (D2-40)
Aim: The aim of this study was to compare oncological results IMMUNOSTAINING IN PROSTATE GLAND AND ITS
in terms of positive surgical margin (PSM) rate between POTENTIAL DIAGNOSTIC UTILITY
robotic assisted laparoscopic radical prostatectomy (RARP)
Luca Ventura1, Fabrizio Liberati2, Francesco Marampon3,
and pure laparoscopic prostatectomy (LRP). Patients and
Claudio Festuccia4, Mattia Capulli4, Giovanni Luca Gravina3
Methods: We retrospectively analyzed our radical
prostatectomy database. We extracted data of the first 250 LRP 1Unità Operativa Complessa di Anatomia Patologica
(July 2000-June 2006) and the first 250 RARP (September Ospedale San Salvatore, L’Aquila;
2008-February 2012), performed at our Institution by a single 2Unità Operativa di Anatomia Patologica Ospedale San

surgeon (FP). Pre-operative data (BMI, PSA at diagnosis, Camillo de’ Lellis, Rieti;
bioptic Gleason score –GS-), peri-operative data, 3Divisione di Radioterapia e Radiobiologia, Dipartimento Di

histopathological data (prostate volume, tumor volume, Medicina Sperimentale, Università L’Aquila;
percentuage of volume tumor/volume prostate, number of 4Dipartimento di Medicina Sperimentale Università,

removed lymphnodes) and TNM staging data of the two L’Aquila, Italy
groups were compared. Furthermore, rates of overall and stage
II PSM were compared. Finally, we divided the patients of Background: Podoplanin is a transmembrane mucoprotein
each group in three subgroups (procedures #1-100, #101-200, strongly and selectively expressed by lymphatic endothelial
#201-250) to analyze of PSM and compare this between the cells (1). The monoclonal antibody D2-40, directed against
two groups. Results: As regards pre-operative data, PSA at human podoplanin, has proved to be useful in detecting
diagnosis was higher in LRP group (7.6 vs. 9.7, RARP vs. lymphovascular invasion by neoplasms and in quantifying
LRP; p<0.001) and patients with GS at biopsy <7 were 88% lymphatic vessel density in different tumors (1). It represents
in RARP group and 94.4% in LRP (p=0.01). LN dissections an excellent marker of vascular neoplasms with lymphatic
were 17.6% in RARP group and 32.8% in LRP group differentiation, mesothelial and germ cell tumors, but it results
p<0.001). pT2 stage were comparable between the two groups always negative in adenocarcinomas. Podoplanin expression
(67.2% vs. 61.2%,RARP vs. LRP; p=0.16). GS >7 at was also demonstrated in normal cells, such as osteocytes,

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

chondrocytes, follicular dendritic cells, type I alveolar cells, 1 Kalof AN and Cooper K: D2-40 immunohistochemistry – so
myoepithelial cells of the breast (1) and basal cells in the far! Adv Anat Pathol 16: 62-64, 2009.
prostate (2-3). The aim of this study was to investigate the 2 Kanner WA, Galgano MT, Atkins KA. Podoplanin
distribution and features of D2-40 immunoreactivity in tissues expression in basal and myoepithelial cells: utility and
from different prostatic specimens and its potential diagnostic potential pitfalls. Appl Immunohistochem Mol Morphol 18:
utility. Patients and Methods: After routine diagnostic 226-230, 2010.
histopathology examination and reporting, significant paraffin 3 Kuroda N, Katto K, Tamura M, Shiotsu T, Nakamura S,
blocks from 45 selected patients, who underwent needle core Ohtsuki Y, Hes O, Michal M, Inoue K, Ohara M, Mizuno K
biopsy (18 cases), trans-urethral resection (6 cases), simple and Lee GH: Immunohistochemical application of D2-40 as
prostatectomy (6 cases) and radical prostatectomy (15 cases), basal cell marker in evaluating atypical small acinar
were cut to obtain additional slides immunostained with a proliferation of initial routine prostate needle biospy
monoclonal antibody against human podoplanin (clone D2-40, materials. Med Mol Morphol 43: 165-169, 2010.
DAKO A/S, Glostrup, Denmark). Selected cases included
tissue from the different zones of the gland and the main
prostatic diseases, such as adenocarcinoma, PIN, prostatitis, 142
adenosis, hyperplasia and glandular atrophy. Results: A strong ISOLATED SPERMATIC CORD METASTASIS
cytoplasmic immunoreactivity of lymphatic endotelial cells FROM GASTRIC ADENOCARCINOMA
was observed in all cases and used as an internal positive PRESENTING AS AN INGUINAL MASS
control. Prostatic basal cells were also constantly positive, but
Luca Ventura1, Fabrizio Liberati2, Boris Di Pasquale3,
with a slightly less intensity than that observed in endothelial
Mattia Capulli4, Ilde Cicchinelli5, Giovanni Luca Gravina6
cells. A weak positive signal characterized perineurial and
Schwann cells of the peripheral nerves, as well as ganglion 1Unità Operativa Complessa di Anatomia Patologica,
cells within intra- and extraprostatic nervous ganglia. Smooth Ospedale San Salvatore, L’Aquila,
muscle fibers and stromal fibroblasts showed mild 2Unità Operativa di Anatomia Patologica, Ospedale San

immunoreactivity. Basal cells of seminal vesicle epithelium Camillo De’ Lellis, Rieti,
showed moderate positivity, with a patchy pattern of 3Unità Operativa di Urologia, Ospedale San Salavatore,

expression. Blood vessels endothelium, normal and L’Aquila,

hyperplastic luminal cells, as well as PIN and adenocarcinoma 4Dipartimento di Medicina Sperimentale Università,

cells were constantly negative. Discussion and Conclusion: As L’Aquila,

a specific marker of lymphatic endothelium (1), podoplanin 5Unità Operativa Complessa di Anatomia Patologica,

has been used for detecting lymphovascular invasion and Ospedale San Salvatore, L’Aquila,
quantifying lymphatic vessels density in prostate carcinoma. 6Divisione di Radioterapia e Radiobiologia, Dipartimento di

Recent contributions underlined its utility as a basal cell Medicina Sperimentale, Università degli Studi dell’Aquila,
marker, to avoid potential pitfalls in misinterpretation of L’Aquila, Italy
lympatic invasion (2) and in evaluating atypical small acinar
proliferation (3). Our results confirm the value of D2-40 in Introduction: Metastatic tumors of the spermatic cord and the
highlighting lympatics and basal cells, and its role as a paratesticular region are extremely rare (1) with only 22 cases
negative marker of adenocarcinoma and other glandular reported in the literature. They usually originate from primary
lesions. The use of D2-40 in combination with other basal cell tumors of the abdomino-pelvic district and are characterized
markers may be indicated to identify a wider spectrum of by a poor prognosis (1-3). We report a case of isolated
basal cells. The positivity of peripheral nerves and nervous metastasis in the spermatic cord in a patient undergone total
ganglia may be useful in highlighting the invasion of these gastrectomy for carcinoma 2 years before. Patients and
structures by adenocarcinoma cells and in distinguishing Methods: A 60-year-old man presented with a right inguinal
intraprostatic ganglion cells from neoplastic cells. The patchy nodule. Ultrasonography displayed a 22×14 mm
positivity of basal cells in the seminal vesicle may be of help hypoechogenic mass and a total-body computed tomography
to detect portions of seminal vesicle that may be present in a scanning confirmed the finding in the absence of further
core biopsy and to distinguish between normal epithelium of alterations. Past medical history revealed poliomyelitis at the
seminal vesicles and infiltration of the latter by age of 16 months, left nephrectomy for urolithiasis when he
adenocarcinoma glands in radical prostatectomies. In was 27, and a total gastrectomy 27 months before, because of
conclusion, D2-40 immunostaining in prostate specimens a poorly differentiated adenocarcinoma, pT2pN1pMX, treated
helps to identify different cells and structures and may be with postoperative radiotherapy and chemotherapy. Incisional
useful in routine diagnosis, particularly in the limited material biopsy of the inguinal nodule allowed the intraoperative
available in core biopsies. histological diagnosis of adenocarcinoma and was followed by

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

right orchifuniculectomy. Results: Surgical specimen consisted proliferation (ASAP). We reviewed the outcomes of patients
of a testis measuring 6×3.8×3.2 cm with a spermatic cord undergoing a second and a third biopsy, following an initial
measuring 12 cm in length. Histological examination of the diagnosis of HGPIN or ASAP. Patients and Methods: Patients
formalin-fixed specimen showed infiltration of the spermatic diagnosed with HGPIN (group 1) and ASAP (group 2) on the
cord by a poorly differentiated adenocarcinoma, with primary biopsy, routinely underwent a further bioptic
angiolymphatic invasion, without extension to the epididymis procedure. We evaluated prostate cancer detection rate on
and testis. Neoplastic cells were PAS-positive/diastase- rebiopsy of 112 patients with HGPIN and 74 patients with
resistant, immunoreactive for cytokeratin 7 and EMA and ASAP on initial biopsy. We also evaluated predictor factors of
negative for cytokeratin 20, CA125, PSA, β-HCG and AFP. Pca on rebiopsy: age, PSA, prostate volume, PSA density,
The patient underwent additional chemotherapy with transient number of cores, number of positive cores, time to re-biopsy.
benefit, but died of the disease 34 months later (61 months Results: Of 112 patients with HGPIN, 22.3% and 32%
after gastrectomy). Discussion and Conclusion: Primary presented PCa on second and third biopsy, respectively. Of 74
neoplasms of the spermatic cord are relatively uncommon and patients with ASAP, 31% and 40% presented PCa on second
in the majority of cases they are of mesenchymal origin. The and third biopsy, respectviely. Predictor factors of Pca after
occurrence of spermatic cord metastases is an extremely rare HGPIN were PSA and number of cores at first biopsy.
issue, with primary sites usually represented by prostate, Predictor factors of Pca after ASAP were number of cores at
kidney, colon, stomach and pancreas (1, 2). Gastric carcinoma first biopsy and re-biopsy. Conclusion: HGPIN and ASAP are
represents the most frequent primary site in the japanese frequent histopathological findings; in these patients a
literature (3). Our case may be considered rare because of two repeated biopsy is usually recommended. Considering that our
main reasons: the spermatic cord localization as the only sign prostatic cancer detection rate was 29% after HGPIN and 36%
of relapse and the prolonged survival of the patient, as the after ASAP. No extended initial biopsy is a predictor factor of
mean survival after diagnosis in this peculiar condition was 9 cancer after HGPIN. No extended initial biopsy and no
months (1). The latter may be partially explained by the saturation biopsy on re-biopsy are predictor factors of cancer
absence of other secondary localizations at the time of after ASAP.
diagnosis and by the effectiveness of radiotherapy and
chemotherapy.
144
1 Dutt N, Bates AW and Baithun SI: Secondary neoplasms of HEMATURIA ONE STOP CLINIC: FIRST
the male genital tract with different patterns of involvement EXPERIENCE IN ITALY WITH 255 CASES
in adults and children. Histopathology 37: 323-331, 2000.
Luca Carmignani1, Stefano Picozzi1, Stefano Casellato1,
2 Ota T, Shinohara M, Tanaka M, Date Y, Itakura H,
Giorgio Bozzini1, Gianna Pace1, Luca Lunelli1,
Munakata A, Kinoshita K, Hishima T, Koike M and
Massino Cosentino2, Vincenzo Nicosia2
Kitamura M: Spermatic cord metastases from gastric cancer
with elevation of serum hCG-β: a case report. Jpn J Clin 1Urology Department University Of Milan, IRCCS
Oncol 30: 239-240, 2000. Policlinico San Donato, San Donato Milanese;
3 Pozzobon D, Caldato C, Pavanello M and Di Falco G: 2Occupational Healt Department SAIPEM/Medical Dept.

Neoplasia gastrica metastatizzata al funicolo spermatico: a Saipem SPA, Italy

proposito di un caso. Chir Ital 53: 729-732, 2001.
Objectives: Starting from the UK experience, we decided to
test both the feasibility and the advantages of this diagnostic
143 pathway now established in an Italian hospital. We analyzed
PROSTATE CANCER DETECTION ON the outcomes in detecting transitional cell carcinoma (TCC)
REPEATED BIOPSY AFTER HGPIN AND ASAP of the bladder, and other malignant and non-malignant
conditions. Patients and Methods: Between April 2010 and
Giorgio Napodano, Renato Angrisani,
February 2012, 255 patients presenting with hematuria were
Antonio Campitelli, Umberto Di Mauro,
referred to the Hematuria One Stop Clinic (HOSC) at our
Tommaso Realfonso, Roberto Sanseverino
Institution. Each patient underwent a visit, a Urinary Tract
Urology, Umberto I Hospital, San Francesco, Nocera Ultrasound, a Cystoscopy and CT IVP in selected cases
Inferiore, SA, Italy (evidence of alterations or lesions of the renal parenchyma,
presence of stones of the urinary tract, evidence of doubtful
Introduction: Repeated prostatic biopsy is usually or positive urinary cytology). Where a TCC of the bladder was
recommended following a diagnosis of high-grade prostatic diagnosed, the patient underwent TUR-BT. In other cases
intraepithelial neoplasm (HGPIN) or atypical small acinar (stones, BPH etc.) the appropriate therapeutic pathway was

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

followed. Results: 24.32% of patients with hematuria were diagnostic accuracy of each biomarker by AUC calculation. A
found to have a bladder cancer; 20.78% had a urinary stone; potential cut-off level was computed for each biomarker.
1.18% had prostate cancer; 1.18% had a renal cell carcinoma; Results: Thirty-five consecutive patients were entered in this
0.39 had a urachus neoplasm. The mean age was 68.6 yrs. preliminary study. The median PSA was 6.3 ng/ml (mean:
5.8% of the patients (24.2% on patients with TCC of the 19.4, range 0.41-364). An altered prostate was found at digital
bladder) had a G3 disease. The mean time from admission to rectal examination in 13 (37%) patients. Transrectal ultrasound
the HOSC until the operation day, in case of TCC of the gave a median prostate volume of 44.5 cc (mean 48.7; range
bladder, was 11.1 days. The mean access time to HOSC since 15-105cc). Seven patients (20%) had a previous negative
the event of haematuria was 3.88 days. The patient average biopsy and 5 were receiving dutasteride or finasteride. A
satisfaction level, for those referred to the HOSC, was 4.5 (on median number of 12 biopsy cores was obtained (mean: 12
a scale from 1 to 5). Conclusion: The Italian experience of the range 4-24). Prostate cancer was detected in 21 (60%) men.
One Stop Clinic confirms a high rate of bladder cancer ASAP and PIN were detected in 2 more patients respectively.
detection. Furthermore, a high rate of non-malignant Among the 9 considered angiogenetic biomarkers, only leptin
conditions was detected, stressing the importance of the preliminarily shows an interesting diagnostic accuracy with an
HOSC not only as a cancer clinic but as a complete general AUC of 0,714 (Table 1). At a cut-off value of 2166 pg/ml,
urological clinic. We report a shorter waiting time to leptin demonstrates a sensitivity of 74% and a specificity of
operation, especially for bladder TCC G3 patients. It should 75% with a positive predictive value of 85%. Conclusion:
be a mission of all urologists who manage this disease to Only leptin, among the 9 studied biomarkers, showed
ensure that timely and evidence-based treatment is available promising diagnostic accuracy for the detection of prostate
to all patients; this should include education of referring cancer, suggesting the usefulness of further research.
providers within their community about bladder cancer
awareness and the importance of timely referral for evaluation
of haematuria. Table I. ROC curve analysis (AUC).

Angiogenetic biomarker AUC

145 Angiopoietin_2 0.511
SERUM LEVELS OF ANGIOGENETIC Follistatin 0.676
CANCER BIOMARKERS IN MEN UNDERGOING G-CSF 0.658
PROSTATE BIOPSY. PRELIMINARY DATA HGF 0.636
IL-8 0.524
Giuseppe Bronte1, Stefano Caruso1, Marianna Terrasi1, Leptin 0.714
Dario Passalacqua2, Nino Dispensa2, Vincenzo Serretta2, PDGF-BB 0.638
Carlo Pavone2, Antonio Russo1 PECAM-1 0.596
VEGF 0.589
1Oncologia Medica, Dipartimento Discipline Chirurgiche ed
Oncologiche Università di Palermo;
2Urologia Dipartimento Materno-Infantile, Andrologia e

Urologia, Università di Palermo, Italy

146
Background: The reduction of the number of negative prostate RADICAL PROSTATECTOMY FOR PATIENTS
biopsies in patients with elevated serum PSA represents a WITH CLINICALLY LOCALLY ADVANCED
major challenge. Several angiogenetic biomarkers are involved PROSTATE CANCER: RESULTS OF
in carcinogenesis and cancer progression. The aim of our A SINGLE INSTITUTIONAL STUDY
preliminary study was to investigate if their serum levels might
Giansilvio Marchioro1, Alessandro Volpe1,
be related to prostate cancer detection. Patients and Methods:
Roberto Tarabuzzi1, Matteo Vidali2, Monica Zacchero1,
Angiopoietin 2, Follistatin, G-CSF, HGF, IL-8, Leptin, PDGF-
Paolo De Angelis1, Elisa De Lorenzis1, Carlo Terrone1
BB, PECAM-1, VEGF, PTH were the selected biomarkers for
our research. They were measured by BioPlex immunoassay. 1Department of Urology, 2Department of Clinical Chemistry,
As a preliminary step, consecutive unselected patients Maggiore della Carità Hospital, University of Eastern
undergoing prostate biopsy for palpable prostate nodule and/or Piedmont, Italy
elevated PSA levels were entered. A 12-core transrectal biopsy
was planned. The serum levels of the above mentioned Introduction: Aim of this study was to report the outcomes of
biomarkers were related with the histological result of the a single institution study on 98 pts with clinically locally
biopsy. ROC curve analysis was exploited to test the advanced prostate cancer (PCa) and prostate specific antigen

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

Figure 1. Cancer specific survival. Figure 2. Over all survival.

(PSA) ≥20 ng/ml who underwent radical prostatectomy (RP) 2 Gontero P, Marchioro G, Frea B et al: Is Radical
and pelvic lymphadenectomy (PNLD). Materials and Prostatectomy Feasible in All Cases of Locally Advanced
Methods: We performed a retrospective review of PCa patients Non-Bone Metastatic Prostate Cancer? Results of a Single-
who had initial PSA values above 20 ng/ml and were treated Institution Study. Eur Urol 51: 922-930, 2007.
with surgery between 2000 and 2005. Biochemical recurrence 3 Hsu CY, Joniau S, Oyen R, Roskams T and Van Poppel H:
was defined as a double rise in PSA levels over 0.2 ng/ml after Outcome of surgery for clinical unilateral T3a prostate
RP. Adjuvant or salvage radiotherapy (RT) or hormonal therapy cancer: a single-institution experience. Eur Urol 51(1): 121-
(HT) were indicated according to institutional protocols. 128, discussion 128-129, 2007. Epub 2006 Jun 9.
Overall (OS), cancer specific (CSS), clinical progression free
(CPFS), and biochemical progression free survival (BPFS)
were calculated for the entire cohort and select subgroups using 147
the Kaplan-Meier method with log rank test and Cox WHOLE PELVIS VERSUS PROSTATE ONLY
multivariate analysis. Results: Mean age was 66 years (range 3D-CONFORMAL RADIOTHERAPY IN
IQR 61.8-71). Mean PSA was 30.4 ng/ml (range IQR 24.4-45). PATIENTS WITH PROSTATE CANCER:
PCa was clinically locally advanced in 69% of cases. A RETROSPECTIVE COMPARISON
Pathological staging identified locally advanced disease in
Girolamo Spagnoletti, Rita Marchese, Grazia Nardella,
72.4% of cases (27.6% pT3a, 30.6% pT3b, and 14.3% pT4).
Anna Maria Leo, Giorgia Cocco, Vincenzo Oriolo,
Positive surgical margins and lymph node involvement were
Giuseppe Bove
observed in 68% and 23% of cases, respectively. Mean follow-
up was 65.3 months (range IQR 46.0-96.5). Adjuvant RT and Struttura Complessa di Radioterapia, Azienda Ospedaliero,
HT were administered in 51% and 69% of cases. OS, CSS and Universitaria Ospedali Riuniti, Foggia, Italy
BRFS at 5 (and 10) years were 85% (55%), 93% (71%) and
53% (36%), respectively (Figures 1, 2). Conclusion: RP is an Aim: The role of elective irradiation of pelvic lymph nodes is
effective first step in a multimodality approach for locally an issue that continues to be hotly debated in the radiotherapy
advanced PCa, with convincing cancer-related outcomes. treatment of prostate cancer. Our retrospective study aims to
Patients with PSA ≥20 ng/ml should be considered for an compare whole pelvis radiotherapy (WPRT) and prostate only
aggressive approach, starting with radical surgery. Most radiotherapy (PORT) as regards prognostic factors, toxicities
patients need adjuvant HT or RT. This study confirms that RP and dosimetric aspects. Patients and Methods: From October
should be considered as the first step in a multimodality 2006 to February 2011, 220 men affected by prostate cancer
approach for clinically locally advanced PCa. underwent radical radiotherapy at the Radiotherapy
Department in Foggia. They were treated with multiple 10-
1 Van Poppel H and Joniau S: An Analysis of Radical 18MV beams and three-dimensional conformal techniques.
Prostatectomy in Advanced Stage and High-Grade Prostate PORT included the entire prostate with or without seminal
Cancer. Eur Urol 53: 253-259, 2008. vescicles. WPRT included also bilateral obturator, external

