Gynecologic Oncology 132 (2014) 254–259

Contents lists available at ScienceDirect

Gynecologic Oncology
journal homepage: www.elsevier.com/locate/ygyno

Review

Management of low-risk early-stage cervical cancer: Should conization,

simple trachelectomy, or simple hysterectomy replace radical surgery
as the new standard of care?☆
Pedro T. Ramirez a,⁎, Rene Pareja b, Gabriel J. Rendón b, Carlos Millan c,
Michael Frumovitz a, Kathleen M. Schmeler a
a
Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
b
Department of Gynecologic Oncology, Instituto de Cancerología Las Américas, Medellín, Colombia
c
Department of Gynecology, Hospital Quiron, Murcia, Spain

H I G H L I G H T S

• Conservative surgery is feasible in patients with low-risk early-stage cervix cancer.

• Conization, simple trachelectomy, and hysterectomy are safe options for low-risk patients.
• Prospective trials are ongoing evaluating role of conservative surgery: ConCerv, SHAPE, and GOG 278.

a r t i c l e i n f o a b s t r a c t

Article history: The standard treatment for women with early-stage cervical cancer (IA2–IB1) remains radical hysterectomy with
Received 24 June 2013 pelvic lymphadenectomy. In select patients interested in future fertility, the option of radical trachelectomy with
Accepted 7 September 2013 pelvic lymphadenectomy is also considered a viable option. The possibility of less radical surgery may be appropriate
Available online 14 September 2013
not only for patients desiring to preserve fertility but also for all patients with low-risk early-stage cervical cancer.
Recently, a number of studies have explored less radical surgical options for early-stage cervical cancer, including
Keywords:
Cervical cancer
simple hysterectomy, simple trachelectomy, and cervical conization with or without sentinel lymph node biopsy
Conization and pelvic lymph node dissection. Such options may be available for patients with low-risk early-stage cervical
Simple hysterectomy cancer. Criteria that define this low-risk group include: squamous carcinoma, adenocarcinoma, or adenosquamous
Simple trachelectomy carcinoma, tumor size b 2 cm, stromal invasion b 10 mm, and no lymph-vascular space invasion. In this report, we
Conservative provide a review of the existing literature on the conservative management of cervical cancer and describe ongoing
multi-institutional trials evaluating the role of conservative surgery in selected patients with early-stage cervical
cancer.
© 2013 Published by Elsevier Inc.

Contents

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255
Rationale for conservative management of cervical cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255
Data from studies on conservative management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255
Summary of data from retrospective studies of conservative management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 257
Prospective trials of conservative surgical management of low-risk cervical cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258
Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258
Conflict
Conflict ofofinterest
interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258
258
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 258

☆ Financial support: The University of Texas MD Anderson Cancer Center is supported in part by the National Institutes of Health through Cancer Center Support Grant CA016672.
⁎ Corresponding author at: Department of Gynecologic Oncology & Reproductive Medicine, Unit 1362, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd.,
Houston, TX 77030, USA. Fax: +1 713 792 7586.
E-mail address: [email protected] (P.T. Ramirez).

0090-8258/$ – see front matter © 2013 Published by Elsevier Inc.

http://dx.doi.org/10.1016/j.ygyno.2013.09.004
 P.T. Ramirez et al. / Gynecologic Oncology 132 (2014) 254–259 255