1936
 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

iliac, internal iliac and presacral nodal regions. PORT doses 148
ranged between 68 and 80Gy. WPRT doses ranged between PSA DECREASE IN PATIENTS WITH CASTRATE
44 and 50Gy and were followed by a boost on the prostate RESISTANT PROSTATE CANCER TREATED WITH
volume. For each patient, age, pre-treatment PSA, Gleason DEGARELIX
score and radiation doses were recorded. Toxicity was
Alberto Bonetta
assessed according to the time of onset (acute or late toxicity)
and the organs at risk involved (genitourinary or rectal and Radioterapia Oncologica, Istituti Ospitalieri di Cremona,
intestinal toxicity); the EORT/RTOG scales were used. Italy
Results: Median and minimum follow-up were 36 and 12
months, respectively. Regardless of risk classification, 159 Introduction: Patients with metastatic prostate cancer no
patients (pts) underwent PORT and 61 WPRT. There was a longer responsive to treatment with LH/RH agonist (or
strong association between class of risk and irradiated volumes second-line therapies such as estramustine, estrogens, or
(p<0.01) and a very significant difference of Gleason score ketoconazole) are often treated with docetaxel-based
and pre-treatment PSA values between PORT and WPRT chemotherapy. Recently, the introduction of LH/RH
groups (p<0.01): PSA and Gleason score were important risk antagonists seems to offer a further line of therapy in patients
factors guiding radiation oncologists to WPRT. On the with low levels of testosterone but with PSA progression,
contrary, there was no age difference in PORT and WPRT before chemotherapy. At the Radiotherapy Unit of Cremona,
groups (p=0.5): age at diagnosis did not show to be a variable Degarelix is prescribed in patients with castration-resistant
according to which pts were referred for WPRT or PORT. As prostate cancer refusing chemotherapy with taxotere. Patients
regards total radiation doses, a difference between the two and Methods: From June 2011 to 2/2012 seventeen patients
groups was outlined (p=0.01): when tissues have already with metastatic and castration resistant prostate cancer
received a considerable proportion of dose during irradiation (refusing chemotherapy, were treated with Degarelix. Ten
of the pelvis, it is more difficult to deliver high doses to the patients had previously undergone three therapeutic lines (total
prostate remaining within tolerance constraints for organs at androgen blockade -BAT-, estramustine and ketoconazole),
risk. By analyzing the various types of toxicity, it was noted four with two lines (BAT and estramustine) and three with
that 59% of pts undergoing PORT had acute toxicity vs. 64% only one line (BAT). All patients had detectable testosterone
of pts undergoing WPRT (p=0.51), 11% of pts who underwent values, but below 50 ng/dl, limit of castration. The patients
PORT manifested late toxicity vs. 10% of pts receiving WPRT underwent treatment with monthly injection, for a minimum
(p=0.75), 49% of pts undergoing PORT complained disorders period of 2 months, up to PSA progression. Results: The
of the urinary sphere vs. 47% of pts that received WPRT therapy was generally well tolerated with the appearance of
(p=0.84), 17% of pts receiving PORT reported rectal or asthenia in four patients, two of which even with lack of
intestinal side-effects vs. 31% of pts that received WPRT appetite. Ten patients (52.9%) had a progression of PSA after
(p=0.02): this association between intestinal toxicity and 2 doses of degarelix, therefore the treatment was discontinued.
WPRT can be easily explained by the greater portion of bowel Three patients (17.6%) showed stabilization of PSA values
exposed to radiation during WPRT (p<0.01). Because of the (decrease lower than 30%), with a median response of 2
long natural history of disease and the short follow-up, our months. Five patients (29.5%) showed a significant fall of the
series does not allow to draw results about the effectiveness of PSA (>30% of initial value) with a median response of 4.5
WPRT vs. PORT. Discussion and Conclusion: Arguments exist months (range 3-7 months). Discussion and Conclusion:
for and against the use of prophilactic irradiation of pelvic GnRH antagonists induce castration by a different mechanism
lymph nodes in prostate cancer management. Our series shows to that of GnRH agonists, blocking GnRH receptors and
that WPRT and PORT are two therapeutic alternatives routinely causing an immediate blockade of LH and FSH secretion.
used in the radiation treatment of pts with intermediate-high Because of these different modes of action, degarelix could be
risk prostate cancer. However the final answer on WPRT is not active following previous hormone treatments, as we can see
known and requires further studies. Meanwhile, on the one when bicalutamide/cyproterone acetate shift is performed.
hand radiation oncologist should consider the ease of execution Miller reports 17% of responders to degarelix, when it is used
of PORT, the lower intestinal toxicity expected from PORT and after LH/RH agonists. In our series responders after BAT and
its possibility of delivering a higher dose to the prostate when other hormone treatments were about 30% (47% with disease
a 3D-conformal technique is used; on the other hand WPRT stabilization). At the time, the percentage of response appeared
should be taken into account with the worsening of prognostic high enough to consider degarelix among the possible
factors, especially pre-treatment PSA and Gleason score. A treatments. In view of the cost of the drug, further studies are
large and homogeneous randomized trial will clarify the needed to identify the subgroup with good probability of
usefulness of pelvic irradiation in selected patients with response to treatment among the patients with castration-
clinically localized prostate cancer. resistant disease, before chemotherapy.

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

1 Raddin RS, Walko CM and Whang YE: Response to Notwithstanding a very low caseload and the inclusion of the
degarelix after resistance to luteinizing hormone-releasing learning curve cases, RALP allowed to achieve acceptably
hormone agonist therapy for metastatic prostate cancer. good oncological and functional outcomes with improved
Anticancer Drugs 22(3): 299-302, 2011. blood loss, hospital stay, catetherization time but a longer
2 Crawford ED et al: A phase III extension trial with a 1-arm operative time as a main draw back.
crossover from leuprolide to degarelix: comparison of
gonadotropin-releasing hormone agonist and antagonist
effect on prostate cancer. J Urol 186(3): 889-897, 2011. Table I
3 Miller K: Open-label, exploratory study of degarelix as
RRP RALP p
second-line hormonal therapy in patients with prostate
cancer (CS27),DEG/01.04.10/PM. EAU, Barcelona 2010. Age (mean±DS) years 65.9±6.2 63.4±5.8 0.03*
PSA (mean±DS) ng/dL 7.4±4 6.9±3.4 0.5*
By optical Gleason score (mean±DS) 6.36±1.7 6.1±1.7 0.5*
149 Pre-operative Hb (mean±DS) g/dL 15±1.23 15±1.15 0.8*
ROBOTIC-ASSISTED LAPAROSCOPIC VS.
OPEN PROSTATECTOMY IN A CENTER
Table II
WITH LOW VOLUME OF CASES:
THE EXPERIENCE OF A SINGLE SURGEON RRP RALP p
Marco Oderda, Francesca Peraldo, Francesco Soria,
Nerve sparing
Simone Giona, Alberto Gurioli, Giovanna Berta,
No 41% 55.7% 0.228˚
Andrea Zitella, Alessandro Greco, Paolo Gontero Monolateral 35% 21.2%
Division of Urology-1, San Giovanni Battista Molinette Bilateral 24% 23.1%
Lymphadenectomy
Hospital, University of Turin, Torino, Italy
Yes 61.5% 23.1% <0.01˚
No 38.5% 76.9%
Introduction: We assessed the outcomes of robotic-assisted Operative time (mean±DS) minutes 172±34 276±36 <0.001*
laparoscopic prostatectomy (RALP), including the learning Post-operative Hb (mean±DS) g/dL 11.6±1.4 12.2±1.5 0.03*
curve, compared with those of open retropubic radical Hospital stay (mean±DS) days 8.4±3.5 6.9±2.5 0.01*
prostatectomy (RRP) in the peculiar setting of a single center Catetherization time (mean±DS) days 15.8±4.3 10.3±5.7 <0.001*
with a low caseload. Patients and Methods: 52 consecutive Pathological stage
organ confined 61.5% 65.4% 0.68˚
patients underwent RALP between September 2007 and
not organ confined 38.5% 34.6%
January 2012, carried out by a single experienced open surgeon Pathological Gleason score (mean±DS) 7±0.5 7±0.6 0.8*
with no experience of pure laparoscopic prostatectomy. We Number of node removed (mean±DS) 18±8.7 12.2±7.1 0.04*
compared these cases to 52 patient who underwent RRP in the Positive surgical margins 28.8% 23.1% 0.5˚
same period, performed by the same surgeon, in the same Continence rates at 27 months 87.8% 87.2% 0.9˚
center. The baseline characteristics of the two groups were Time to continence (mean±DS) months 3.9±5.4 3.8±4.3 0.9*
equivalent. We prospectively evaluated the tumour’s Potency rate at 27 months
(nerve sparing surgery only) 29% 21.7% 0.5˚
characteristics, perioperative parameters and early surgical,
Adiuvant or salvage therapy need 23% 15.4% 0.3˚
functional and oncological outcomes of both groups. Results:
Mean follow-up was 27 months. Table I shows baseline *Not paired T-Test; ˚Chi-Square.
patients’ characteristics while Table II shows pathological
results and oncological and funtional outcomes. Discussion:
Our data confirm comparable functional and oncological
outcomes with only significant difference in operative time, 150
post-operative haemoglobin values, hospitalization time and VITAMIN D RECEPTOR GENE POLYMORPHISM
catetherization time. The learning curve and the low volume of IN PROSTATE CANCER AND BENIGN
cases do not affect functional outcomes. The main advantage PROSTATIC HYPERPLASIA
of RALP is, as previously reported, reduction in blood loss,
Roberto Sanseverino, Giorgio Napodano
catetherization time and hospital stay. Moreover there are no
differences in positive margins rate, continence rate and time UOC-Urologia, Umberto I Nocera Inferiore, Italy
to continence. Approximatively 25% of patients having a nerve
sparing surgery will gain full or partial potency with only oral Background: The prostate cancer (CaP) is among the most
therapy in both groups after one year. Conclusion: commonly diagnosed cancers, accounting for about 20% of all

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

newly diagnosed cancers. Subject of recent studies is the role 1Division of Urology Cremona Hospital, Cremona;
of vitamin D in the pathogenesis of CaP. Literature data 2Division of Urology-1, Fidenza Hospital, Parma, Italy
speculated a role of vitamin D in the progression of Cap. In
addition, several studies have shown an association between Introduction and Objectives: Fuzzy system and neural network
VDR gene polymorphism FokI and CaP especially in the are complementary technologies in the design of adaptive
Asian population. Objective: The aim of this study was to intelligent system. Artificial neural network (ANN) learns
compare two populations: CaP vs. benign prostatic hyperplasia from scratch by adjusting the interconnections between layers.
(BPH), to study both the potential role of serum 25-OH A Neuro-fuzzy system is simply a fuzzy inference system
vitamin D (25(OH)D3) and assess the relationship between trained by a neural network-learning algorithm. The aim of our
serum 25(OH)D3 and VDR gene polymorphisms FokI and work was to develop a Neuro-Fuzzy system to predict high-
TaqI and between polymorphic sites and the risk of developing grade prostate cancer (Gleason sum of 7 or more) (HG PCa).
cancer. Material and method. Two hundred patients (aged 41 Materials and Methods: We retrospectively reviewed 1521
to 83 years) in whom biopsies revealed CaP or BHP were patients who underwent prostate biopsy. All men had a PSA
enrolled in the present study. The concentration of 25(OH)D3 level of 50 ng/ml or less. Of the 1521 men, 473 (31%) were
was measured by chemiluminescence immunoassay and diagnosed with prostate cancer on biopsy, and 262 (17.2%)
polymorphisms were detected by PCR-restriction fragment had HG Pca. A neuro-fuzzy system was developed using a
length polymorphism (RFLP). Results: The results showed a coactive neuro-fuzzy inference system model. The model was
significant association (p=0.002) between the genotype FF composed of an input layer with four neurons (PSA, percent
FokI polymorphism, responsible for the translation of a shorter free PSA, PSA density and age), and an output neuron
protein and therefore more functional than normal, in the BPH representing the risk of HG PCa. The fuzzy control method
population compared to CaP, as well as the genotypes of the was the TakagiSugeno-Kang and each input was specified to
TaqI polymorphism (p=0.009). Serum 25(OH)D3 did not show consist of 4 bell membership functions. The number of
significant correlation with respect to polymorphisms and training epochs was 1000. The cases were random divided in
compared to disease, although the concentration was low (<30 train-test group (1000 cases) and validation group (521 cases).
ng/mL) in 97% of the analyzed samples of the two Results: In the validation group the area under the curve
populations. Conclusion: Concluding the CaP is associated (AUC) for the neuro-fuzzy system output was 0.751 +/0.032
with a less functional VDR variation due to a lower frequency (95% confidence interval 0.712 to 0.788), for PSA was
of the genotype FF and for the first time there was evidence 0.594±0.035 (95% confidence interval 0.550 to 0.636) and for
that the tt genotype of TaqI polymorphism (synonymous percent free PSA was 0.690±0.028 (95% confidence interval
polymorphism) is associated negatively to the disease. 0.672 to 0.752). Furthermore, pairwise comparison of AUCs
evidenced differences among PSA, percent free PSA and PSA
Uitterlinden AG, Fang Y, Van Meurs JB, Pols HA and Van density versus neuro-fuzzy system (PSA versus neuro-fuzzy
Leeuwen JP: Genetics and biology of vitamin D receptor system’s output, p=0.001; percent free PSA versus neuro-
polymorphisms. Gene 338(2): 143-156, 2004. Review. fuzzy system’s output, p=0.005). Conclusion: We constructed
Habuchi T, Suzuki T, Sasaki R, Wang L, Sato K, Satoh S, a neuro-fuzzy system based on both serum data and clinical
Akao T, Tsuchiya N, Shimoda N, Wada Y, Koizumi A, Chihara data (age, total PSA, %free PSA, and PSA density) to identify
J, Ogawa O and Kato T: Association of vitamin D receptor men at risk of harboring high grade prostate cancer. It may
gene polymorphism with prostate cancer and benign prostatic assist patients and clinicians in deciding whether further
hyperplasia in a Japanese population. Cancer Res 60(2): 305- prostatic evaluations are necessary.
308, 2000.
Makariou S, Liberopoulos EN, Elisaf M and Challa A: Novel
roles of vitamin D in disease: what is new in 2011? Eur J 152
Intern Med 22(4): 355-362, 2011. Epub 2011 May 31. Review. PERCUTANEOUS MICROWAVE TREATMENT OF
SMALL RENAL TUMOURS: CLINICAL AND
PATHOLOGICAL ASPECTS
151 Stefano Guercio, Mauro Mari, Francesco Mangione,
SOFT COMPUTING FOR PREDICTING Alessandra Ambu, Francesca Vacca,
HIGH GRADE PROSTATE CANCER Claudia De Maria, Maurizio Bellina
Luigi Benecchi1, Michele Potenzoni2, Matteo Quarta1, Urologia Ospedale degli Infermi di Rivoli, Italy
Laura Perucchini1, Fabrizio Russo1, Mario Tonghini1,
Anna Maria Pieri2, Carmelo Destro Pastizzaro2, Aim: In this study we evaluated the safety and effectiveness,
Carlo Del Boca1 based on a clinical and pathological follow-up, of the

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

treatment with percutaneous microwave of small renal possible efficacy of percutaneous microwave ablation of
tumors in selected patients (with comorbid disease or small renal tumors in selected patients. The radiological
advanced age). Patients and Methods: From January 2010 assessment alone may not be sufficient to evaluate the
to December 2011, 12 patients (11 men, 1 woman) with effectiveness of minimally invasive techniques in the
renal cancer, confirmed by previous biopsy, were treated treatment of renal tumors.
with percutaneous microwave ablation. Under ultrasound
guidance, with local anesthesia, 13 G antenna, with a Erdeljan et al: Thermal ablation of small renal masses:
radiating section lenght of 3.7 cm, was placed inside the intermediate outcomes from a Canadian center. Can J Urol
tumor. Applications of MW ablation at 45 Watt for 10 18(5): 5903-5907, 2011.
minutes through one antenna were used. The therapeutic Thomas AA and Campbell SC: Small renal masses: toward
effectiveness was evaluated with a control TC and biopsy 6 more rational treatment. Cleve Clin J Med 78(8): 539-547,
months after the surgery and with the next regular uro- 2011.
oncological follow-up. Results: The median diameter of
tumors treated was 3 cm (range 2.5-6), the follow-up of 18
months (range 2-26 months) and the mean age 76 years 153
(range (65-82). The mean operative time was 10 minutes and PREDICTING PROSTATE BIOPSY
in 8/12 patients one cycle of thermal ablation was performed. OUTCOME: PROSTATE HEALTH INDEX
In 4/12 patients 2 cycles were performed. All operations (PHI) AND PROSTATE CANCER ANTIGEN
were performed under local anesthesia without significant 3 (PCA3) ARE USEFUL BIOMARKERS
complications. 9/12 patients underwent CT scan at 6 months
Matteo Ferro1, Vittorino Montanaro1,
and in 2/9 cases of persistent doubt, active neoplastic tissue
Mariano Marsicano1, Marco Capece1,
was found. The patients were subjected to post-treatment
Daniela Terracciano2, Alessandra Sorrentino2,
rebiopsy that in no case showed absence tumor tissue. At
Ada Marino2, Giuseppe Quarto3,
follow-up 10 patients are currently alive and disease free, 1
Renato De Domenico3, Domenico Sorrentino3,
patient died from other causes, 1 patient died 5 months after
Vincenzo Altieri4, Sisto Perdonà3
treatment from progressive disease (patient already
metastatic at diagnosis). Discussion: Our results, albeit with 1Urologia, Università degli Studi Federico II, Napoli;
a small group of patients and a limited follow-up, show the 2Patologia Clinica, Università Federico II, Napoli;

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

3Urologia Istituto Nazionale Tumori IRCCS “Fondazione G. the value of PCA3 for a first-line diagnostic test. Eur Urol
Pascale”, Napoli; 58(4): 475-481, 2010.
4Urologia, [Link] D’Aragona-Salerno, Italy 3 Jansen FH, van Schaik RH, Kurstjens J, Horninger W,
Klocker H, Bektic J, Wildhagen MF, Roobol MJ, Bangma
Background: The indication for first biopsy is actually based CH and Bartsch G: Prostate-specific antigen (PSA) isoform
on prostate specific antigen (PSA) serum level and digital- p2PSA in combination with total PSA and free PSA
rectal examination (DRE). These tools remained the improves diagnostic accuracy in prostate cancer detection.
cornerstones in diagnosis of prostate cancer (PCa), despite Eur Urol 57(6): 921-927, 2010.
their low predictive values. Several new markers have been
proposed to improve cancer detection. Recently phi and
PCA3 have been demonstrated as good indicators of biopsy 154
outcome. The aim of this study was to compare the ability of VALUE OF LONGITUDINAL PERCENT FREE PSA
phi and PCA3 in predicting biopsy outcome. Patients and
Luigi Benecchi1, Michele Potenzoni2, Anna Maria Pieri2,
Methods: Two hundred and fifty men were referred to our
Carmelo Destro Pastizzaro2, Matteo Quarta3,
prostate clinic to undergo their first prostate biopsy. Among
Laura Perucchini3, Mario Tonghini3,
these, 151 met inclusion criteria: age over 50 years, no prior
Fabrizio Russo3, Carlo Del Boca3
prostate surgery and biopsy, no bacterial acute or chronic
prostatitis, no use of 5-α reductase inhibitors in the previous 1Division of Urology, Cremona Hospital, Cremona;
six months, PSA values between 2 and 20 ng/ml, negative 2Division of Urology-1, Fidenza Hospital, Parma;
digital rectal examination (DRE), availability of serum and 3Division of Urology-1, Cremona Hospital, Cremona, Italy

urine samples and corresponding clinical data. PSA molecular

forms, phi index (Beckman coulter immunoassay), PCA3 Introduction and Objectives: There are limited data on the
score (Progensa PCA3 assay) and other established predictive value of longitudinal percent free PSA
biomarkers (tPSA, fPSA and %fPSA) were assessed before measurements for subsequent prostate cancer detection. To
patients underwent a 18-core prostate biopsy. Results: Values evaluate the clinical importance of percent free PSA kinetics
of %p2PSA and phi were significantly higher in patients with before 12 core prostate biopsy, we compared longitudinal
PCa compared with PCa-negative group (median values: 1.86 percent free PSA in prostate cancer patients and in controls.
vs. 1.45 and 53.38 vs. 36.21 respectively, p<0.001) and also Methods: A prospective, institutional review board approved
compared with HGPIN/ASAP (1.86 vs. 1.64 and 53.38 vs. database of 2208 12 core prostate biopsy, performed at our
36.82 respectively, p<0.001). PCA3 score values were institution from February 2002 to January 2009, was
significantly higher in PCa compared with no PCa (57 vs. 28, searched for patients with 4 or more total and free PSA done
p<0.001) and in HGPIN/ASAP vs. no PCa (54.5 vs. 28, in 1 or more years before biopsy. The percentage of freePSA
p<0.001); Figure 1. ROC curve analysis showed that slope was calculated with linear regression analysis. Results:
%p2PSA, phi and PCA3 are good indicators of malignancy 256 men entered the study. A total of 79 cancers (30.8%)
(AUCs=0.73, 0.77 and 0.71, respectively). Values of PSA, were found at the ultrasound guided prostate biopsies. The
p2PSA, %p2PSA, phi and PCA3 were significantly higher median PSA before the biopsy was 7.05 (range 1.4 to 52.7
and %fPSA significantly lower in patients with Gleason score micro/L, median age was 62 years (range 36 to 84). Median
≥7. Conclusion: %p2PSA, phi and PCA3 carry a comparable percent free PSA was 16.67% (range 1.48 to 50.7). Median
ability to predict a diagnosis of PCa in men undergoing their PSA density was 0.14 (range 0.03 to 0.99). Median PSADT
first prostate biopsy. PCA3 score is more useful in was 4.49 (range -2101 to 554). Median percent free PSA
discriminating between HGPIN/ASAP and non-cancer. slope was –0.45 for prostate cancer patients and 0.28 for
%p2PSA, phi and PCA3 also show a comparable ability to controls (p<0.001). On univariate and multivariate analysis
predict a diagnosis of high-grade PCa. percent free PSA, lnPSA slope and percent free PSA slope
showed a significant ability to predict the outcome of a 12 -
1 Marks LS, Fradet Y, Deras IL, Blase A, Mathis J, Aubin SM, cores prostate biopsy. At ROC analysis the area under the
Cancio AT, Desaulniers M, Ellis WJ, Rittenhouse H and curve (AUC) of PSA was 0.555 (95% confidence interval
Groskopf J: PCA3 molecular urine assay for prostate cancer 0.492 to 0.617) and the AUC of percent free PSA slope was
in men undergoing repeat biopsy. Urology 69(3): 532-535, 0.659 (95% confidence interval 0.597 to 0.717) with a
2007. significant statistical difference (p=0.041). A value of
2 Roobol MJ, Schroder FH, van Leeuwen P, Wolters T, van Percent free PSA slope equal to zero corresponded to a
den Bergh RC, van Leenders GJ and Hessels D: sensitivity of 65% and a specificity of 60%. Conclusion: We
Performance of the prostate cancer antigen 3 (PCA3) gene found that percent free PSA slope was an independent
and prostate-specific antigen in prescreened men: exploring predictor of prostate cancer at 12 core prostate biopsy.

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

155 switching to radical treatment. Backward and forward MVLR

PREDICTORS OF UPGRADING/UPSIZING resulted in a two variable best fit model for endpoint “upgrading
AFTER 1-YEAR RE-BIOPSY IN MEN or upsizing” (overall p=0.02, AUC=0.63): number of negative
PARTICIPATING IN A PROSPECTIVE cores>5 (protective factor, OR=0.43, p=0.19) and prostate
ACTIVE SURVEILLANCE PROGRAM volume>60cc (protective factor, OR=0.27, p=0.04). When
upgrading (27/255 pts) was considered separately, a four-
Maria Francesca Alvisi1, Tiziana Rancati2,
variable best fit model was determined (overall p=0.018,
Maurizio Colecchia3, Roberto Salvioni4, Sergio Villa5,
AUC=0.71): age>60yrs (OR=3.4, p=0.12), PSA density
Nice Bedini5, Nicola Nicolai4, Cristina Marenghi2,
(continuous variable, OR=1.04, p=0.16), number of negative
Barbara Avuzzi2, Biagio Paolini3, Tiziana Magnani2,
cores at diagnosis (protective factor, discrete variable, OR=1.07,
Silvia Catania2, Riccardo Valdagni6
p=0.19) and prostate volume>60cc (protective factor, OR=0.17,
1Prostate Cancer Program, Fondazione IRCCS Istituto p=0.1) Taking upsizing (18/255 pts) as the endpoint, MLVR
Nazionale dei Tumori, Milano; resulted in a five-variable model (overall p=0.03, AUC=0.73)
2Programma Prostata, Fondazione IRCCS Istituto Nazionale including: DRE (T2a vs. T1c, OR=3.03, p=0.16), : number of
dei Tumori, Milano; negative cores>5 (protective factor, OR=0.32, p=0.30), total
3Anatomia e Citoistologia Patologica, Fondazione IRCCS number of cores at 1-yr re-biopsy (discrete variable, OR=1.14,
Istituto Nazionale dei Tumori, Milano; p=0.18), age>60yrs (OR=0.48, p=0.23) and max core length
4Urologia Fondazione IRCCS Istituto Nazionale dei Tumori, containing cancer>10% (OR=3.4, p=0.03). Conclusion: The
Milano; present analysis suggests that upgrading and upsizing at 1-yr re-
5Radioterapia Oncologica 1, Fondazione IRCCS Istituto biopsy are independent events which are correlated to different
Nazionale dei Tumori, Milano; patient’s characteristics. Summarizing, upsizing is strongly
6Programma Prostata, Radioterapia Oncologica 1, related to “volume” variables (DRE, max core length containing
Fondazione IRCCS, Istituto Nazionale dei Tumori, Milano, cancer and number of negative cores which is a surrogate for
Italy millimeters of non-cancer) while upgrading is more related to
PSA density and number of negative cores. Age has an opposite
Introduction: Since 2005, we have been proposing active effect on the two endpoints (protective for upsizing and risk
surveillance (AS) in low-risk prostate cancer (PCa). AS factor for upgrading). Other variables are included for both
protocols include repeat biopsy at pre-defined follow-up endpoints which are a sort of surrogate for adequacy of biopsy
intervals. We here consider the outcome of the first re-biopsy (1 sampling. Supported by Fondazione Monzino
yr after AS beginning) and analyse its possible correlation with
diagnosis variables. Methods: AS institutional protocol (SAINT)
started in March 2005 and was accepted by 121 pts. Entry 156
criteria were: iPSA≤10ng/ml, Tstage≤T2a, GPS≤3+3, positive MODEL TO BIOPSY ONLY SIGNIFICANT
biopsy-cores≤20%, max core length containing cancer≤50%. PROSTATE CANCER
Pts drop out was: PSADT≤3yrs, PSA>10ng/ml,
Luigi Benecchi1, Laura Perucchini1, Matteo Quarta1,
upgrading/upsizing at re-biopsy or personal choice. In
Fabrizio Russo1, Mario Tonghini1, Anna Maria Pieri2,
November 2007 PRIAS protocol was embraced: 222 pts were
Carmelo Destro Pastizzaro2, Michele Potenzoni2,
enrolled (February 2012). PRIAS vs. SAINT differs on:
Carlo Del Boca1
maximum 2 positive cores and PSA density<0.2ng/ml/cc. Age,
iPSA, PSA density, number of positive cores, % of positive 1Division of Urology, Cremona Hospital, Cremona;
cores, max core length containing cancer, average core length 2Division of Urology, Fidenza Hospital, Parma, Italy
containing cancer, number of negative cores at diagnosis, total
number of cores at diagnosis, total number of cores at 1yr- Introduction: Many patients diagnosed with low grade prostate
rebiopsy, prostate volume, PCa histology and DRE were cancer may have indolent disease that may not benefit from
considered as factors potentially influencing upgrading/ immediate therapy. Our objective was to create a nomogram
upsizing. GPS was not considered (all pts had GPS=3+3). Three using PSA kinetics to predict high-grade prostate cancer
separate endpoints were considered: (1) upgrading OR upsizing; (Gleason sum of 7 or more) (HG PCa). Materials and
(2) upgrading and (3) upsizing. Multivariable logistic regression Methods: From a prospective database of twelve core prostate
(MVLR) was used to analyze correlations between variables biopsies, we identified 630 men with at least 3 consecutive
and endpoints at first re-biopsy. Results: Statistical analysis was PSA measurements over a 2 year interval prior to biopsy.
performed on 255 pts with complete records (1 yr min f-up). Least squares regression was used to calculate “PSA
40% pts had a negative 1-yr biopsy (0 positive cores), acceleration” (logPSA slope). Logistic regression was then
45/255(17.7%) pts had upgrading/upsizing after re-biopsy, used to predict HG PCa at biopsy using age, digital rectal

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

Figure 1 (abstract 156).

examination findings (DRE), PSA, free to total PSA ratio Luigi Benecchi1, Matteo Quarta1, Laura Perucchini1,
(%fPSA), prostate volume and PSA acceleration. The Mario Tonghini1, Fabrizio Russo1,
population was randomly divided into two groups. A Carmelo Destro Pastizzaro2, Anna Maria Pieri2,
nomogram was developed in the training set and was then Michele Potenzoni2, Carlo Del Boca1
evaluated in the validation cohort. Results: Of the 630 men,
189 (30%) were diagnosed with prostate cancer on biopsy, and 1Division Of Urology Cremona Hospital, Cremona;
75 (11.9%) had HG PCa. We applied backwards variable 2Division Of Urology Fidenza Hospital, Parma, Italy
elimination to the full model, with the intent of identifying the
most parsimonious and accurate model. In this model, all Introduction: Several studies have demonstrated a significant
variables except age and PSA were significant predictors of association between PSA kinetics and clinically significant
HG PCa, and were included in the nomogram (Figure 1). In prostate cancer. Thus, the aim of the current study was to
the validation population, the nomogram based on the develop a model to predict high-grade prostate cancer (HG
parsimonious model had superior discrimination (AUC=0.817) PCa) on repeated prostate biopsy, incorporating “PSA
compared to PSA, %fPSA, PSA density or PSA acceleration acceleration”. Materials and Methods: A logistic regression
alone. Using a cutpoint of 17, the nomogram had a sensitivity model was constructed to predict HGPCa (Gleason score 7 or
of 85.7% and specificity of 69.3% for HGPCa. Conclusion: more) at repeated biopsy, using age, family history, digital
The identification of clinically significant prostate cancer is rectal examination findings (DRE), PSA, percent free PSA
essential to avoid overdiagnosis. We successfully developed a (%fPSA), PSA density and PSA acceleration from 362 men,
model to predict HG PCa including %fPSA, DRE findings, who underwent a repeated prostate biopsy with at least 3 prior
prostate volume and “PSA acceleration”. Although the PSA measurements from which to calculate “PSA
nomogram performed well in the internal validation, acceleration”. Results: On repeated biopsy, 105 (29%) men
additional studies are warranted in external populations to were diagnosed with prostate cancer, of which 45 (13%) had
confirm the clinical utility of this predictive tool. a Gleason sum of 7 or more. In the backward stepwise logistic
regression model, %fPSA, DRE, family history, PSA density
and PSA acceleration provided the most parsimonious model
157 to predict HGPCa after a negative initial biopsy, and were
HOW TO REBIOPSY ONLY MEN WITH included in the nomogram. The nomogram was well-calibrated
HIGH GRADE PROSTATE CANCER, and had an area under the ROC curve of 0.774, which
AFTER A PREVIOUS NEGATIVE BIOPSY exceeded that of any single risk factor. Conclusion: We

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

Figure 1 (abstract 158).

successfully developed a model to predict HGPCa on repeat respect to lbr and linc. G1 lrb was defined as lrb less than 2
prostate biopsy including %fPSA, DRE findings, family times/week, G2 if lrb more than twice/week, G3 if daily lrb
history, PSA density and “PSA acceleration”. was present or if any number of blood transfusion and/or laser
coagulation was necessary. G1 linc was scored if unintentional
stool discharge was “sometimes” experienced, G2 linc if
158 unintentional stool discharge was “often” experienced or if pts
RECTAL TOXICITY 7 YEARS AFTER HIGH-DOSE sporadically used sanitary pads; G3 if pts reported daily
RADIATION FOR PROSTATE CANCER: CLINICAL unintentional stool discharge or use of sanitary pad >2
AND DOSIMETRIC PREDICTORS times/week. The correlation between pre-treatment
morbidities, hormonal therapy, drug prescription, presence of
Tiziana Rancati1, Gianni Fellin2, Claudio Fiorino3,
diabetes or hypertension, abdominal surgery prior to RT,
Vittorio Vavassori4, Emanuela Cagna5, Giuseppe Girelli6,
presence of RTOG greater than 1 toxicity, presence of G2-G3
Flora A. Mauro7, Pietro Gabriele8, Riccardo Valdagni9
acute fecal incontinence, pelvic nodes and seminal vesicles
1ProstateCancer Program, Fondazione IRCCS Istituto irradiation, mean rectal dose, dose-volume histograms
Nazionale dei Tumori, Milano; constraints (from V20Gy to V75Gy) and lrb/linc was
2Radioterapia Oncologica, Ospedale Santa Chiara; investigated by uni- and multivariate (MVA) logistic analyses.
3Fisica Medica, Istituto Scientifico San Raffaele; 347/515 pts had at least 3 toxicity questionnaires in the first
4Radioterapia Oncologica, Humanitas - Gavazzeni, 36 mos after the end of RT. Correlation between the mean
5Radioterapia Oncologica, Ospedale Sant’Anna; score of fecal incontinence in the first 36 mos and linc at 7 yrs
6Radioterapia Oncologica, Ospedale ASL 9 Di Ivrea, was also investigated. Results: 32/515 G1, 2/515 G2 and 3/515
7Radioterapia Oncologica, Villa Maria Cecilia; G3 lrb were registered. 50/515 G1, 3/515 G2 and 3/515 G3
8Radioterapia Oncologica, IRCCS Di Candiolo; linc were reported. Lrb was only correlated to V75Gy
9Programma Prostata, Radioterapia Oncologica 1, (continuous variable): p=0.02, OR=1.07. The prevalence of
Fondazione IRCCS, Istituto Nazionale dei Tumori, Milano, lrb≥1 at 7 yrs was significantly correlated with incidence of
Italy G2-G3 lrb in the first 3 yrs after RT treatment: 42.3% in pts
with G2-G3 bleeding in the first 3 yrs vs. 5.6% in non-lrb pts
Purpose: To evaluate long term prevalence of late rectal (p<0.0001, chi-squared). Linc was correlated to multiple
bleeding (lrb) and of late fecal incontinence (linc) after high- variables. In MVA (overall p<0.0001, AUC=0-77) V40Gy
dose radiotherapy (RT) in prostate cancer patients (pts) (continuous variable, p=0.09, OR=1.015), use of
accrued in AIROPROS 0102 trial (RT doses: 70-80Gy, 1.8- antihypertensives (protective factors, p=0.005, OR=0.38),
2Gy/fr) and to model the relationship between lrb/linc and presence of abdominal surgery before RT (p=0.004, OR=4.7),
clinical/dosimetric factors. Patients and Methods: Self- presence of haemorrhoids (p=0.008, OR=2.6) and presence of
reported questionnaires of 515 pts with a minimum follow-up G2-G3 acute incontinence (p=0.007, OR=4.4) resulted to be
of 6 yrs (median follow-up 7 years) were analyzed with correlated to linc. The figure shows the nomogram which was

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

developed starting from MVA results. Linc at 7 yrs was also incontinence following high-dose prostate cancer radiotherapy
correlated to the mean incontinence scores in the first 36 mos (RT). To this aim, a new longitudinal score of incontinence
(p<0.0001): pts without linc at 7 yrs had a mean score of 0.1 (i.e., the mean late incontinence score) was introduced starting
during the first 36 mos, while pts with G1 and with G2-G3 from the four-grade scale adopted for the AIROPROS
linc at 7 yrs had a mean score of 0.5 and 0.78 during the first (prostate working group of the Italian Association of Radiation
36 mos, respectively. The prevalence of linc≥1 at 7 yrs was Oncology) 0102 trial. Materials and Methods: AIROPROS
significantly correlated with the mean incontinence scores in 0102 trial information 586 men recruited in the AIROPROS
the first 3 yrs after RT treatment: 37.3% in pts with mean 0102 trial, which included the prospective evaluation of acute
score ≥0.5 vs. 10% in pts with mean score <0.5 (p<0.0001, and late faecal incontinence through self-assessed
chi-squared). Conclusion: A fraction of pts is still experiencing questionnaires, were analyzed. Incontinence was scored as
rectal toxicity symptoms 7 yrs after RT: 7.2% lrb and 10.9% follows: Grade 1, unintentional stool discharge “sometimes”
linc. Prevalence of toxicity at 7 yrs is significantly correlated experienced; Grade 2, unintentional stool discharge “often”
to incidence in the first 3 yrs after RT treatment. This is an experienced or sporadically use of sanitary pads; and Grade 3,
indication of a chronic occurrence of symptoms, with late daily unintentional stool discharge or use of sanitary pads >2
fecal incontinence playing the major role. Mean score for times/week reported. For the present analysis, a new
incontinence during the first 36 mos after RT can be used as a longitudinal definition of late faecal incontinence expressed as
surrogate endpoint for late (>6yrs) fecal incontinence. A the average score of late incontinence using the four-grade
nomogram for linc prediction at 7 yrs was developed. Linc is scale was considered. Information was recorded on co-
correlated to clinical and dosimetric risk factors and morbidity (with particular attention to hypertension,
individualised toxicity prediction can be performed through cardiovascular history, diabetes mellitus, auto-immune
the proposed nomogram. diseases), previous abdominal surgery (rectum-sigma
resection, kidney resection, cholecystectomy, appendectomy),
and use of drugs (anticoagulants or antiaggregants,
159 antihypertensives, hypoglycaemic or insulin). Rectal dose-
PREDICTING LATE FAECAL INCONTINENCE volume histograms of the whole treatment were recorded for
AFTER HIGH-DOSE RADIOTHERAPY all patients and the percent volume of rectum receiving more
FOR PROSTATE CANCER: APPLICATION than 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, 70 Gy (named
OF ARTIFICIAL NEURAL NETWORK V20Gy¡V70Gy) were considered. ANN analysis: The overall
CLASSIFICATION ON A NEW population was split into a train and a test set. The train group
LONGITUDINAL DEFINITION was used to optimize the inner weights and biases of the ANN
by means of back propagation and conjugated gradients
Mauro Carrara1, Stefano Tomatis2, Tiziana Rancati3,
training algorithms. To avoid data over fitting, the number of
Claudio Fiorino4, Vittorio Vavassori5, Gianni Fellin6,
inputs and hidden neurons in the ANN was limited and the
Emanuela Cagna7, Francesca Tortoreto8,
training iterative process was stopped after a predetermined
Giuseppe Girelli9, Riccardo Valdagni10
number of epochs was reached. The test set was used as an
1Medical Physics, Fondazione IRCCS Istituto Nazionale dei independent set to verify the generalization capabilities of the
Tumori, Milano; model. A value of longitudinal late faecal incontinence equal
2Fisica Medica, Fondazione IRCCS Istituto Nazionale dei or greater than one was arbitrarily considered as the endpoint,
Tumori, Milano; because this score selected those patients with persistent
3Programma Prostata, Fondazione IRCCS Istituto Nazionale symptoms. Results: Of the 586 patients, 36 had an
dei Tumori, Milano; incontinence score greater than 0 on the baseline pre-treatment
4Fisica Medica Istituto Scientifico San Raffaele, Milano; questionnaire and were excluded from the analysis. Thus, the
5Radioterapia Oncologica, Humanitas, Gavazzeni, Bergamo; number of patients available for the analysis was 550 (22
6Radioterapia Oncologica, Ospedale Santa Chiara, Trento; positive cases), which were split in 366 (15 positive) and 184
7Radioterapia Oncologica, Ospedale Villa Maria Cecilia; (7 positive) cases for train and test set, respectively. Among
8Radioterapia Oncologica, Ospedale Isola Tiberina, Roma; the previously described large amount of possible ANN input
9Radioterapia Oncologica, Ospedal ASL 9 Di Ivrea; data, a suitable subset of variables able to better predict late
10Programma Prostata, Radioterapia Oncologica 1, faecal incontinence was selected. Five variables were
Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, identified, i.e. the V40Gy (continuous variable), surgery
Italy (yes/no), seminal vesicles irradiation (yes/no), use of
anticoagulants (yes/no), and presence of haemorrhoids
Objectives: To study the application of artificial neural (yes/no). The resulting ANN classifier (4 hidden neurons) was
network (ANN) classification for the prediction of late faecal able to correctly predict late faecal incontinence with

1945
 ANTICANCER RESEARCH 32: 1843-1966 (2012)

sensitivity and specificity values of 80% and 68%, respectively 5Urologia, Università Magna Graecia di Catanzaro;
for the overall population. Following ROC analysis, area under 6Urologia, [Link] D’Aragona, Salerno;
the ROC curve was 0.84. Adding the acute incontinence 7Urologia, Ospedale S. Maria Delle Grazie, Pozzuoli (NA);

information as a further ANN input variable, sensitivity and 8Urologia Seconda, Università degli Studi di Napoli;

specificity increased to 80% and 95%, respectively. Following 9Urologia, Istituto Nazionale Tumori IRCCS “Fondazione G.