Introduction patients (n = 536) with negative lymph nodes, tumor size 2 cm or

smaller, and stromal invasion 10 mm or less was 0.6%.
Cervical cancer is one of the leading causes of cancer and cancer- Wright and colleagues [10] aimed to determine factors predictive of
related deaths among women worldwide, with an estimated 500,000 parametrial tumor spread and to define a subset of patients at low risk
new cases and 275,000 related deaths annually [1]. The standard treat- for parametrial disease. A total of 594 patients with invasive cervical
ment for women diagnosed with early-stage (stage IA2–IB1) cervical cancer who underwent radical hysterectomy were retrospectively
cancer is radical hysterectomy and pelvic lymphadenectomy. However, reviewed. Parametrial metastases were documented in 64 patients
for patients interested in future fertility, an alternative is radical trache- (10.8%). Factors associated with parametrial disease were high-risk
lectomy and pelvic lymphadenectomy [2]. Multiple studies have dem- histology, advanced grade, deep cervical invasion, LVSI, large tumor
onstrated the safety and feasibility of radical trachelectomy [3–5]. In size, advanced stage, uterine or vaginal involvement, and pelvic or
addition, data from retrospective studies have confirmed that oncologic para-aortic lymph node metastases (P b 0.0001 for each). A subgroup
outcomes of radical hysterectomy and radical trachelectomy are equiv- analysis was performed to identify patients at low risk for parametrial
alent [6]. These data have also raised the possibility that less radical spread. They noted that in women with negative lymph nodes, no
surgery may be appropriate not only for patients desiring to preserve LVSI, and tumors smaller than 2 cm, the incidence of parametrial
fertility but for all patients with low-risk early-stage cervical cancer. disease was only 0.4%.
Similar to radical hysterectomy, radical trachelectomy requires Frumovitz et al. [11] conducted a similar study in which the rate of
removal of the parametria and may be associated with significant parametrial involvement was determined in 350 patients who
morbidity. Among the most common side effects are lower urinary underwent a radical hysterectomy. In that study, the overall rate of
tract dysfunction, sexual dysfunction, and colorectal motility disorders parametrial involvement was 7.7%. However, when the authors strati-
associated with autonomic nerve damage [3]. In addition, previous fied for low-risk characteristics, they found that the rate of parametrial
studies have shown that approximately 60% of patients who undergo involvement was zero in the 125 patients who met the following
a radical trachelectomy have no residual disease in their surgical speci- criteria: adenocarcinoma, squamous cell carcinoma, or adenosquamous
men, indicating that perhaps those patients could have been treated carcinoma; tumor size smaller than 2 cm; and no LVSI.
with less radical surgery [7]. The compiled data from these studies demonstrated that in patients
Several studies have explored less radical surgical options for early- with low-risk characteristics, the rate of parametrial involvement was
stage cervical cancer, including simple hysterectomy, simple trachelec- less than 1%. These retrospective findings suggest that perhaps there is
tomy, and cervical conization with or without sentinel lymph node a subset of patients with early-stage cervical cancer who are unneces-
biopsy and pelvic lymph node dissection. In this report, we review the sarily exposed to radical procedures such as radical hysterectomy or
studies published to date on the conservative management of cervical radical trachelectomy.
cancer to determine whether conservative surgery may be appropriate
for patients with low-risk early-stage disease. Studies only published in Data from studies on conservative management
abstract form were not included. We also describe ongoing multi-
institutional studies evaluating the role of conservative surgery in Several small retrospective series have provided initial data suggesting
selected patients with early-stage cervical cancer. the safety and feasibility of a conservative approach in patients with
low-risk early-stage cervical cancer. Here, we review these series in
Rationale for conservative management of cervical cancer chronological order from oldest to newest (Tables 1–3).
One of the earliest studies evaluating the role of conservative
Multiple retrospective studies have shown very low rates of management of low-risk early-stage cervical cancer was published by