ROC analysis, area under the ROC curve increased to 0.92. Pascale”, Napoli;
10Urologia Università degli Studi di Salerno, Italy

Introduction: Acute radiation cystitis (RC) is a common and

debilitating problem in patients undergoing radiotherapy for
urogenital malignancies. Acute RC symptoms include painful
micturition, urgency, frequency, and nicturia We studied the
feasibility and efficacy of intravesical instillations with Ialuril®
(sodium hyaluronate and chondroitin sulfate sterile solution)
to reduce acute radiation cystitis in men and women
undergoing pelvic radiotherapy. Materials and Methods: The
single-arm study was performed between September 2010 and
June 2011 and included 15 patients who met the following
criteria: primary or adjuvant radiotherapy for pelvic cancer.
Exclusion criteria were: bladder cancer, LUTS, overactive
bladder syndrome. Symptoms of haematuria, frequency of
voiding and the visual analogue scale of pelvic pain (range 0-
10) were evaluated before and after the treatment with follow-
Figure 1. ROC curves for late faecal incontinence classification with up of 6 months. During radiotherapy, all patients received
ANN. Results were obtained omitting and including the acute weekly bladder instillations of 50 ml of sterile sodium HA
incontinence information as input to the ANN.
1.6% and CS 2.0% solution (IALURIL®). Results: A
reduction of degree symptoms of haematuria occurred in 13
Conclusion: ANN analysis combined to the selection of of 15 patients (p<0.001). reduction of frequency of voiding
significant input variables and a longitudinal definition of and of visual analogue scale score were significantly lower
faecal incontinence resulted to be a powerful tool to predict than baseline at the 6-months (p<0.001, p 0.002, respectively).
late rectal morbidity in patients treated for prostate cancer. Discussion and Conclusion: Bladder instillations with Ialuril®
Models like the one described in this study might help seems to reduce acute post-irradiation cystitis symptoms in
radiation oncologists to predict and possibly avoid an patients treated for pelvic malignancies. Further studies are
unnecessary worsening of quality of life of a single patient, needed to obtain more robust evidence.
introducing treatment’s corrections to better tailor the
treatment to patient’s characteristics. 1 Maduro JH, Pras E, Willemse PH and de Vries EG: Acute
and long-term toxicity following radiotherapy alone or in
combination with chemotherapy for locally advanced
160 cervical cancer. Cancer Treat Rev 29(6): 471-488, 2003.
PROPHYLACTIC BLADDER INSTILLATIONS WITH 2 Butrick CW: Radiation cystitis. In: Howard FM, Perry CP,
IALURIL® MAY REDUCE SYMPTOMS OF ACUTE Carter JE, El-Minawi AM (eds.). Pelvic pain: diagnosis and
RADIATION CYSTITIS IN PATIENTS UNDERGOING management, 1st edn. Williams and Wilkins, Baltimore,
RADIOTHERAPY FOR PELVIC TUMOURS 2000.
3 Pavlidakey PG and MacLennan GT: Radiation cystitis. J
Matteo Ferro1, Roberto Sanseverino2, Giorgio Napodano2,
Urol 182(3): 1172-1173, 2009.
Vincenzo Serretta3, Pierluigi Bove4, Rocco Damiano5,
Umberto Greco6, Giovanni Di Lauro7, Marco De Sio8,
Sisto Perdonà9, Vincenzo Altieri10
161
1Urologia, Università Degli Studi Federico II, Napoli; CENTRALIZED REVISION OF DIAGNOSTIC
2Urologia, Ospedale Umberto I, Nocera Inferiore; PATHOLOGIC SLIDES FOR PROSTATE CANCER
3Urologia, Dipartimento Materno-Infantile, Andrologia e PATIENTS ON ACTIVE SURVEILLANCE: IS IT JUST
Urologia, Università Di Palermo; TIME AND RESOURCE CONSUMING OR DO WE
4Urologia, Università Tor Vergata, Roma; REALLY NEED IT?

1946
 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

Maurizio Colecchia1, Maria Francesca Alvisi2, differences were observed in 30/248 (12.1%): 20/30 (66.7%)
Biagio Paolini3, Nicola Nicolai4, Sergio Villa5, changes were related to upgrading (18 to GPS=3+4, 1 to
Roberto Salvioni4, Cristina Marenghi2, GPS=4+3 and 1 to GPS=4+4). 10/30 (33.3%) pts had an
Tiziana Rancati2, Riccardo Valdagni6 upsizing: 1 SAINT pt exceeded 20% of positive cores, 5
SAINT pts exceeded 50% of max tumor length of positive
1AnatomoPathology, Fondazione IRCCS Istituto Nazionale cores, while 4 PRIAS pts increased from 2 to 3 or 4 positive
dei Tumori, Milano; cores. Among significant differences, there were 20 changes
2Programma Prostata Fondazione IRCCS Istituto Nazionale (8.1% of total revisions) that led to an upgrading of the pt’s
dei Tumori, Milano; risk class (19/20 moved from Low-Risk to Intermediate-Risk
3Anatomia e Citoistologia Patologica, Fondazione IRCCS and 1/20 from Low-Risk to High-Risk class). Conclusion:
Istituto Nazionale Dei Tumori, Milano; Central pathology review reduces population heterogeneity in
4Urologia Fondazione, IRCCS, Istituto Nazionale dei the specific setting of AS programs. Significant reclassification
Tumori, Milano; of risk category involved 12% of pts. Current clinical
5Radioterapia Oncologica 1, Fondazione IRCCS Istituto consequences of central review cannot be determined.
Nazionale Dei Tumori, Milano;
6Programma Prostata, Radioterapia Oncologica 1,

Fondazione IRCCS Istituto Nazionale Dei Tumori, Milano, 162

Italy USE OF ICIQ QUESTIONNAIRE FOR
THE EVALUATION OF PELVIC FLOOR
Introduction and Objectives: Active Surveillance (AS) is MUSCLE TRAINING AFTER RADICAL
offered to prostate cancer (PCa) patients (pts) with very low PROSTATECTOMY OR CYSTECTOMY
risk disease, with well defined diagnostic biopsy details WITH BLADDER RECONSTRUCTION
coupled to clinical stage criteria and PSA≤10 ng/ml. For this
Mariateresa Carchedi, Anna Palazzetti, Andrea Buffardi,
reason, in order to standardize diagnostic inclusion criteria, we
Fabio Bonfanti, Antonino Battaglia, Francesco Travaglini,
requested pathologic review before AS enrollment. We here
Ettore Dalmasso, Marco Allasia, Beatrice Lillaz,
report on second opinion of prostate needle biopsies to
Paolo Destefanis, Dario Fontana
determine how often the expert opinion of a uro-pathologist
resulted in a different diagnosis, in the group of pts who were SC Urologia 2, AOU San Giovanni Battista Molinette,
proposed for AS. Patients and Methods: AS institutional Torino, Italy
protocol (SAINT) started in March 2005. Entry criteria were:
initial PSA≤10 ng/ml, Tstage≤T2a, GPS≤3+3, positive biopsy- Background: Perioperative and postoperative pelvic floor
cores≤20%, max core length containing cancer≤50%. In muscle training have shown to hasten the recovery of urinary
November 2007 PRIAS protocol was embraced. PRIAS vs. continence after radical prostatectomy. Even if pelvic floor
SAINT differs on: maximum 2 positive cores and PSA muscle training is recommended by EAU guidelines and is
density<0.2 ng/ml/cc. From October 2005 through July 2010, widespread used, this treatment has not yet been standardized.
a second opinion on biopsy diagnosis was requested in 248 In the present study we evaluated the use of three ICIQ
cases, due to outside diagnosis. We analyzed differences questionnaires on a population of prostate and bladder cancer
between outside diagnosis and institutional expert opinion. For patients undergoing pelvic floor muscle training in order to
this purpose we considered two different classes of check the improvement of urinary continence and other
differences: minor differences (changes which did not prevent symptoms during this treatment. Patients and Methods:
AS enrollment) and significant changes (differences which Between September 2010 and August 2011, all patients
resulted in a change in prognosis and closed the possibility of referring to pelvic floor physiokinesiotherapy ambulatory of
AS enrollment). Results: Overall 40/248 (16.1%) cases had our department were proposed to fill-in the International
minor differences (18 referred to SAINT pts and 22 to PRIAS Consultation on Incontinence Questionnaire-Urinary
pts). In the SAINT group, 12/18 (66.7%) biopsies were Incontinence Short Form (ICIQ-UI ShortForm) and the
increased in the max core length containing cancer (but International Consultation on Incontinence Questionnaire
still≤50%) and 6/18 (33.3%) had a change in the number of Urinary Incontinence Quality of Life Module (ICIQLUTSqol).
positive cores (3 reductions and 3 increases, but still≤20% of All male patients were also required to fill-in International
total cores). In the PRIAS group 10/22 (45.5%) changes were Consultation on Incontinence Questionnaire Male Sexual
related to upsizing (from 1 to 2 positive cores) and 5/12 Matters Associated with Lower Urinary Tract Symptoms
(22.7%) to downsizing (from 2 to 1 positive core). 7/22 Module (ICIQMLUTSsex). All patients were waiting for a
(31.8%) changes were related to differences in core length major pelvic surgical procedure (radical prostatectomy or
containing cancer (from below to above 50%). Significant radical cystectomy plus bladder reconstruction). Questionnaires

1947
 ANTICANCER RESEARCH 32: 1843-1966 (2012)

were administered before surgery, after catheter removal, and 3, Massimo Maffezzini6, Giuseppe Carrieri7,
6, 9 and 12 months after surgery. All patients received multiple Giuseppe Morgia8, Dario Fontana1
supervised pelvic floor training session from a dedicated nurse
before surgery and immediately after catheter removal and 1SC Urologia 2, AOU San Giovanni Battista Molinette,
repeated for some weeks, and oral and written instructions on Torino;
pelvic floor muscle contractions and a structured programme 2Urologia AO San Lazzaro, Alba, CN;

of exercises to be performed at home while lying, sitting and 3Urologia, Ospedale degli Infermi di Rivoli, Rivalta, TO;

standing. Data about erectile dysfunction treatment were also 4Urologia, AOU S. Maria della Misericordia Udine, Udine

collected. Results: A total of 43 patients agreed to fill-in the 5Urologia, AOU Maggiore della Carità, Novara;

questionnaires. 33 patients underwent traditional retropubic 6Urologia, Ospedali Galliera, Genova;

radical prostatectomy, 6 a robotic-assisted radical 7Urologia, Ospedali Riuniti Foggia;

prostatectomy and 4 a radical cystectomy with bladder 8Urologia, Policlinico G. Martino Messina, Italy

reconstruction (Y-neobladder). Among these last 4 patients, 3

were male and 1 female. Mean age was 65.42 years ± 6.26. Background: In the last 90’s, we proposed a new kind of ileal
The comparison between the questionnaires before surgery and orthotopic reservoir: the Y-neobladder proved to be easy and
after catheter removal showed a clear worsening of all fast to create, to provide good functional results and to have a
parameters in all the 3 forms (p<0.05). At 6 months very low incidence of strictures of ureteral-neobladder
questionnaires we recorded statistically significant anastomosis. In order to confirm those first results, we
improvements at most of the questions of ICIQLUTSqol (2a- conducted a retrospective multi-institutional study. Patients
8a, 10a, 16a, 16b, 18a-19a, 21) and at the whole ICIQ-UI short and Methods: Eight different Urologic Departments from 8
form (p<0.05). At 9 and 12 months questionnaires Italian hospitals provided the data of all their patients who
improvements recorded at 6 months are confirmed and some underwent radical cystectomy followed by bladder substitution
further statistically significantly improvement is recorded in with Y-neobladder. The main steps of surgical technique used
ICIQ-LUTSqol (9˚ month: 13a, 14a; 12˚ month: 8b and 10b) were previously described and published. The following
(p<0.05). As far as ICIQ-MLUTSsex for the 42 male patients parameters were recorded and retrospectively reviewed:
is concerned, no statistically significant improvement was indication for radical cystectomy, surgery notes, early and late
recorded during follow-up. Discussion and Conclusion: Pelvic complications, data about micturitions, continence and self-
floor muscle training is extensively used after radical catheterism and oncologic follow-up. Continence was defined
prostatectomy and radical cystectomy with bladder good if no use of pads was recorded, satisfactory for 1 pad,
reconstruction in order to recover an early continence. unsatisfactory >1 p pads. Statistical analysis was performed
Nevertheless, the results and the improvements are difficult to through a PC software. Results: Complete data were available
monitor during and after the treatment, and many for 227 patients, who underwent the procedure between
questionnaires have been proposed and used. International September 1999 and January 2010. The mean age at radical
Consultation on Incontinence provides many modular cystectomy was 65.12±9.08 years. Two hundred and one
questionnaires that are extensively used for various kind of patients were male, while 26 were female. The mean follow-
incontinence. The 3 questionnaires that we have evaluated up was 33.0±27.34 months. The indication to radical
proved to be effective and easy to use in this context, especially cystectomy was given for muscle-invasive bladder cancer in
for ICIQ-UI short form. 64% of patients, recurrent non-responsive superficial bladder
cancer in 34%, other pelvic cancer in 1% and benign bladder
Abrams P, Avery K, Gardener N and Donovan J: ICIQ diseases in 1%. As far as functional outcome are concerned,
Advisory Board. The International Consultation on the mean daytime voiding frequency was 5.83 micturitions,
Incontinence Modular Questionnaire: [Link]. J Urol while the mean nighttime voiding frequency was 2.47
175(3 Pt 1): 1063-1066, 2006. micturitions. A good or satisfactory daytime continence was
obtained in 85% of patients with at least 1 year of follow-up
(133/157 patients), and nighttime continence was good or
satisfactory in 76% (119/157). The following late
163
complications were recorded: stricture of urethral-neobladder
Y- NEOBLADDER: AN UPDATE OF A MULTI-
anastomosis in 7.49% of patients (17/227), stricture of
INSTITUTIONAL RETROSPECTIVE STUDY
ureteral-neobladder anastomosis in 2 patients (2/445 renal
Paolo Destefanis1, Andrea Bosio1, Alessandro Bisconti1, units, 0.45%), neobladder stone in 13 patients (5.73%), urinary
Mariateresa Carchedi1, Giuseppe Fasolis2, sepsis in 11 (4.85%), vaginalneobladder fistula in 3 out of 27
Maurizio Bellina3, Mauro Mari3, Simone Crivellaro4, female patients (11%). No severe metabolic complication was
Bruno Frea4, Giansilvio Marchioro5, Carlo Terrone5, recorded. Conclusion: Even though these data are

1948
 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

retrospectively collected, on several different hospitals and of ropivacain 400 mg 5Ml/h and intravenous 0.9% saline
with irregular follow-up, the results of the study suggest that solution released by elastomeric pump. Each patient
the Y-neobladder provide good functional outcomes with a low underwent total intravenous anesthesia, was instructed to use a
rate of late complications. We underline that the incidence of patient controlled analgesic device (PCA Midial pump 586).
strictures of ureteral-neobladder anastomosis is extremely low Outcome measured over 72h were visual analogue scale,
(0.45% of renal units) if compared to the results of other ileal simple scale and adverse effects. Results: Results are summed
reservoirs. in the follow Tables I and II:

1 Fontana D, Bellina M, Fasolis G, Frea B, Scarpa RM, Mari

M, Rolle L and Destefanis P: Y-neobladder: an easy, fast,
Table I
and reliable procedure. Urology 63(4): 699-703, 2004.
2 Destefanis P, Bosio A, Carchedi M, Negro C, Fasolis G, Group Patients Pain VAS PCA Morphine
Bellina M, Mari M, Frea B, Terrone C, Maffezzini M,
Carrieri G, Morgia G and Fontana DY: Neobladder: an A 13 (26%) Severe 7/8 5/6 h 7 mg
italian multiinstitutional retrospective study. European 22 (44%) Average 4/5 6/7 h 5 mg
Urology Supplements 9(2): 150, 2010. 6 (12%) mild 1/2 24 h 0.8 mg
B 6 (12%) mild 1/2 24 h 0.8 mg

164
CONTINUOUS SUBFASCIAL WOUND Table II
INFUSION FOLLOWING RADICAL RETRO
PUBIC PROSTATECTOMY: A PROSPECTIVE, A A (%) B B(%)
RANDOMIZED INSTITUTIONAL
Drowsiness 22 44 - -
DOUBLE-BLIND STUDY
NAUSEA 20 40 - -
Domenico Sorrentino1, Alfonsa Giglio2, Vincenzo Romano2, Vomit 10 20 3 6
Giuseppe Quarto3, Renato De Domenico3, Delay C. 19 39 - -
Thrill 6 12 4 8
Dante Di Domenico4, Tronino Modestino4,
Hypotension - - - -
Marco De Sio5, Vincenzo Altieri6,
Matteo Ferro4, Sisto Perdonà3
1UOC-Urologia Istituto Nazionale Tumori, Fondazione “G. Conclusion: Continuous wounds infusion of local anaesthetics
Pascale”, Napoli; are safe and effective to reduce pain and adverse effects
2Anestesia, Istituto Nazionale Tumori, IRCCS “Fondazione related to postoperative analgesic drugs administrations.
G. Pascale”, Napoli;
3Urologia, Istituto Nazionale Tumori, IRCCS “Fondazione 1 Cheong WK, Seow-Choen F, Eu KW, Tang CL and Heah
G. Pascale”, Napoli; SM: Randomized clinical trial of local bupivacaine perfusion
4Urologia, Università Federico II, Napoli; versus parenteral morphine infusion for pain reliefafter
5Urologia Seconda, Università degli Studi di Napoli; laparotomy. Br J Surg 88(3): 357-359, 2001.
6Urologia, Università degli Studi di Salerno, Italy 2 Wu CL, Cohen SR, Richman JM, Rowlingson AJ, Courpas
GE, Cheung K, Lin EE and Liu SS: Efficacy of
Aim: To evaluate the efficacy of continuous wound infusion of postoperative patient-controlled and continuous infusion
local anaesthetic agent after open radical retro pubic epiduralanalgesia versus intravenous patient-controlled
prostatectomy (RRP). Patients and Methods: 97 patients (54- analgesia with opioids: a meta-analysis. Anesthesiology
75 year old) underwent RRP for prostate cancer and were 103(5): 1079-1088; quiz 1109-1110, 2005.
enrolled in a double –blind prospective study into two groups 3 Bilgin TE, Bozlu M, Atici S, Cayan S and Tasdelen B:
randomized (1:1) for pain control. All patients were placed Wound infiltration withbupivacaine and intramuscular
both continuous wound infusor (Painfusor Catheter -Baxter) diclofenac reduces postoperative tramadol consumption in
and a venous line connected to elastomeric pump. Group A patients undergoing radical retropubic prostatectomy:
(49 patients, main age 66,3, main incision length 74 mm) aprospective, double-blind, placebo-controlled,randomized
received intravenous morphine 12 mcg/Kg/h released by study. Urology 78(6): 1281-1285, 2011.
elastomeric pump and continuous wound infusion of 0.9% 4 White PF and Kehlet H: Improving postoperative pain
saline solution. Group B (48 patients main age 68.2, main management: what are the unresolved issues? Anesthesiology
incision length 78 mm) received continuous wound infusion 112(1): 220-225, 2010.

1949
 ANTICANCER RESEARCH 32: 1843-1966 (2012)

165 histologically diagnosed. After a two-years follow-up the

TRANSITIONAL CELL CARCINOMA patient is in good health condition, free from recurrences and
(TCC) IN RENAL TRANSPLANT PATIENTS: progression, but under dialytic treatment. Conclusion:
A 20 YEARS RETROSPECTIVE ANALYSIS Treatment of TCC in transplant patients is challenging. Tumor
often develops years after renal transplantation. In our
Andrea Bosio1, Fedele Lasaponara1, Ettore Dalmasso1,
retrospective analysis low-risk tumors had a good long-term
Paolo Destefanis1, Giovanni Pasquale1, Omidreza Sedigh1,
prognosis and pTa stage at diagnosis was highly predictive for
Eugenio Alessandria1, Silvia Santià1,
long-term survival. High-risk tumors, particularly pT1G3 in
Giuseppe Paolo Segoloni2, Dario Fontana3
our series, had on the contrary a very poor prognosis with no
1SC Urologia 2, AOU San Giovanni Battista Molinette, long-term survival despite aggressive surgical management.
Torino; Variations in immunosuppressive regimen and optimization of
2Cattedra di Nefrologia, AOU San Giovanni Battista intravescical prophylaxis should play a role in the treatment
Molinette, Torino; of the disease. Large series and meta-analysis are desirable to
3Cattedra di Urologia, AOU San Giovanni Battista Molinette, draw conclusions on this challenging issues.
Torino, Italy

Background: Transitional Cell Carcinoma (TCC) in renal 166

transplant patients is rare but aggressive. Immunosuppression SECOND-LINE TREATMENT WITH
plays a role in its pathogenesis. The best clinical and surgical SORAFENIB IN POOR-RISK ADVANCED
management of TCC in this population is unclear due to the RENAL CELL CARCINOMA: A CASE REPORT
low incidence of the disease. Aggressive surgical strategies
Donatello Gasparro1, Sara Tarasconi2
have been proposed. We report on the management of TCC in
renal transplant patients in the Transplant Centre of Torino in 1Divisione di Oncologia Medica Azienda Ospedaliero,
the last 20 years. Patients and Methods: 2581 renal transplants Universitaria di Parma;
were performed in the Transplant Center of Torino from 1981 2Pronto Soccorso/medicina D’Urgenza, Azienda

to 2011. We made a retrospective analysis of the last 20 year Ospedaliero, Universitaria Di Parma, Italy
activity. Clinical reports were reviewed looking for TCC
diagnosis, treatment and prognosis. 9 cases of TCC were Introduction: In the last few years the development of targeted
identified: 8 bladder TCC, 1 upper urinary tract TCC (in the therapies has significantly improved prognosis of patients with
graft renal pelvis). Results: 8 patients (4 males and 4 females) clear cell metastatic renal cell carcinoma (mRCC).
were diagnosed with bladder TCC. Medium time from Nevertheless, life expectancy of patients with poor-risk mRCC
transplant to diagnosis was in media 6-7 years (range from 3 remains less than one year. Case Report: We describe a case
months to 13 years). Average tumor size was 1.2 cm (0.5-2 of a 46-year-old male patient (S.C.), heavy smoker, who
cm) at diagnosis. There was no predominant location in the underwent nephrectomy at another institute on January 2006
bladder and TURB had no complications. Pathological for a histologically confirmed clear cell RCC (Fuhrman
examinations were the following: pTaG1 in 3 cases, pTaG3 in nuclear grade III). In September 2008 a CT scan (performed
1 and pT1G3 in 4 (1 associated with CIS). 2 out of 3 pTaG1 for the onset of asthenia, confusion and detectable
patients had a multifocal disease. 6 patients received hepatomegaly) showed multiple metastatic liver lesions, and a
intravescical chemioprophylaxis (5 mytomicine C, 1 biochemical evaluation showed a severe hypercalcemia. The
epirubicine). No BCG immunoprophylaxis was used. 3 out of patient was admitted to our center, his symptoms were settled
4 patients with pT1G3 TCC progressed to muscle-invasive with rehydration, diuretics and Zoledronate. A skeletal
bladder cancer: 1 had metastatic disease at pT2 diagnosis, 2 scintigraphy detected multiple bone lesions. The patient was
underwent radical cystectomy, native nephroureterectomy and judged to be at poor risk according to Motzer criteria, due to
graft urinary diversion but they both died after 1 year. All pTa his performance status (Karnofski 50%), severe anaemia, high
patients are disease-free at a 7 years (range from 4 to 10 years) corrected calcium level and high lactate dehydrogenase level.
median follow-up. 1 pT1G3 patient is disease-free at 1 year At this point, in December 2008 treatment with Temsirolimus
follow-up. Cyclosporine + azathioprine + steroid was the most was started, at a dose of 25 mg once a week. After two weeks
commonly used immunosuppressive treatment. 5 patients the patient exhibited marked clinical improvement and
changed immunosuppressive regimen after tumor diagnosis. regression of hypercalcemia to normal values. In February
The patient with renal pelvis TCC had a double kidney 2009 a CT evaluation showed stable disease, and in March
transplantation. The tumor was diagnosed 4 years after the 2009 a skeletal scintigraphy revealed complete response of
transplantation because of hematuria. A nephroureterectomy bone metastases. Treatment was well tolerated (with exception
of the involved graft was performed. A pT3G3 TCC was of grade I asthenia) and was continued until May 2009, when

1950
 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

patient experienced diffuse bone pain, recurrence of confirmed stable disease. Conclusion: This case suggests that
hypercalcemia, severe anaemia and altered liver function tests. even in poor-risk mRCC a sequential targeted treatment may
Given the severity of symptoms we decided to start a second determine a relevant benefit in terms of quality of life and, in
line of biological therapy without waiting for baseline CT selected cases, may induce long term survival.
evaluation. In consideration of the patient’s fears about
Sunitinib-related cardiotoxicity and our willingness to reserve
this therapeutic option for an eventual third line therapy, we 167
chose to begin Sorafenib. This treatment (400 mg twice daily) ASSESSMENT OF THE ROLE OF PSA,
was initiated at the beginning of June 2009. After eight weeks PRO-PSA, PCA3 AND PROSTATE MRI IN
of therapy we observed a significant improvement in clinical SELECTING PATIENTS WHO ARE CANDIDATES
condition and laboratory parameters (regression of FOR A SECOND PROSTATE BIOPSY
hypercalcemia, increase of haemoglobin level) The patient
Cristian Fiori1, Fabrizio Mele1, Matteo Manfredi1,
didn’t submit to scheduled CT scan and asked not to be
Filippo Russo2, Antonino Sottile3, Enrico Bollito4,
subjected to further imaging studies because of his poor
Mauro Papotti4, Francesco Porpiglia1
clinical conditions, so we couldn’t achieve a baseline
radiological disease evaluation. Since our primary objective 1Divisione di Urologia, AOU San Luigi Gonzaga,
was patient’s quality of life and in consideration of clinical, Orbassano, TO;
haematological and biochemical improvement we decided to 2Divisione di Radiologia, IRCC Candiolo, Torino;

continue Sorafenib. After 4 months of treatment the patient 3Laboratorio Analisi, IRCC Candiolo, Torino;

interrupted all analgesic therapy and showed further 4Divisione di Anatomia Patologica, AOU San Luigi

improvement of clinical condition. Biochemical evaluation Gonzaga, Orbassano, TO, Italy

revealed resolution of anaemia and normalization of liver
function tests. Treatment side-effects were grade I asthenia and Introduction: In patients with persistently elevated PSA and
grade I diarrhoea. In November 2009 he developed poorly negative biopsy, there is a need for repeated prostate biopsy.
tolerated grade II hand-foot syndrome which required a The repetition of the biopsy, however, does not increase the
temporary interruption of Sorafenib. Two days after detection rate of PCa, which decreases progressively in the next
discontinuation of the treatment the patient reported complete sampling, leading to an increase of side-effects. Additional
resolution of symptoms, so we decided to resume Sorafenib analyses have been proposed to reduce the number of repeated
without any dose reduction. In January 2010 a CT indicated biopsy (RB) such as pro-PSA, PCA3, and prostate
stable disease compared to the last examination, which had multiparametric Magnetic Resonance Imaging (mp-MRI). Aim
shown best response to Temsirolimus. In June 2010 the of this study was to evaluate the role of these additional
Sorafenib dose was reduced to 600 mg daily because of liver analyses using a diagnostic pathway in patients with clinical
transaminases elevation. This dose reduction led to a rapid suspicion of cancer and/or elevated PSA with an initial negative
normalization of liver function tests. Our patient is still on prostate biopsy. Patients and Methods: We prospectively
treatment with Sorafenib (600 mg daily) after more than three included patients with a negative first biopsy (12 samples) and
years, his Karnofski PS is 100%, liver function tests, calcium abnormal PSA levels, pathological (as ASAP and/or HG-PIN)
and haemoglobin levels are normal and a recent CT scan has or strong clinical suspicion, as shown in Figure 1. Each of them

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

underwent serum pro-PSA measurement, analysis of urine after Introduction: Nowadays, in case of laboratory or clinical
prostatic massage for the assessment of genetic markers, suspicion of Prostate Carcinoma (PCa), the patient is
urinary PCA3 and MRI performing a conventional study with subjected to random biopsies TRUS-guided. Due to the lack
T1-w, T2-w and diffusion sequences. After precontrast of appropriate techniques for the precise localization of PCa,
acquisitions, patients were intravenously given gadobutrol. All often treatment is not the most appropriate. Using an imaging
images were examined by an expert uro-radiologist. All examination that allows us to have a correct radio-histological
patients were then submitted, according to current European correlation can help the clinician in proper planning of
guidelines, to a RB(18 samples), examined by an expert uro- surgery. The aim of our study was to analyze separately each
pathologist. We evaluated sensitivity, specificity, positive and tumor focus to evaluate the diagnostic accuracy of
negative predictive values, and accuracy of the individual tests multiparametric Magnetic Resonance Imaging (mp-MRI) in
and the combination of these to predict the presence of PCa at detecting and localizing of PCa. The study was conducted
the repeated (second) biopsy. Results: 50 patients were prospectively and as gold standard was considered the
consecutively enrolled in the study, the mean age was 62.5 pathological findings in patients undergoing Radical
years, mean PSA at baseline was 7.25 ng/ml. On RB, 15/50 Prostatectomy (RP). Patients and Methods: The study
(30.0%) had biopsies positive for cancer. included 120 patients with high PSA value and biopsy
diagnosis of PCa. All patients underwent MRI performing a
conventional study with T1-w, T2-w and diffusion sequences.
After precontrast acquisitions, patients were intravenously
PCA3 pro- MRI PCA3 pro- PCA3 PCA3 given gadobutrol. All images were examined by an expert
PSA + pro- PSA + MRI + pro-
uro-radiologist. The sensitivity in identifying lesions was
PSA + MRI PSA
+ MRI
defined as the ratio between the number of true positives (i.e.
lesions identified histologically recognized as such in MRI)
Sens 66.7% 53.3% 93.3% 73.3% 93.3% 100.0% 100.0% and the total number of lesions histologically recognized. We
Spec 97.1% 57.1% 91.4% 85.7% 94.3% 94.3% 94.3% stratified the sensitivity according to tumor volume,
PPV 90.9% 34.8% 82.4% 68.8% 87.5% 88.2% 88.2% examining changes less than 0.2 cc, between 0.2 cc and 0.5
NPV 87.2% 74.1% 97.0% 88.2% 97.1% 100.0% 100.0% cc and greater than 0.5 cc. Where defined positive for the
Accuracy 88.0% 56.0% 92.0% 82.0% 94.0% 96.0% 96.0%
presence of neoplastic tissue, hypointense glandular areas in
T2-w, with low ADC values (≤1.1 sec/mm2) and showing an
early impregnation peak followed by washout in DCE-MRI.
Conclusion: We disclose the low number of enrolled patient The lesions were considered as positive for Extra-Capsular
as a main limit of the study. Our results show that the PCA3 Extension (ECE) if they had a large degree of contact or if
test is the one with the highest PPV, while the highest NPV is we observed the presence of neoplastic tissue in the
obtained with the combination of the mp-MRI and the PCA3. periprostatic tissue. It was attributed Seminal Vesicles
The measurement of pro-PSA does not add useful data to the Invasion (SVI) when a lesion of the base had a margin of
combination PCA3 + MRI, which is shown to be the best contact with the vesicles or if we observed the presence of
predictive combination for the diagnosis of PCa. We think hypointense tissue on T2-w and contrast impregnation.
that these preliminary results are promising even if further Results: 232 PCa tumor foci were found in histopathological
cases are necessary to define which patients should be examination. The sensitivity for lesions <0.2 cc was 40.7%
candidate for RB. (24/59); from 0.2 to 0.5 cc was 42.5% (17/40); >0.5 cc was
91% (121/133). The MRI assessment of ECE has shown
sensitivity, specificity, PPV, VPN and accuracy of 88.1%,
168 91.1%, 68.5%, 97.2% and 90.5%, respectively. The MRI
CAN POST-BIOPSY MRI HELP THE SURGEON evaluation of SVI has provided values of sensitivity,
ON SURGICAL PROCEDURE PLANNING? specificity, PPV, VPN and accuracy 86.7%, 99.1%, 86.7%,
99.1% and 98.3% respectively. Conclusion: Our study
Cristian Fiori1, Fabrizio Mele1, Marco Lucci Chiarissi1,
showed that MRI has high accuracy in staging PCa, more
Massimiliano Poggio1, Francesca Ragni1, Filippo Russo2,
than most of the studies in the literature. MRI has a high
Enrico Bollito3, Francesco Porpiglia1
sensitivity to localize the lesions with a volume greater than
1Divisione di Urologia, AOU San Luigi Gonzaga, 0.5 cc, which are the most frequent and statistically are more
Orbassano, TO; likely to progress. Furthermore it has a high VPN against the
2Divisione di Urologia, IRCC Candiolo, Torino; ECE and SVI (97.2% and 99.1% respectively). Thanks to
3Divisione di Anatomia Patologica, AOU San Luigi these promising results, we can make the best choice in
Gonzaga, Orbassano, TO, Italy treatment planning.

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

169 since both Roach formula and risk classification depend on the
ROACH FORMULA AS A GUIDE TO same prognostic factors. Conclusion: The literature from the
TARGET VOLUME SELECTION IN post-PSA era shows that there may be a benefit from WPRT
PROSTATE CANCER RADIOTHERAPY: for pts estimated to be at high risk (>15%) for pelvic lymph
A SINGLE INSTITUTION EXPERIENCE node involvement. Even if WPRT remains controversial, Roach
formula is a simple tool to assess nodal risk, summarizes the
Girolamo Spagnoletti, Anna Maria Leo,
main prognostic factors, reflects and quantifies risk
Rita Marchese, Grazia Nardella, Raffaella Rignanese,
classification and can help radiation oncologists to choose the
Maria Enfasi, Giuseppe Bove
best target volume for each patient. As suggested by some
Struttura Complessa di Radioterapia, Azienda Ospedaliero- studies, it is likely that WPRT may not benefit pts with a very
Universitaria Ospedali Riuniti Foggia, Italy high risk of nodal disease and values of the Roach formula
beyond a certain cut-off. More trials are needed to identify
Introduction and Aim: Whole pelvis radiotherapy (WPRT) is which pts would benefit from such treatment and to clarify the
controversial in the management of prostate cancer. The role of the Roach formula in the radiotherapy practice.
estimation of the risk of pelvic lymph node involvement in
prostate cancer patients (pts) can help to identify those who 1 Roach M, Marquez C, Yho H et al: Predicting the risk of
will potentially benefit from WPRT. Nomograms and equations lymph node involvement using the pre-treatment prostatic
based on pre-treatment PSA, Gleason score and/or clinical specific antigen and Gleason score in men with clinically
stage allow clinicians to quickly estimate nodal risk. Among localized prostate cancer. Int J Radiat Oncol Biol Phys 28:
these tools, the formula proposed by Roach (1) is the simplest 33-37, 1994.
one. The Radiation Therapy Oncology Group (RTOG) enrolled 2 Roach M, De Silvio C, Lawton V et al: Phase III trial
9413 pts with an estimated risk of lymph node involvement of comparing whole-pelvic versus prostate only radiotherapy
at least 15% based on the Roach formula and showed a and neo-adjuvant versus adjuvant combined androgen
progression-free survival benefit with WPRT (2). Our study suppression: RTOG 94-13. J Clin Oncol 21: 1904-1911,
aims to investigate retrospectively the role of the Roach 2003.
formula in the everyday activities of a department of
radiotherapy. Patients and Methods: Two hundred and twenty
men with prostate cancer were treated with 3D-conformal 170
radiotherapy at the Radiotherapy Department in Foggia, from COMPUTER AIDED DIAGNOSIS FOR
October 2006 to February 2011: 159 of them received prostate PROSTATE CANCER DETECTION IN
only radiotherapy (PORT), the others were referred for WPRT. THE PERIPHERAL ZONE BY MRI
All pts did not undergo surgery and 82.7% of them received
Cristian Fiori1, Fabrizio Mele1, Riccardo Bertolo1,
hormonal therapy. According to prognostic factors (pre-
Marco Cossu1, Filippo Russo2, Simone Mazzetti2,
treatment PSA, Gleason score and clinical stage), pts were
Valentina Giannini2, Daniele Regge2, Francesco Porpiglia1
grouped in classes of risk. For each patient, the value of the
Roach formula was calculated with the equation +LN =(2/3) 1Divisione di Urologia, AOU San Luigi Gonzaga,
PSA + [(GS – 6) ×10]. Results were analyzed with non- Orbassano, TO;
parametric methods. The Roach formula values in fact were not 2Divisione di Radiologia, IRCC Candiolo, Torino, Italy

normally distributed (Shapiro-Wilk normality test). The R

statistical program was used. Results: None of the pts with low- Introduction: Prostate carcinoma (PCa) is the most common
risk cancer received WPRT while more than a half of the pts malignancy in men and represents the third cause of cancer
with highrisk disease underwent WPRT. There is a strong death in industrialized countries. Magnetic resonance
association between class of risk and irradiated volumes imaging (MRI) has been promising in localizing PCa and it
(p<0.01, Pearson’s Chi-squared test). Median values of the is largely exploited in clinical routine to visualize and
Roach formula were 15.3 and 37.0 in the PORT and in the characterize tumours, thus improving the detection and
WPRT group, respectively. There is a very significant staging of prostate cancer. An additional value can be given
difference between the values of the Roach formula in the two by Computer Aided Diagnosis (CAD) systems in helping
groups (p<0.01, Wilcoxon rank sum test). This is a radiologists in the diagnosis of prostate cancer. The aim of
confirmation that radiation oncologists, with or without the this study is to develop a CAD system to detect and localize
calculation of the formula, were led by risk factors included in tumour masses, based on T2-w and DCE-MRI images. The
the formula while choosing target volumes. It is not surprising CAD will produce the pixel-wise malignancy probability
that the values of the Roach formula were very different among map in a given region of interest (ROI) of the prostate
the three classes of risk (p<0.01, Kruskal-Wallis rank sum test) gland. Patients and Methods: After an initial phase in which

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

we built this CAD system and we validated its reliability, Andrea Minervini, Sergio Serni, Gianni Vittori, Agostino
we decided to test 10 patients with a biopsy confirmed PCa. Tuccio, Giampaolo Siena, Matteo Salvi, Arcangelo
All of them underwent MRI performing a conventional Sebastianelli, Andrea Chindemi, Riccardo Fantechi, Saverio
study with T1-w, T2-w and diffusion sequences. After Giancane, Michele Lanciotti, Annalisa Mantella, Alberto
precontrast acquisitions, patients were intravenously given Lapini, Marco Carini
gadobutrol and a total of 28 phases were acquired, each
lasting 13 seconds. All images were examined by an expert Clinica I, AOU Careggi, Dipartimento di Urologia,
radiologist on the basis of histological information provided Università degli Studi di Firenze, Italy
after surgery and a total of 13 tumours, all located in the
peripheral zone (PZ), were detected. A ROI was drawn Introduction and Objectives: Simple enucleation (TE) showed
around each lesion, on all possible slices to cover the whole excellent oncological results in large retrospective series. No
tumour extension. When possible a ROI on a healthy region, study has compared oncologic outcomes after TE and radical
with dimension comparable to that of the corresponding nephrectomy (RN) for the treatment of pT1 RCC. The aim of
malignant ROI was also drawn for each patient. Information the present study is to compare the oncologic outcomes after
of pixels belonging to the same ROI were extracted from TE and RN in pT1 RCCs. Patients and Methods: We
both T2-w sequence and the 28DCE volume acquisitions, to retrospectively analyzed 475 patients who underwent TE or
construct time-intensity curves over time. A filtering RN for pT1 RCC, N0, M0 between 1995 and 2007. TE was
operation was performed to reduce noise contribution and done in 332 patients, while RN in 143. Local recurrence,
signal to noise ratio was estimated to discard low quality progression-free survival (PFS) and cancer-specific survival
data. T2-w images were used to evaluate mean grey value (CSS) were the main outcomes of this study. The Kaplan-
of pixels on selected ROIs, while DCE-MRI points were Meier method was used to calculate survival functions, and
analyzed applying three different quantitative models (Tofts, differences were assessed with log-rank statistics. Univariate
Weibull, EU1) and a semiquantitative description (peak and multivariate Cox regression models were also used.
location and maximum enhancement, initial slope, curve Results: The surgical margin status of tumors that had TE was
wash-out, area under the curve). A total of 13 features were always negative. The mean follow-up was 72±44 mo after RN
collected for each pixel. The initial features set was reduced and 58±38 mo after TE (p=0.0004). At last follow-up, 393
in order to avoid over-fitting problems and to discard patients (82.7%) were alive and disease free and 56 (11.8%)
redundant information. Furthermore when a couple of had died of other causes. Overall, 26 patients experienced
highly correlated features occurred, the parameter of the progressive disease (5.4%) and of those 5 were alive but with
couple with lower performances rate was discarded. On the disease progression (1%) and 21 (4.4%) had died of metastatic
basis of these elaboration steps a 6-dimensional vector was disease. No local recurrences were observed in the patients
generated for all the pixels in which model fitting was who underwent RN. Overall, 3 patients with pT1a RCC
successful. Malignancy probabilities were then calculated developed isolated renal recurrence after TE and this was
with the Bayes rule. Results: The resulting area under the always elsewhere in the kidney. Specifically, all patients
receiver operating characteristic (ROC) curve was 0.874; diagnosed having local recurrences had negative surgical
sensitivity and specificity were 84.6% and 83.4% margins. The 5- and 10-yr PFS estimates were 91.3% and
respectively. Good separation between malignant and benign 88.7% after RN and 95.3 and 92.8% after TE (p=NS). The 5-
points can be observed for the three combination of and 10-yr CSS estimates were 92.1% and 89.4% after RN and
parameters shown on the Scatter plots of the three 94.4% (5- and 10-yr CSS) after TE (p=NS). No statistically
quantitative models implemented. Conclusion: The CAD significant differences between RN and TE were found after
scheme presented in this study shows good performance in adjusting CSS probabilities according to age at surgery (≤65
discriminating between benign and malignant regions in the yr, log-rank p-value: 0.99; or >65 yr, log-rank p-value: 0.14),
prostate. This system achieves a high sensitivity and grade (Fuhrman nuclear grades 1-2, log-rank p-value: 0.48;
specificity, leading to a better lesion detection rate. Future grade 3, log-rank p-value: 0.89; or grade 4, log-rank p-value:
developments will focus on integrating the dataset with 0.62), stage (pT1a, log-rank p value: 0.46; or pT1b, log-rank
information from diffusion, in order to further improve p-value: 0.44) or clear cell subtype (log-rank p-value: 0.37).
system performances. Surgical treatment failed to be a predictor of PFS or CSS both
at univariable and multivariable analyses. The potential
limitation of the present study includes that the data originate
171 from a retrospective review. Conclusion: TE can achieve
SIMPLE ENUCLEATION VERSUS RADICAL oncologic results similar to those of RN for the treatment of
NEPHRECTOMY IN THE TREATMENT OF pT1 RCCs provided tumors are carefully selected based on
pT1a AND pT1b RENAL CELL CARCINOMA their safe and complete removal.

1954
 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

172 (p=0.049), the involvement of UCS (p=0.029) and renal sinus

EXTERNAL VALIDATION OF PADUA (p=0.036), the tumor diameter (p=0.021) and the PADUA
CLASSIFICATION FOR THE RENAL score (p=0.0007). At multivariate analysis, among all the
TUMOR ENUCLEATION TECHNIQUE anatomical variables, only PADUA score was found to be an
independent predictor of overall surgical complications
Andrea Minervini, Gianni Vittori, Matteo Salvi,
(p=0.016), and Clavien grade III surgical complications
Giampaolo Siena, Agostino Tuccio, Andrea Chindemi,
(p=0.008). The surgical indication was also an independent
Riccardo Fantechi, Arcangelo Sebastianelli,
predictor of major surgical complications (p=0.029).
Omar Saleh, Sergio Serni, Alberto Lapini, Marco Carini
Conclusion: The PADUA score was significantly associated
Clinica I AOU Careggi - Dipartimento di Urologia, with the parameters of technical difficulty of TE, and it was
Università Degli Studi Di Firenze, Firenze an independent predictor of overall and major surgical
complications of this technique.
Introduction: To assess the ability of PADUA score to predict
the surgical results and the peri-operative complications of
open tumor enucleation (TE) technique for renal tumors. 173
Patients and Methods: Between July 2006 and March 2011, PREDICTORS OF ACUTE GENITO-URINARY
we prospectively gathered data from 244 consecutive patients TOXICITY AFTER HIGH-DOSE PROSTATE
treated with open TE with warm ischemia. All clinical and CANCER RADIOTHERAPY: INITIAL
surgical data of patients and tumors were registered. Among RESULTS OF A PROSPECTIVE STUDY
the parameters of PADUA score, clinical tumor dimension,
Viviana Carillo1, Cesare Cozzarini2, Tiziana Rancati3,
polar, face and rim location, and relationship with UCS were
Alessandro Muraglia4, Claudio Degli Esposti5, Giuseppe
prospectively assigned. Instead, the tumor relationship with
Girelli6, Vittorio Vavassori7, Sergio Villa8, Riccardo
renal sinus was retrospectively assigned. The relationship
Valdagni9, Claudio Fiorino10
between preoperative variables (including PADUA score) and
surgical results/perioperative complications was assessed with 1Fisica Medica, Istituto Scientifico San Raffaele, Milano;
univariate analysis (Spearman correlation coefficient, unpaired 2Department of Radiation Oncology, Istituto Scientifico San
t-test, and Pearson’s chi square test, as appropriate). A Raffaele, Milano;
multivariate logistic regression model was done to test the 3Prostate Cancer Program, Fondazione IRCCS, Istituto

ability of PADUA score, with the other significant variables, to Nazionale dei Tumori, Milano;
predict overall surgical complications and Clavien grade 3 4Department of Radiation Oncology, Arcispedale SM Nuova

surgical complications. Results: The median PADUA score of Di Reggio Emilia, Reggio Emilia;
renal tumors was 8 (IQR:7-9), and it was ≥10 in 52 (21.3%) 5Department of Radiation Oncology, Ospedale di Bellaria;

patients. The mean WIT was 16.8 min. The mean operative 6Department of Radiation Oncology, Ospedale ASL 9 di

time was 109.4 min and the mean EBL was 183.0 mL. Ivrea;
Overall, 47 perioperative complications occurred in 45 patients 7Department of Radiation Oncology, Humanitas - Gavazzeni,

(45/244=18.4%); of these, 39 (16%) were surgical and 8 Bergamo;

(3.3%) medical. Surgical complications included blood loss 8Department of Radiation Oncology 1, Fondazione IRCCS,

treated with bedrest in 2 patients (0.8%), with transfusions in Istituto Nazionale dei Tumori, Milano;
25 (10.2%) and with a second invasive procedure in 5 (2.1%) 9Prostate Cancer Program, Dept. of Radiation Oncology 1,

patients. Urinary fistula occurred in 7 patients (2.9%); it was Fondazione IRCCS Istituto Nazionale dei Tumori, Milano;
treated with bedrest and antibiotics in 4 (1.7%), while it 10Department of Medical Physics, Istituto Scientifico San

needed ureteral stenting in the other 3 cases (1.2%). Two Raffaele, Milano, Italy
patients had two surgical adverse events each (urinary fistula
and blood loss). According to Clavien system, 6 surgical Background and Purpose: In April 2010, a prospective
complications were grade I (2.5%), 25 grade II (10.2%), and 8 observational study (DUE01) aimed at developing
grade III (3.3%). No grade IV and V surgical complications quantitative predictive models of genito-urinary (GU) toxicity
occurred in this series. At univariate analysis the entirely and erectile dysfunction after high dose (≥70Gy) external
endophytic tumor growth, the involvement of UCS and renal radical radiotherapy (RT) for clinically localized prostate
sinus, the clinical diameter and the PADUA score resulted cancer was activated. The aim of this first analysis was to
significantly correlated with WIT and EBL. Only PADUA assess predictors of GU symptoms during treatment scored
score and surgical indications resulted as significant predictors by IPSS and ICIQ-SF. Patients and Methods: A questionnaire
of operative time. Significant predictors of overall surgical collecting detailed clinical information was filled before RT;
complications were the entirely endophytic tumor growth four questionnaires on QoL, GU and erectile dysfunction

1955
 ANTICANCER RESEARCH 32: 1843-1966 (2012)

(QLQ-C30, IPSS, ICIQ-SF, IIEF) had to be completed by Arcangelo Sebastianelli, Matteo Salvi,
patients before RT, at its end, at 3 months and every 6 months Graziano Vignolini, Alberto Lapini,
up to 5 years after RT. Full 3D planning data were collected Sergio Serni, Marco Carini
and analysed with a dedicated program (Vodca, MSS GmbH,
Zurich). The current analysis considered the variation of IPSS Clinica I AOU Careggi, Dipartimento di Urologia, Università
and ICIQ-SF scores between baseline and RT conclusion. In degli Studi di Firenze, Firenze, Italy
particular, an IPSS≥15 at the end of RT was focused on as
the main end-point. Logistic uni-variable and stepwise Objectives: Laparoscopic partial nephrectomy (LPN) is
multivariate (MVA) analyses were performed; Spearman and oncologically safe for the treatement of renal masses with
paired samples t-tests were carried out testing continuous advantages of mininvasive surgery. Open Tumoral Enucleation
variations between baseline and end-RT scores. Results: At (TE) ensures excellent oncological safety allowing maximum
the time of analysis (Dec 2011), 160 patients had been preservation of functional kidney tissue. We report our
enrolled by 7 Institutes. 118/160 patients’ basal and end-RT laparoscopic and robot-assisted TE experience (LTE),
questionnaires were analysed. In the group of patients with describing our surgical technique and veryfing the feasibility
baseline IPSS≥15, the IPSS score remained unchanged (n=13; and the possible indications. Patients and Methods: From
average: 17.9 vs. 18.8, p=0.80), while it significantly November 2007 to December 2010, 93 patients underwent
worsened for the others (n=105; 11.6 vs. 6.9, p<0.0001). On LPN. We performed 15 (16%) LTE and 78 LPN. After
the other hand, in the group of patients with basal ICIQ- location of the lesion, the limit between tumour and safe tissue
SF≥10, ICIQ-SF improved (n=13, 4.3 vs. 10.9, p=0.0002), was delineated by a monopolar hook. Then the vascular
while it slightly worsened for the others (1.6 vs. 0.9, p=0.02); pedicle was clamped and the mass was enucleated by blunt
the ICIQ-SF improvement was proportional to the initial dissection and by scissors using the aspirator for dissection
ICIQ-SF value (p<0.0001). At MVA (overall p=0.001), the too. If identified the peritumoral capsule was isolated by blunt
main independent predictors of IPSS≥15 at RT-end were: dissection using the natural cleavage plane between the
initial IPSS (OR:1.12, p=0.01), use of hypertensive drugs peritumoral capsule and normal parenchyma. Then resection
(OR:4.0, p=0.02) and hypofractionation (2.5-2.65 Gy/fr vs. bed is sutured by a running suture with Monocryl 3-0. Then
1.8-2.0 Gy/fr, OR:3.3, p=0.05). Concerning DVH/DSH resection bed was filled by sealants as FloSeal and oxidize
analysis, data of 85/118 patients were available; in the cellulose sheets as Tabotamp and renorraphy was finished by
hypofractionated subgroup (n=45), the fractions of absolute interrupted or double sutures with Vicryl 2-0 across renal
volume/surface receiving more than 72-74 Gy (V72-74Gy, capsule or by sliding-clip technique. Results: For cortical
S72-74Gy) were correlated with IPSS≥15 at the end of RT; tumours (CT), LTE and LPN were performed respectively in 5
the best cut-off value assessed by ROC analysis was (5/55; 9%) and 50 (50/55; 91%). For corticomidollar tumours
S74Gy>14cm2 (OR:4.9, p=0.02). Conclusion: These (CMT), LTE and LPN were performed respectively in 10
preliminary results of the DUE 01 study show initial IPSS, (10/38; 26%) and 28 (28/38; 74%) cases .Regarding location
hypertension and hypofractionation as independent predictors of the masses, LTE was always performed for peri-hilar
of IPSS≥15 at RT-end in a population of patients tumoral masses (4 cases) and in 11 tumoral masses (11/89;
prospectively followed. Despite the relatively low number of 12%) with other location. The median (range) pathological
DVH/DSH, the fraction of bladder surface/volume receiving size of tumours treated by LTE was 2.6 (1.2-5.3) cm and the
“high-doses” was correlated with IPSS≥15 in the median operative time was 134 min. The median (range)
hypofractionation subgroup. These initial results will be better ischemia time was 21 (12-35) min. The median (range)
refined after completing the enrolment, expected at the end operative blood loss was 340 (100-1500) cc. We found
of this year. The study is supported by a grant from intaoperative bleeding in 2 (13.3%) cases, both for incomplete
Associazione Italiana Ricerca sul Cancro (AIRC-IG8748) clamp with need of hemotransfusions. Then we found 1(6.6%)
case of urinary fistula treated by positioning of double j
uretheral stent. The medium time of drain removal was 3 (2-
10) days. Histopathological analysis revealed no positive
174
surgical margins. We found no local recurrence during a
LAPAROSCOPIC AND ROBOT-ASSISTED TUMORAL
median (range) follow-up of 15 months (1-37). Conclusion:
ENUCLEATION FOR TREATMENT OF SMALL
LTE is a feasable technique even if not absolutely
RENAL MASSES: PRELIMINARY EXPERIENCE
recommended for pT1a tumours, except for the treatment of
AND EXAMINATION OF POSSIBLE INDICATIONS
peri-hilar masses when LTE let a better preservation of
Andrea Minervini, Giampaolo Siena, Agostino Tuccio, functional renal tissue and near structures. LTE has a low rate
Gianni Vittori, Lorenzo Masieri, Andrea Chindemi, of perioperative complications and, as OPN, is not associated
Riccardo Fantechi, Saverio Giancane, with a major risk of positive surgical margins.

1956
 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

175 Agostino Tuccio1, Andrea Minervini1,

PERITUMORAL PSEUDOCAPSULE INVASION Maria Rosaria Raspollini2, Giampaolo Siena1,
DOES NOT AFFECT THE RISK OF LOCAL Matteo Salvi1, Arcangelo Sebastianelli1, Andrea Chindemi1,
RECURRENCE AFTER TUMOR ENUCLEATION IN Riccardo Fantechi1, Lorenzo Masieri1, Gianni Vittori1,
THE TREATMENT OF RENAL CELL CARCINOMA Alberto Lapini1, Sergio Serni1, Marco Carini1
Andrea Minervini1, Maria Rosaria Raspollini2, 1Clinica I AOU Careggi, Dipartimento di Urologia,
Agostino Tuccio1, Giampaolo Siena1, Claudia Giannessi1,
Università degli Studi di Firenze, Firenze;
Lorenzo Masieri1, Riccardo Fantechi1, Andrea Chindemi1, 2Dipartimento di Patologia, Università degli Studi di Firenze,
Gianni Vittori1, Omar Saleh1, Arcangelo Sebastianelli1,
Firenze, Italy
Matteo Salvi1, Alberto Lapini1, Sergio Serni1, Marco Carini1
1Clinica I, AOU Careggi, Dipartimento di Urologia, Aim: To evaluate the pathological characteristics of
Università degli Studi di Firenze, Firenze; peritumoral capsule and the prognostic impact of capsule
2Dipartimento di Patologia, Università degli Studi di Firenze, penetration on tumor recurrence in patients treated by
Firenze, Italy nephron-sparing surgery (NSS) for clear cell RCC. Patients
and Methods: Between January 2005 and December 2007,
Introduction: Peritumoral pseudocapsule (PS) invasion after 115 consecutive patients with single sporadic clear cell RCC
tumor enucleation (TE) in the treatment of renal cell had NSS. Peritumoral capsule status was carefully analyzed
carcinoma (RCC) could potentially affect the risk of local by two dedicated uropathologists. The degree and the side of
recurrence. The aim of the present study is to prospectively capsule penetration, if present, were evaluated. Results:
evaluate this hypothesis in a consecutive series of patients According to the peritumoral capsule status, in 68 (59.1%)
having TE for RCC. Methods: TE was done by blunt the capsule was intact and free from neoplastic penetration
dissection in 201 consecutive patients using the natural (PC–), while in 47 (40.2%) there were signs of invasion
cleavage plane between the tumor and normal parenchyma. within its layers. Overall, 29.6% had capsular penetration on
Pseudocapsule penetration, surgical margin (SM) status and the parenchymal side (PCK), whereas, 11.3% had
routine clinical and pathological variables were recorded. peritumoral capsule invasion on the perirenal fat tissue side
Results: Overall, 164 tumors were diagnosed as single (PCF). None of the patients had positive surgical margins
sporadic RCCs and thus included in the study. Mean (SD, detected at the pathological examination. Mean (median,
median, range) tumor greatest dimension was 3.5 (1.7, 3.2, range) follow-up was 48 months (46, 25-69). The 5-year
1.0-12.5) cm. At the pathological examination, the PS was cancer-specific and progression-free survival were 91.7% and
intact and free from invasion on the parenchymal side in 89.5%, respectively. The 5-year progression-free survival for
73.2%, while it was penetrated on the parenchymal side in tumors PC–, PCK and PCF was 97%, 96.2% and 48.5%,
26.9% of RCCs. In all cases the SM were negative. Even in respectively (p<0.0001; PC- vs. PCF p<0.0001; PCK vs.
patients with pseudocapsule penetration and invasion beyond PCF p=0.0002). The multivariate Cox model showed PCF to
it, neoplastic cells were separated from the surgical margin by be the sole significant independent predictor of progression-
a thin layer of normal tissue with signs of lymphoplasmocytic free survival. Conclusion: PCF is a significant and
inflammation. The 3-year overall survival was 95.5%. The 3- independent predictor of worse outcome. Patients with clear
year cancer-specific and progression-free survival were 100% cell RCC with intact peritumoral capsule, as well as those
and 96.6%, respectively. After a mean (range) follow-up of 44 with PCK, had an excellent prognosis and these pathological
months (25-69), the true local recurrence rate was 0.6%. None features could possibly add to prognostic nomograms if
of the RCCs with pseudocapsule penetrated on the proved statistically significant in larger series with longer
parenchymal side recurred locally. Conclusion: TE is follow-up.
oncologically safe. Peritumoral pseudocapsule invasion does
not influence the risk of local recurrence when TE is adopted
for the treatment of RCC. 177
MULTIPARAMETRIC MRI AND
SIGNIFICANT PROSTATE CANCER
176
Andrea Fandella1, Francesco Di Toma2
PATHOLOGICAL CHARACTERISTICS AND
PROGNOSTIC IMPACT OF PERITUMORAL 1Urologia,Casa di Cura Giovanni XXIII, Monastier di
CAPSULE PENETRATION IN CLEAR CELL Treviso, TV;
RENAL CELL CARCINOMA AFTER 2 Department of Radiological Sciences, Monastier di Treviso

MINIMAL PARTIAL NEPHRECTOMY TV, Italy

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

Introduction and Objectives: Multi-parametric MRI (mp- Objectives: Repeat biopsy (re-biopsy) has been advocated
MRI) may help rule out clinically significant prostate following the diagnosis of ASAP found in prostate biopsy
cancer. To date, studies have been limited by using whole- specimens. Previous studies of repeat prostate biopsy for
mount specimens from men with a diagnosis of prostate ASAP that report cancer detection rates of 40-70%, are based
cancer on TRUS biopsy as the reference standard, on the sextant biopsy scheme. Currently, extended prostate
incorporating work-up bias. We report on the performance biopsy schemes that incorporate lateral/anterior peripheral
characteristics of mp-MRI using template prostate mapping zone are routinely used by most centres because of the
(TPM) as the reference standard. Patients and Methods: associated increased cancer detection rate when compared to
Institutional review board exemption was granted by the sextant biopsy. Our objective was to determine the prognostic
local research ethics committee. Mp-MRI (T1/T2, dynamic value of multiparametric MRI in men who had a diagnosis of
contrast enhancement and diffusion weighting, 1.5Tesla, ASAP. Methods: We retrospectively evaluated 840 transrectal
pelvic phased array) was performed before TPM in men ultrasound guided prostate biopsies between January 2010
with a raised PSA (n=65), of whom 16 had no previous and December 2011 in our Urologic departments. All patients
cancer diagnosis, and 49 had proven cancer on previous who had the initial pathological finding of ASAP were
TRUS biopsy. Each mp-MRI was reported with knowledge selected to have a MRI and cancer detection rate was
of PSA and patient age, by three uro-radiologists (R1-R3) determined in follow-up. Results: The overall detection rate
experts in prostate MRI. Each prostate was divided into 4 of isolated ASAP lesions was 2.5% (46 patients). Of 46
regions of interest (ROI) and a score of 1 to 5 assigned to patients with isolated ASAP on initial biopsy 44 (98.9%)
each ROI (1 - ‘no cancer’, 5 - ‘highly suspicious’). TPM underwent MRI. In case of positive MRI, a guided biopsy
was performed under general anaesthesia with 5 mm-spaced was performed. The total incidence MRI lesion suspicious of
sampling using a brachytherapy template grid. Analysis was cancer rate was 45.4% (20 patients). At the biopsy 18, of
carried out for all cancers on TPM and two definitions of them had cancer. The other 24 underwent the same to random
clinical significance: Definition 1: Gleason grade ≥4+3 biopsy (12 cores) but only 3 had cancer. Conclusion: Our
and/or ≥6 mm cancer core length (CCL); Definition 2: results suggest that for patients with a PSA between 4 and 10
Gleason grade ≥3+4 and/or ≥4 mm CCL. Results: 85 ng/ml, whose initial biopsy by ten cores contains ASAP but
consecutive men (260 ROIs) with a mean age of years 67 not cancer, the multiparametric MRI could help to avoid
(range 40-76) and mean PSA 6.2 μg/L (range 2.1-43) were rebiopsy. Timing for re-biopsy, how many sample should be
evaluated. 130/260 (50%) of ROIs were positive for any taken on re-biopsy should be performed, and how many times
cancer on TPM. By definition 1 and 2 38/260 (15%) and re-biopsy are still problems to solve. MRI could be the
69/260 (27%) had positive ROIs, respectively. Accuracy answer.
using area under receiver-operator characteristic curve
(AUC) improved from 0.66-0.70 for all cancer to 0.71-0.85
and 0.72-0.83 for clinically significant cancer by definition 179
1 and 2. The negative predictive value of mp-MRI was 0.93- ANDROGEN DEPRIVATION THERAPY
0.97 for definition 1 cancers and 0.85-0.90 for definition 2 INFLUENCES THE UPTAKE OF 11C-CHOLINE IN
cancers, respectively. Conclusion: The high negative PATIENTS WITH RECURRENT PCA: RESULTS OF A
predictive value for clinically significant cancer defined by SEQUENTIAL PET/CT STUDY IN 22 PATIENTS
two thresholds suggests that mp-MRI may play a role in
Riccardo Schiavina, Giovanni Passaretti, Daniele Romagnoli,
ruling-out clinically significant prostate cancer. This finding
Valerio Vagnoni, Francesco Mengoni, Giuseppe Martorana
could be used to address the over-diagnosis burden from
PSA screening by using mp-MRI as a test to identify men Clinica Urologica Azienda Ospedaliera, Universitaria
who could avoid a prostate biopsy. Policlinico S. Orsola Malpighi, Bologna, Italy

Introduction and Objectives: The influence of androgen

178 deprivation therapy (ADT) on 11C-Choline uptake in patients
MULTIPARAMETRIC MRI OF THE PROSTATE with recurrent prostate cancer (PCa) has not yet been clarified
AFTER ASAP DIAGNOSIS and there are no recommendations in the literature about
whether ADT should be discontinued before 11C-Choline
Andrea Fandella1, Francesco Di Toma2
PET/CT. The aim of our study was to investigate this issue by
1Urologia,Casa di Cura Giovanni XXIII, Monastier di means of sequential 11C-Choline positron emission
Treviso, TV; tomography (PET)/CT in patients with recurrent PCa. Patients
2 Department of Radiological Sciences, Monastier di Treviso and Methods: Between September 2003 and September 2011,
TV, Italy 1,623 patients were submitted to 11C-Choline PET/CT for PCa

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

restaging due to biochemical PSA relapse after primary therapy 4Programma Prostata, S.C. Radioterapia 1, Fondazione
or staging before primary treatment in our center. We identified IRCCS, Istituto Nazionale dei Tumori, Milano, Italy
22 patients (mean age 69 years, range 54-82) who fulfilled the
following criteria: (a) patient submitted to at least two 11C- Aim: We here present results on 7 year experience in active
Choline PET/CT scans within 12 months in the setting of surveillance (AS). Patients and Methods: Patients in our
tumour restaging; (b) the first 11C-Choline PET/CT before Institute entered 2 AS protocols: SAINT and PRIAS. The 2
commencing ADT and the second 11C-Choline PET/CT after protocols have some common entry criteria: initial PSA≤10
6 months of ADT administration to assess the effectiveness of ng/ml, DRE≤T2 and GPS≤3+3. SAINT requires max 20%
therapy; (c) confirmation of 11C-Choline PET/CT results by positive cores and max 50% core involvement, while PRIAS
subsequent clinical and imaging follow-up and/or prostatic max 2 positive cores and PSA density<0.2 ng/ml/cc. Follow-
fossa biopsy; and (d) availability of complete clinical and up includes in both cases PSA every 3mos, DRE every 6mos,
pathological data for each patient. Results: The mean PSA was re-biopsy after 1yr of AS. When PSA doubling time (DT)=3-
14.2±47.3 ng/ml (median 6.4, range 0.25-170) before starting 10yrs a yearly repeated biopsy is scheduled. Whenever during
therapy. After at least 6 months of ADT, the PSA value the follow-up the PSADT<3yrs, clinical stage is >T2, the re-
significantly decreased compared to baseline mean biopsies show more than 2 (or 20%) positive cores or
(PSA=3.7±3.5 ng/ml, median 0.75, range 0.01-9.5; p<0.05). GPS>3+3, change to active treatment is advised. Results: 342
Before starting ADT in 21 of 22 patients we had a positive pts were enrolled in AS (February 2012): 120 SAINT and 222
11C-Choline PET/CT (bone and/or lymph-node and/or PRIAS. 215/342 (62.9%) pts are still in AS (median f-up of
prostatic fossa). After at least 6 months of ADT, 16 patients 33mos, range 1.5-96.1; median time in AS 22.5 mos, range
presented a negative 11C-Choline PET/CT and PSA values 1.5-96.1): 6 pts dropped out due to comorbidities, 7 due to
significantly decreased. On the other hand, 4 patients showed a personal choice (anxiety), 20 due to off protocol reasons and
rising PSA value during ADT and 11C-Choline PET/CT 1 due to non-PCa death. 93/342 (27.2%) pts dropped out
demonstrated progression of disease. One patient showed both because of disease progression/reclassification: 17 due to
a stable PSA and PET/CT result. Finally, only one patient PSADT, 76 due to upgrading and/or upsizing at re-biopsy
failed to demonstrate a good correlation between PSA value (41/76 at first re-biopsy). The actuarial treatment free survival
and PET result in whom a decrease in PSA value and a (ATFS) was 81%, 69% and 58% at 15, 27 and 40 months,
progression of the disease was observed. These data indicate respectively. To date, no unfavorable outcome has been
the presence of a relationship between PSA values and 11C- observed. Biopsy-related ATFS is related to PSA density
Choline PET/CT results in ADT responders. Conclusion: ADT <0.10 ng/ml/cc (log-rank test p=0.004, ATFS at 27 mos 84%
is able to significantly modify the uptake of 11C-Choline after vs. 74%), prostate volume >60cc (log-rank test p=0.001,
ADT administration. It is worth noting that the major effect of ATFS at 27 mos 93% vs. 76%) and number of negative cores
ADT on 11CCholine PET/CT was recorded in patients with at diagnosis >5 (log-rank test p=0.035, ATFS at 27 mos 94%
androgen-sensitive PCa, similarly to the effect of ADT on PSA. vs. 76%). Best-fit multivariable Cox proportional hazards
Thus, it can be assumed that in order to enhance the sensitivity model for biopsy-related ATFS resulted in a three-variable
of this imaging technique, ADT should be temporarily model (overall p=0.001, AUC=0.66), including age
interrupted before 11C-Choline PET/CT in recurrent PCa. (continuous variable, p=0.08, HR=1.04), number of negative
cores at diagnosis >5 (protective factor, p=0.16, HR=0.52)
and prostate volume >60cc (protective factor, p=0.04,
180 HR=0.31). Conclusion: AS is feasible in selected men with
ACTIVE SURVEILLANCE IN PROSTATE CANCER: early PCa. 1yr re-biopsy is an important check, which can be
7 YEAR EXPERIENCE used as a diagnostic clarification point. Biopsy-related ATFS
is correlated to age, number of negative cores at diagnosis
Cristina Marenghi1, Tiziana Rancati1,
>5(protective factor, surrogate of mm of non-cancer) and
Maria Francesca Alvisi1, Lara Bellardita1,
prostate volume >60cc (protective factor, which may
Barbara Avuzzi1, Nicola Nicolai2, Sergio Villa3,
underline the difficulty of an adequate biopsy sampling in
Tiziana Magnani1, Nice Bedini3,
patients with high-volume prostate). PSA density is related to
Roberto Salvioni2, Riccardo Valdagni4
ATFS in uni-variable analysis but it resulted to be not
1Programma Prostata Fondazione IRCCS, Istituto Nazionale included in the multivariable model. Better multivariable
Dei Tumori, Milano; models are obtained when more specific endpoints are
2S.C. Urologia, Fondazione IRCCS, Istituto Nazionale dei considered, e.g. upgrading and upsizing separately after 1-
Tumori, Milano; year re-biopsy (see Abstract 155).
3S.C. Radioterapia 1, Fondazione IRCCS, Istituto Nazionale

dei Tumori, Milano; This work was partly supported by Fond Monzino.

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

181 Sunitinib treatment on toxicity degree and patient’s compliance

THE IMPORTANCE OF INTEGRATED over treatment. QoL analysis showed no significant
MULTIDISCIPLINARY STRATEGY IN deterioration of the evaluated items. Fifteen patients (9M, 6F)
THE THERAPEUTIC APPROACH TO with PR or SD underwent integrated locoregional procedures
METASTATIC RENAL CELL CARCINOMA: aiming to optimize the obtained response: thermal ablation for
IMPACT ON OUTCOME AND QUALITY liver metastases in 6 patients, embolization of bone metastases
OF LIFE - A PROSPECTIVE in 5, stereotaxic radiosurgery on lung and brain lesions in 4;
MONOINSTITUTIONAL EXPERIENCE 13 of these patients are alive and disease-free at a median of
14 months from the locoregional procedure, 2 are alive with
Raffaella Palumbo, Federico Sottotetti, Emma Pozzi,
progressive disease, in 2nd line treatment for metastatic
Barbara Tagliaferri, Cristina Teragni, Antonio Bernardo
disease. Conclusion: Our data support the modern global,
Oncologia Medica II, Fondazione Maugeri, IRCCS, Pavia, integrated approach to mRCC, in which the expertise of a
Italy multidisciplinary team (urologist, radiotherapist, interventional
radiologist, oncologist) allows the patients ‘good responders’
Background: In the last ten years the availability of new following an active medical therapy to achieve the best
biological agents introduced deep changes in the global outcome in terms of PFS, QoL and also OS. Another key point
therapeutic approach to metastatic renal cell carcinoma of our work is the possibility to modulate sunitinib
(mRCC). Specifically, the use of tyrosine kinase inhibitors as doses/schedules in the different disease stages, with an easier
1st or 2nd line treatment allows to obtain significant responses management of the adverse events and the preservation of a
with globally manageable toxicities. We have now time and good adherence to long-term therapy, without affecting the
opportunities to plan an ‘up-front’ sequential strategy approach drug efficacy. An important endpoint in the global management
with several drugs and, in the good-prognosis oligo-metastatic of the patient with RCC is the achievement of long-lasting
disease, integrate the medical treatment within a network of disease responses, in view of a sequential and integrated
expertise in order to achieve the best possible response. approach with the utilization of the new biological treatments
Patients and Methods: We report updated outcome of 35 available also in treatment lines following the first.
consecutive metastatic renal cell carcinoma (mRCC) patients
(pts) treated at our Institution with sunitinib (scheduling: 50
mg/day, 4 week on/2 off) in 1st (29 pts) 2nd (6 pts) line therapy 182
from 2006. There were 21 males and 15 females, median age THE NUMBER OF ORGANS AFFECTED
54 years (range 48-80); the most represented metastatic sites BY METASTASES IS ONE OF THE MOST
were bone (23%), liver (26%), lung (34%), nodes (11%). INFORMATIVE PREDICTOR OF RENAL
Histologic subtype was clear cell carcinoma in 80%, papillary CELL CARCINOMA SPECIFIC SURVIVAL
carcinoma in 12 and chromophobe in 2. Median time on IN CANDIDATES TO CYTOREDUCTIVE
treatment for all patients was 28 months (range 12-61). Overall NEPHRECTOMY
survival (OS) and progression-free-survival (PFS) were
Umberto Capitanio1, Marco Roscigno2, Nazareno Suardi3,
measured from initial administration of sunitinib until death for
Richard Naspro2, Rayan Matloob2, Cristina Carenzi3,
any cause or documented disease progression, respectively.
Francesca Ceresoli2, Francesco Montorsi3, Patrizio Rigatti3,
With OS data updated at December 1, 2011, the median
Luigi Da Pozzo3, Roberto Bertini3
follow-up was 36 months (range 12-61), OS and TTP were
calculated according to the Kaplan-Meyer method. Univariate 1Urologia Ospedale San Raffaele, Milano,
and multivariate analysis (Log-rank test and Cox proportional 2Urologia, Ospedali Riuniti di Bergamo, Bergamo,
hazards model) were performed to identify factors potentially 3Urologia, Istituto Scientifico San Raffaele, Milano, Italy

associated with the clinical outcome. Quality of life (QoL) was

assessed by FACT-G score every 2 cycles of therapy. Results: Background: The natural history of patients with metastatic
Twelve partial responses (34%) and 18 stable diseases (51%) Renal Cell Carcinoma (mRCC) is extremely heterogeneous.
lasting >3 months were observed by RECIST criteria, for an In this context, no study has systematically analysed whether
overall global clinical benefit of 85%. Treatment-related the combination of number of metastatic sites and number of
toxicities were expected and were globally manageable: fatigue organs affected by metastases affect survival. Methods:
(42%), thrombocytopenia (25%), hand foot syndrome (15%), Between 1987 and 2011, 1847 RCC patients underwent
macrocytic anemia (10%) hypertension (8%) and neutropenia nephrectomy at a single tertiary care institution. Descriptive,
(5%). Hypothyroidism took place in 21 pts (60%) and was univariable and multivariable Cox regression analyses assessed
treated, when symptomatic, with levothyroxine. Dose reduction the effect of the number of metastases and the number of
and/or scheduling modifications were performed, modulating organs affected on cancer-specific survival (CSS). Adjustment

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

was performed for age, symptoms, performance status, tumor 71-89 yrs). Univariable and multivariable logistic regression
size, Fuhrman grade, pathological T stage, lymph nodal status, analyses addressed the impact of performing RN vs. PN on
and presence of necrosis or sarcomatoid features. Results: renal function worsening and on cardiovascular morbidity. Cox
Among 242 (13.1%) mRCC patients, 151 (62.4%), 67 (27.7%) regression analyses addressed the role of nephron-sparing
and 24 (10.0%) had 1, 2 or more than 2 distant organs surgery on cancer-specific mortality (CSM) and OM. Results:
affected. Specifically, metastases were diagnosed in lung RN was performed in 443 patients and PN in 487. Median
(n=141, 58.3%), bone (n=75, 31.0%), adrenal gland (n=44, follow-up was 61 months (range: 5-283 mos). Thirty-seven
18.1%), liver (n=38, 15.7%), brain (n=27, 11.2%) and other percent of patients who underwent RN had renal function
sites (n=40, 16.5%). Median survival was 32.0 months vs. 9.7 worsening, compared to 16% of patients undergoing PN
vs. 6.8 for patients with 1 vs. 2 vs. more than 2 organs affected (p<0.001). At multivariable logistic regression analysis, PN
(p<0.001). At multivariable analyses, the number of metastatic (p<0.001), younger age (p<0.001) and absence of smoking
organs achieved the independent predictor status of CSS (2 vs. history (p=0.047) were associated with a reduced risk of renal
1 site: HR 1.68 and >2 vs. 1 site: HR 1.62, p=0.01). Lung was function impairment, after adjusting for Charlson Comorbidity
the location with the highest rate of single organ affected Index, gender, presence of hypertension, preoperative eGFR.
(50.3% vs. 35.1% in other sites, p<0.001). Considering only PN was also an independent predictor of reduced risk of
patients with a single metastatic organ, no statistically cardiovascular morbidity (p<0.001), after adjusting for the
significantly different CSS rates were recorded (log rank other confounders. The type of surgery did not achieve the
pairwise p>0.3). Conclusion: Among patients with mRCC, the independent predictor status of CSM or OM, after adjusting for
number of organs with metastases is an independent predictor pT, pN, presence of distant metastases, worsening of renal
of CSS. Patients with multiple organs affected by multifocal function and cardiovascular morbidity. Nonetheless, worsening
disease have significantly poorer survival. Lung metastases of renal function and cardiovascular morbidity were
show slightly better survival relative to other metastatic sites. independent predictors of OM (p=0.07 and p=0.08,
However, when considering only patients with a single organ respectively). Conclusion: PN was significantly associated with
affected, the location of the metastasis did not affect CSS. a reduced risk of worsening of renal function and a reduced
risk of cardiovascular morbidity. PN did not achieve the
independent predictor status of OM. However, renal function
183 worsening and cardiovascular morbidity, both influenced by the
RENAL AND CARDIOVASCULAR type of surgery, were associated with a higher risk of OM.
MORBIDITY AFTER PARTIAL OR RADICAL
NEPHRECTOMY IN PATIENTS WITH KIDNEY
TUMORS UP TO 7 CENTIMETERS: 184
IMPLICATIONS ON OVERALL MORTALITY HOW TO PREDICT CANCER SPECIFIC
MORTALITY IN PATIENTS WITH
Marco Roscigno1, Richard Naspro1, Umberto Capitanio2,
PAPILLARY RENAL CELL CARCINOMA
Rayan Matloob2, Cristina Carenzi2, Francesca Ceresoli1,
Francesco Montorsi2, Patrizio Rigatti2, Umberto Capitanio1, Marco Roscigno2, Firas Abdollah3,
Luigi Da Pozzo1, Roberto Bertini2 Richard Naspro2, Rayan Matloob3, Cristina Carenzi3,
1Urologia, Francesca Ceresoli2, Francesco Montorsi3, Patrizio Rigatti3,
Ospedali Riuniti di Bergamo, Bergamo;
2Urologia, Luigi Da Pozzo2, Roberto Bertini3
Istituto Scientifico San Raffaele, Milano, Italy
1Urologia, Ospedale San Raffaele, Milano;
Objectives: To evaluate the impact of radical nephrectomy 2Urologia, Ospedali Riuniti di Bergamo;
(RN) or partial nephrectomy (PN) on estimated Glomerular 3Urologia, Istituto Scientifico San Raffaele, Milano, Italy

Filtration Rate (eGFR) and cardiovascular morbidity, and

whether it could affect overall mortality (OM) in patients Background: Papillary renal cell carcinoma (PRCC) is the
treated for renal cell carcinoma (RCC) of up to 7 cm. Patients second most common subtype among kidney neoplasms.
and Methods: From 1987 to 2007, 930 consecutive patients Recently, Klatte et al. developed the first tool to predict cancer
underwent surgery at our institution for sporadic RCC of up to specific mortality (CSM) in PRCC patients. Patients and
7 cm of diameter, with a normal contralateral kidney. Renal Methods: Clinical and pathological data were prospectively
Function was evaluated by the Estimated Glomerular Filtration gathered in 177 patients treated with radical nephrectomy or
Rate (eGFR) pre-operatively and at last folow-up. Renal partial nephrectomy at two academic center, between 1991 and
function worsening was defined as a decrease of eGFR below 2010 with a final diagnosis of PRCC. Nomogram predicted
60 ml/min/1.73m2, or as a change of class in renal function. survival probability and actual CSM were compared.
Age was coded as quartile (29-50 yrs; 51-60 yrs; 61-70 yrs and Discrimination was quantified with the area under the receiver

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

operating characteristics curve (AUC). Calibration compared the perspective study was to evaluate the impact of micro-
predicted and the observed cancer rates throughout the entire metastasis assessed by serial section (SS),
range of predictions. Results: At a median 73-month follow-up immunohistochemistry (IHC) and real time-Polymerase Chain
24 papillary renal cell carcinoma related deaths had occurred Reaction (RT-PCR) in patient submitted to radical
(13.6%). T classification was pT1a, pT1b, pT2ab, pT3abc and prostatectomy with extended PLND. Patients and Methods: 32
pT4 in 66 (37.3%), 53 (29.9%), 24 (13.6%), 33 (18.7%) and 1 consecutive patients submitted to radical prostatectomy with
(0.6%), respectively. At nephrectomy, lymph node and distant extended PLND for intermediate (clinical T1c-T2 and PSA:10-
metastases were present in 51 (28.8%) and 13 cases (7.3%), 20 ng/mL and clinical Gleason Score=7) or high (clinical stage
respectively. Grade 1-2 or 3-4 was noted in 137 tumors (77.4%) T3 or PSA>20 or clinical Gleason Score=8-10) PCa were
and 40 (22.6%), respectively. Papillary type 2 was assigned to enrolled. The average probability of nodal invasion with
64 (36.2%) of PRCCs. Necrosis was present in 69 (39.0%) Briganti pre-operative nomogram (Briganti, Eur Urol 2006) of
patients. One, 2, 5 and 10-year cancer specific survival rates the whole population was 26.9% (SD=14.4). Extended PLND
were 95.4%, 91.8%, 86.1% and 84.9%, respectively. External included obturator, internal/external and distal 2 cm common
independent validation revealed 84.6% predictive accuracy. iliac lymph-nodes (LN). The nodes were processed by one uro-
Overall, the tool showed good calibration with minimal pathologist both according to the routine pathological
departure from ideal prediction. Conclusion: We externally examination (analysis of the central section for 4 mm nodes or
validated a highly accurate tool specifically for papillary renal every 2 mm for LN>4 mm), which served as comparative
cell carcinoma using basic clinical and pathological information method, both according to SS, IHC with antibodies against
to predict disease specific survival. This nomogram resulted the PSA and spectrum-cytokeratins (BSCK) and quantitative RT-
most accurate tool to identify papillary renal cell carcinoma PCR targeting PSA, PSMA (PS Membrane Antigen) and
with aggressive clinical behavior and may contribute to the Glucuronidase-S-Beta (GUSB) mRNA, that are over-expressed
ability to individualize postoperative surveillance and therapy. in prostatic cancer cells. Results: A total of 628 LN were
analyzed, with a mean number of LN removed of 19.6
(SD=7.2). Applying the routine pathological examination, 10
185 (31.2%) patients and 23 (3.9%) LN resulted positive for nodal
DETECTION OF NODAL MICRO involvement, with mean positive LN of 2.2 (SD=1.4). After
METASTASES WITH SERIAL SECTION, applying the SS and the molecular methods of analysis (IHC
IMMUNOHISTOCHEMISTRY AND REAL and RT-PCR), micro-metastases were found in 11 LN (SS
TIME-POLYMERASE CHAIN REACTION showed micrometases in 3 of them, IHC in 6 of them and RT-
IN INTERMEDIATE AND HIGH RISK PCR in 7 of them) and a total of 3 (9.3%) node negative
PROSTATE CANCER PATIENTS SUBMITTED patients at routine pathological examination showed
TO RADICAL PROSTATECTOMY WITH micrometastasis (in 2 patients with RTPCR and in 1 with IHC).
EXTENDED PELVIC LYMPH NODE Conclusion: Molecular analysis of the LN can detect a not
DISSECTION: A PERSPECTIVE STUDY negligible percentage of patient who arbour micrometastatic
PCa missed at routine pathological examination and can
Riccardo Schiavina1, Giovanni Passaretti1,
enhance the accuracy of lymphadenectomy as a staging
Daniele Romagnoli1, Alessandro Bertaccini1,
method. Cost-effective analysis are needed. The significance of
Eugenio Brunocilla1, Fabio Manferrari1, Sergio Concetti1,
the micro-metastasis in PCa and the potential therapeutic role
Marco Garofalo1, Valerio Vagnoni1, Cosimo Bizzarri1,
of PLND is not yet clarified but the removal of micro-
Francesco Chessa1, Lorenzo Bianchi1, Michele Provenzale1,
metastases can reduce the rate of nodal disease relapse
Michelangelo Fiorentino2, Giuseppe Martorana1
1Department of Urology, S. Orsola-Malpighi Hospital,
University of Bologna; 186
2Anatomia e Istologia Patologica – Grigioni, AOU S. Orsola NON-INVASIVE, EARLY DIAGNOSIS OF
Malpighi, Università di Bologna, Italy SUPERFICIAL BLADDER CANCER: URINE
CELL FREE DNA INTEGRITY AND CYTOLOGY
Introduction and Objectives: A consistent rate of patients who
Valentina Casadio1, Sara Bravaccini1, Roberta Gunelli2,
are classified as “node-negative” after radical prostatectomy
Michela Tebaldi1, Daniele Calistri1, Marco Giampaoli3,
and pelvic lymph-node dissection (PLND) experience a nodal
Andrea Savini3, Riccardo Cividini3, Manola Marini3,
disease relapse. Routine pathological examination can miss
Alessandro Bertaccini3, Giuseppe Martorana3
micro-metastatic tumor foci in the lymph nodes (LN) of
patients with prostate cancer (PCa), resulting in confused tumor 1Biosciences Laboratory, Istituto Scientifico Romagnolo per
staging and clinical decision-making. The aim of the present lo Studio e la Cura dei Tumori (I.R.S.T.) Di Meldola;

1962
 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

2Department of Urology, Morgagni-Pierantoni Hospital, 1U.O. Radioterapia, Mazzarotto, Azienda Ospedaliero,

Forlì; Universitaria di Bologna S. Orsola, Malpighi, Bologna;
3Department Of Urology, S. Orsola-Malpighi Hospital, 2U.O. Urologia - Martorana, Policlinico Sant’Orsola-

Bologna, Italy Malpighi, Bologna;

3U.O. Radioterapia, Barbieri, Policlinico Sant’Orsola-

Background: It is known that the origin of extracellular DNA Malpighi, Bologna, Italy
can be established on the basis of its fragmentation; non-
cancer apoptotic cells produce highly fragmented DNA Purpose: To assess the feasibility and early toxicity of HDR-
whereas necrotic cancer cells release longer DNA. The aim of BRT dose escalation to biopsy proven and 11C-choline PET-
our study was to verify the accuracy of urine cell free DNA CT visible PC recurrence after EBRT. Patients and Methods:
integrity, alone or in combination with urine cytology, in In March 2011, a 70 year old patient affected by Prostatic
identifying bladder cancers. Patients and Methods: The study Adenocarcinoma (PC), Gleason score (GS) 7 stage T2bN0M0,
was conducted on a series of 129 individuals: 51 cancer treated in 2005 with 74Gy in 37F 3D EBRT for an
patients, 46 symptomatic patients (Lower Urinary Tract intermediate risk, underwent salvage treatment with HDR-
Symptoms) with benign diseases, and 32 healthy volunteers. BRT for a local relapse, reocurred 3 years after the primary
Extracellular DNA was isolated from urine supernatant and treatment by progressive increases of PSA up to 5.5 ng/ml.
free DNA integrity was determined blindly by three Bone scan, endorectal US, 11C-choline PET-CT and serial
quantitative Real Time PCRs on three sequences longer than biopsies, evidenced a relapse of PC, GS 8, confined only in
250 bp: C-MYC, BCAS1 and HER2. A short fragment called the left lobe. MRI was not performed due to a right hip
STOX 1 was analyzed to exclude the presence of PCR prosthesis. HDR-BRT was performed, under epidural
inhibitors. Results: UF DNA integrity analysis highlighted 0.1 anesthesia, in 2 separate fractions at a distance of 3 weeks, by
ng/μl as the best cut-off value with 0.73 (95% CI 0.61-0.85) inserting 17 plastic afterloading catheters using a transperineal
sensitivity, 0.84 specificity (95% CI 0.71-0.97) in healthy transrectal US guided approach. Treatment plan was
individuals, and 0.83 (95% CI 0.72-0.94) in symptomatic performed using dedicated software (Oncentra Prostate™).
patients. The areas under the ROC curves were 0.8346 (95% During each fraction, the dose delivered was 9.5Gy to the
CI 0.7391-0.9300) for healthy individuals and 0.7962 (95% CI entire prostate (CTV1) plus 2.5Gy SB to the left lobe (CTV2)
0.7070-0.8855) for symptomatic patients. In our case series where relapse was histologically and biologically
UF DNA integrity showed higher sensitivity compared to demonstrated. Assuming α/β values of 1.5 for PC, these
cytology (0.73 versus 0.53) with the highest advantage for cumulative doses should be biologically equivalent to 59.7Gy
low-grade tumors (0.72 vs. 0.15). The combination of cytology for CTV1 and to 92.6Gy for CTV2. Dose constraints were:
and UF-DNA analysis increased sensitivity to 0.81(95% CI D90 ≥95% of Target volume, V100 ≥95% of (Prescription
0.69-0.93). Conclusion: Our preliminary data suggest that Dose) PD, V150 ≤30% of the PD, max dose to the urethra
urine cell free DNA integrity has the potential to be a good 1CC ≤125% of the PD, max dose to the rectum 1 CC ≤75% of
marker for the diagnosis of early, non-invasive bladder cancer. the PD. Prostate symptoms were recorded before and after the
The diagnostic performance of the test did not vary BRT using the International Prostate Symptom Score (IPSS).
significantly even when symptomatic individuals instead of Results: CTV1 and CTV2 at the 1^ and 2^ fraction were
healthy individuals were considered as reference group. respectively 44 and 47.4, and 15 and 19 CC, with a 3.5%
Furthermore, sensitivity of UCF DNA integrity could be increase at the 2^ fraction due to postimplant swelling. The
further increased by evaluating it in combination with predefined dose constraints were respected except for the
conventionally used urine cytology. Research is ongoing in a rectum that received a 9% higher dose to the prescribed D
larger case series to confirm these results. max, to allow a CTV2 good coverage. No complications were
recorded during or after BRT procedures. According to the
VAS scale, perineal pain was scored as 4 soon after treatment.
Two months after BRT, the patient reported occasional urinary
187
urgency and pain (VAS scale 1), while the IPSS-score S was 5
SALVAGE HIGH DOSE RATE BRACHYTHERAPY
and QLS1. Two months after treatment, PSA was 1.14 ng/mL,
(HDR-BRT), AFTER PRIMARY EXTERNAL BEAM
while at four and twelve months dosed PSA levels were
RADIOTHERAPY (EBRT) FOR PROSTATE CANCER:
respectively 0.53 ng/mL and 0.13 ng/mL. One year after
A CASE REPORT
treatment patient reports slightly light dysuria. Conclusion:
Giorgio Tolento1, Alessandro Bertaccini2, Marco Giampaoli2, HDR-BRT, performed by delivering differentiated doses inside
Riccardo Cividini2, Debora Marchiori2, Fabrizio Romani1, the prostate parenchyma in a patient with local recurrence
William Gaiba3, Fabio Manferrari2, Riccardo Schiavina2, after EBRT, is feasible and safe. A longer follow-up is
Giuseppe Martorana2, Enza Barbieri3, Renzo Mazzarotto1 necessary to evaluate local control and late effects.

1963
 ANTICANCER RESEARCH 32: 1843-1966 (2012)

188 volume of 57 cc), affected by non-acute urinary symptoms

OBSERVATIONAL DATABASE SERENOA REPENS caused by BPH, a dosed PSA level inferior to 10 ng/ml, a
(DOSSER): OVERVIEW, ANALYSIS AND RESULTS. previous negative prostate biopsy and in therapy with Serenoa
A MULTICENTRIC SIURO (ITALIAN SOCIETY repens alone or associated to an α-blocker, were
OF ONCOLOGICAL UROLOGY) PROJECT retrospectively inserted in an extensive on-line SIUrO
Database. Comprehensive questionnaires were filled in for
Alessandro Bertaccini1, Marco Giampaoli1, Riccardo
each patient at 3 and 6 months of follow-up. Each
Cividini1, Gian Luca Gattoni3, Tommaso Realfonso4, Giorgio
questionnaire contained various sections, each of them
Napodano4, Roberto Sanseverino4, Andrea Fandella5, Elisa
composed by several items: dosed PSA levels,
Guidoni5, Domenico Prezioso6, Raffaele Galasso6, Carmine
uroflowmetry, urinary symptoms (IPSS), erectile function
Cicalese6, Vincenzo Scattoni7, Leonardo Villa7, Angelo
(IIEF-5), trans-rectal ultrasound (TRUS) patterns, digital
Armenio8, Matteo Corinti9, Giovanni Liguori10
rectal examinations (DRE) aspects, previous prostate
1Clinica Urologica Prof. Martorana, Azienda Ospedaliera, bioptical results (histology) and side-effects. Results: PSA
Universitaria Policlinico S. Orsola Malpighi, Bologna; levels weren’t subjected to an increase, revealing a
2U.o. Urologia, Martorana Azienda Ospedaliera Universitaria stabilizing or downward trend. Percentage of patients with
Policlinico S. Orsola Malpighi, Bologna; PSA below the level of 4 ng/mL was significantly lower at
[Link].O, Società Italiana di Urologia Oncologica; the end of the study. The overall changes in the
4UOC-Urologia Ospedale “Umberto 1˚” Nocera Inferiore; uroflowmetry were similar and parallel both in the group
5Urologia, Casa di Cura Giovanni XXIII, Monastier di with only Permixon® intake and in the group with
Treviso; Permixon® plus α-blocker. The mean medium flow and the
6Dipartimento di Scienze Ginecologiche, Ostetriche, mean maximum flow had a slight increase along the
Urologiche e Medicina della Riproduzione, Università di observation time. There was a substantial decrease in the
Napoli; amount of patients presenting severe prostatic symptoms.
7Div. Urologia, Istituto Scientifico H. San Raffaele, Milano, Patients reported through the IIEF-5 score a sexual activity
8Urologia, Ospedale Buccheri, La Ferla, Palermo; substantially unchanged after 6 months of follow-up. The
9Urologia, Ospedale S. Anna, Como; Permixon® intake resulted in an improvement of the
10Clinica Urologica Università Degli Studi di Trieste, “inflammatory-like reports”, in terms of Ultrasound patterns,
Ospedale di Cattinara, Trieste, Italy DRE and bioptical features. Conclusion: Serenoa repens
demonstrated its efficacy reducing dysuria with minimal side-
Background: Men affected with Benign Prostate Hyperplasia effects. Further prospective studies might confirm its
(BPH) and Lower Urinary Tract Symptoms (LUTS) require an stabilization or lowering role on PSA levels in this cohort of
increasing amount of attention from Urologists and Primary- patients and its possible clinical anti-inflammatory action.
care Physicians. Over the years, common urological
medications were based on either α-blockers and/or 5α- 1 Gerber GS and Fitzpatrick JM: The Role of a lipido-sterolic
reductase inhibitors (1-6). In the last decade there has been an extract of Serenoa Repens in the management of lower
increase in the use of plant-derived drugs for many clinical urinary tract symptoms associated with benign prostatic
conditions. Thus the phytotherapeutic drugs are gaining more hyperplasia. BJU International 94: 338-334, 2004.
often a central role in the BPH and LUTS managements. 2 Walsh PC. Benign Prostatic Hyperplasia. In: Walsh PC,
Amongst the various phytotherapeutic agents, the most widely Retik AB, Vaughn ED, Wein AJ eds. Campbell’s Urology,
employed is the extract of the dried ripe fruit of Serenoa 6th Edn. Philadelphia: WB Saunders pp. 1007-1027, 1992.
repens (Sabal serrulata). In particular, clinical usage of 3 Vallancien G and Pariente P: Treatment of lower urinary
Permixon® (Pierre Fabbre Mèdicament, Castres, France) with tract symptoms suggestive of benign prostatic obstruction in
a dosage of 320 mg per day, has shown its clinical efficacy real life practice in France. Prostate Cancer Prostatic Dis 4:
and its superiority (7-11). Purpose of this multicentric 124-131, 2001.
observational retrospective study was to evaluate all the 4 Buck AC: Phytotherapy for the prostate. Br J Urol 78: 325-
urological aspects (clinical, biochemical, instrumental and 336, 1996.
pathological) of patients affected by BPH and LUTS, with a 5 Wilt TJ, Ishani A, Stark G, MacDonald R, Lau J and
PSA <10 ng/ml, a previous negative prostatic biopsy and in Mulrow C: Saw palmetto extracts for treatment of benign
therapy with a daily dose of 320/640 mg of Permixon®. prostatic hyperplasia: a systematic review. JAMA 280(18):
Patients and Methods: The study was conducted in 8 different 1604-1609, 1998.
centers throughout Italy from September 2010 to November 6 Lowe FC and Fagelman E: Phytotherapy in the treatment of
2011. Data and information of 298 men with an average of 63 benign prostatic hyperplasia: an update. Urology 53(4): 671-
years (mean PSA of 5.4 ng/ml and mean prostate gland 678, 1999.

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 Abstracts of the 22nd Annual Meeting of the Italian Society of Uro-Oncology (SIUrO), 13-15 June, 2012, Bologna, Italy

7 Habib FK and Wyllie MG: Not all brands are created equal: present study we evaluated the diagnostic accuracy of 11C
a comparison of selected components of different brands of Choline Position Emission Tomography in combination with
Serenoa Repens extract. Prostate Cancer Prostatic Dis 7: computed tomography (PET/CT) for LN staging in patients
195-200, 2004. with BCa scheduled for RC in comparison with contrast
8 Champault G, Patel JC and Bonnard AM: A double-blind enhanced CT (CECT). Patients and Methods: From April
trial of an extract of the plant Serenoa Repens in benign 2011, 15 patients (mean age 70±9.8), with urothelial bladder
prostatic hypertrophy. Br J Clin Pharmacol 18(3): 461-462, cancer underwent RC with extended (internal, external,
1984. common iliac, presacral and obturator LN) pelvic lymph node
9 Tasca A, Barulli M, Cavazzana A, Zattoni F, Artibani W, dissection (PLND); all patients were preoperatively submitted
Pagano F: Treatment of obstructive symptomatology caused to CECT and 11C Coline PET with low-dose CT for
by prostatic adenoma with an extract of Serenoa Repens. attenuation correction. At PET/CT the node positivity was
Double blind clinical study vs. placebo. Minerva Urol Nefrol defined as the presence of focal uptake in a LN region, while
37(1): 87-91, 1985. at CECT the size criterium (>1 cm) was considered.
10 Cukier J, Ducassou J, Le Guillou M et al: Permixon®® Histopathology of resected LN was taken as reference
versus placebo: result of a multicenter study. CR Ther standard and was correlated with the results of 11C Choline
Pharmacol Clin 4: 15-21, 1985. PET/CT and CECT in a patient-based analysis. Sensitivity,
11 Descotes JL, Rambeaud JJ, Deschaseaux P and Faure G: Specificity, Positive Predictive Value (PPV), Negative
Placebo controlled evaluation of the efficacy and Predictive Value (NPV) and accuracy of both the techniques
tolerability of Permixon®® in benign prostatic hyperplasia were evaluated. Results: Pathological examination of removed
after exclusion of placebo responders. Clin Drug Invest 9: specimen showed an organ confined disease in 8 patients (1
291-7, 1995. CIS, 5 pT1, 2 pT2), while the remaining half of the
population harboured a non-confined disease (6 pT3, 1 pT4.)
A total of 474 LN were removed (mean 31.6±12.4), and
189 metastases were found in 30 LN (6%) and in 3 of 15 patients
ACCURACY OF [11C] CHOLINE POSITRON (20%). According to patient-based analysis, sensitivity,
EMISSION TOMOGRAPHY/COMPUTED specificity, PPV, NPV and accuracy, calculated for [11C]
TOMOGRAPHY IN PREOPERATIVE choline, were 100%, 92%, 21%, 100% and 93%, respectively,
STAGING IN PATIENTS WITH BLADDER while, for standard CT, the values of these parameters were
CANCER REFERRED TO RADICAL calculated as 33%, 91%, 8%, 84% and 80%, respectively. By
CYSTECTOMY (RC): COMPARISON WITH applying a lymph node-based analysis, [11C] choline showed
CONVENTIONAL COMPUTED TOMOGRAPHY (CT) an accuracy of 98% (sens. 10%, spec. 99%, PPV 1%, NPV
99%), while the CT respectively had an accuracy of 93%
Riccardo Schiavina, Giovanni Passaretti, Daniele Romagnoli,
(sens. 3%, spec. 99%, PPV 99%, NPV 93%). Considering the
Alessandro Bertaccini, Eugenio Brunocilla,
3 N+ patients (109 LN removed, mean 36.4±21.5), according
Fabio Manferrari, Sergio Concetti, Marco Garofalo,
to [11C] choline imaging, 4 LN (3%) were found positive for
Cosimo Bizzarri, Francesco Chessa, Lorenzo Bianchi,
metastatic dissemination, though 2 LN (1%) showed false
Michele Provenzale, Giuseppe Martorana
positivity. As far as our population is concerned, in 11 cases
Department of Urology, S. Orsola-Malpighi Hospital, (71%) [11C] choline imaging showed uptake limited to the
University of Bologna, Italy bladder, while in 4 patients (29%) also LN uptake was
detected. Conclusion: Alhough this is still an ongoing study,
Introduction: Lymph node involvement is one of the major the preliminary data collected show an increase in the
prognostic factors in bladder cancer after radical cystectomy, accuracy of the preoperative staging of BCa, by performing
but current imaging techniques are of limited value in the [11C] PET/CT scan in addition to standard CT in patients
prediction of regional and distant metastatic disease. In the referred for RC and PLND.

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 ANTICANCER RESEARCH 32: 1843-1966 (2012)

Authors Index*
(Figures indicate abstract number. *Missing abstracts were withdrawn.

Altavilla A, 66 Lanciotti M, 117

Alvisi MF, 61, 155 Lanzi F, 81, 83
Arrighi N, 52, 53, 54 Larcher A, 7
Ballatore V, 49 Liberati E, 24
Barboro P, 26 Losa A, 3
Bellardita L, 63, 64 Lotrecchiano G, 124
Belotti S, 115 Lucarelli G, 137
Benecchi L, 151, 154, 156, 157 Lughezzani G, 8
Bergamini L, 70 Magnani T, 91
Bernardi A, 20 Mangolini A, 11
Bertaccini A, 188 Marchioro G, 146
Bizzarri C, 77 Marenghi C, 180
Bollito E, 127 Masieri L, 116
Bonetta A, 148 Masini C, 42
Borghesi M, 94, 98 Massari F, 13
Bortolus R, 82 Matei DV, 41, 43
Bosio A, 165 Minervini A, 171, 172, 174, 175
Brausi MA, 1, 2 Mosca A, 129, 130
Bronte G, 145 Napodano G, 132, 143
Bruni A, 106 Nucciotti R, 9, 21
Busetto GM, 30, 31, 33, 35 Oderda M, 103, 149
Capece M, 62 Palmieri F, 51
Capitanio U, 182, 184 Palumbo R, 181
Carchedi M, 162 Passaretti G, 93
Carillo V, 173 Pedrazzoli P, 55
Carmignani L, 144 Perdonà S, 71, 110, 118, 120
Carrara M, 159 Pernetti R, 134
Casadio V, 186 Petrongari MG, 75
Chiara Cecere S, 67 Picozzi S, 135, 138, 139
Colecchia M, 161 Porpiglia F, 73, 74, 133, 136
Costantini A, 57 Rancati T, 158
Cova G, 36, 44 Ricotta R, 104
De Domenico R, 100 Rocca GC, 17, 22
De Nunzio C, 90, 107 Roscigno M, 183
Dell’ Atti L, 4, 6, 10, 5 Ruatta F, 50
Delle Cave A, 125 Saccomanni M, 113
Demichelis F, 84 Sanseverino R, 131, 150
Destefanis P, 69, 163 Saraceni G, 12
Esperto F, 19, 65 Sava T, 25
Fandella A, 177, 178 Schiavina R, 189, 179, 185
Ferrari V, 119 Sciarra A, 27, 28, 29, 45, 46
Ferro M, 56, 60, 105, 153, 160 Serraino D, 80
Fersino Se 114 Serretta V, 59
Fiori C, 140, 167, 168, 170 Signor M, 72
Fratino L, 111 Sorrentino D, 164
Gasparro D, 166 Spagnoletti G, 76, 128, 147, 169
Gatti L, 126 Strada E, 85
Gazzaniga P, 32 Tolento G, 187
Giulianelli R, 37, 38, 39, 40 Traficante A, 108, 109
Gontero P, 101 Trippitelli A, 48
Gravina GL, 14, 15, 16, 87, 89 Tuccio A, 176
Guarneri A, 112 Ventura L, 141, 142
Guercio S, 152 Verri C, 23
Iacovelli R, 68 Volpe A, 78, 79
Introini C, 96, 97, 99 Zarrelli G, 34
La Macchia M, 58

1966