parametrial involvement in patients with early-stage cervical cancer Naik et al. [12] in 2007. This was a study of 17 patients with stage IB1
with favorable pathologic characteristics who have undergone radical cervical cancer. Five women underwent a cone biopsy with or without
hysterectomy. These reports suggest that these patients could be laparoscopic pelvic node dissection, and 12 women underwent
managed in a more conservative approach. a laparoscopic-assisted vaginal hysterectomy or total abdominal
An early report by Kinney et al. [8] in 1995, suggested that a subset of hysterectomy with or without pelvic node dissection. There were no
patients at low risk of parametrial spread or disease recurrence might be cases of residual disease in the final surgical specimen. There were
candidates for less radical surgery. The authors evaluated 387 patients also no cases of metastatic disease in the pelvic nodes. With a median
treated for squamous cell carcinoma confined to the cervix. Of these follow-up time of 29 months, there were no documented recurrences.
387 patients, 83 (21.4%) had favorable pathologic characteristics includ- In 2008, Rob et al. [13] published the results of a pilot study to deter-
ing depth of invasion greater than 3 mm but tumor diameter no greater mine the feasibility and safety of using less radical, fertility-preserving
than 2 cm and no lymph-vascular space invasion (LVSI), and no patient surgery in patients with early-stage cervical cancer. In that study, 40 pa-
in this subgroup had parametrial nodal metastases. tients underwent laparoscopic sentinel lymph node identification, with
Subsequently, several other groups published studies on the risk of frozen-section analysis, and if negative, a complete pelvic lymphadenec-
parametrial spread in patients with early-stage cervical cancer. Covens tomy was performed as the first step of the treatment. The inclusion
et al. [9] reported on 842 patients with stage IA1 through IB1 cervical criteria for this study were tumor size b2 cm in largest diameter or
cancer who underwent radical hysterectomy. The goal of the study b50% infiltration of cervical stroma based on magnetic resonance imaging
was to determine the incidence and factors predictive of parametrial in- and ultrasound volumetry. Disease was stage IA1 in 3 patients (all with
volvement and to identify a population at low risk for pathologic LVSI), IA2 in 10 patients (40% with LVSI), and IB1 in 27 patients (38.5%
parametrial involvement. Thirty-three patients (4%) had pathologic with LVSI). Thirty-two patients had squamous cell carcinoma, 7 had ade-
parametrial involvement, eight in the parametrial lymph nodes and 25 nocarcinoma, and 1 had adenosquamous carcinoma. Six frozen sections
in the parametrial tissue (none had both). Compared with patients (15%) were positive, and in these 6 patients, a radical hysterectomy was
without parametrial involvement, those with parametrial involvement performed. The authors noted that 24 of 32 patients whose reproductive
were older (42 vs. 40 years, P b 0.04), had larger tumors (median, 2.2 ability had been maintained tried to conceive. Of these 24 women, 17
vs. 1.8 cm, P b 0.04), had a higher incidence of LVSI (85% vs. 45%, P = (71%) became pregnant. Eleven women gave birth to 12 children; with
0.0004), were more likely to have grade 2 or 3 tumors (95% vs. 65%, three premature deliveries at 24, 34, and 35 weeks; respectively. Nine
P = 0.001), had greater depth of invasion (median, 18 vs. 5 mm, term deliveries were reported.
P b 0.001), and were more likely to have pelvic lymph node metastases In 2009, Pluta et al. [14] published the results of a pilot study to eval-
(44% vs. 5%, P b 0.0001). The incidence of parametrial involvement in uate the feasibility and safety of laparoscopic lymphadenectomy
256 P.T. Ramirez et al. / Gynecologic Oncology 132 (2014) 254–259

Table 1
Patient and tumor characteristics from published studies of conservative surgical treatment for early-stage cervical cancer.

Author (year) N Median age (range), y Histology Stage LVSI

SCC AC Other IA1 + LVSI IA2 IB1 N (%)

Rob [13] 40 28.3a 32 7 1 adsq 3 10 27 17 (42)

Pluta [14] 60 44.6 (33–64) 50 10 0 3 11 46 19 (32)
Maneo [15] 36 31 (24–40) 24 12 0 0 0 36 5 (14)
Fagotti [16] 17 33 (30–43) 12 4 1 glassy 0 4 13 4 (23)
Palaia [17] 14 32 (28–37) 11 3 0 0 5 9 0
Raju [18] 15 28 (20–40)a 9 6 0 0 5 10 0
Biliatis [19] 62 35 (27–67) 49 11 2 adsq 0 0 62 14 (22)
Plante [20] 16 30 (22–44) 10 6 0 4 6 6 4 (25)
Total 260 197 (75.8%) 59 (22.7%) 4 (1.7%) 10 (3.8%) 41 (15.8%) 209 (80.4%)

AC, adenocarcinoma; adsq, adenosquamous carcinoma; glassy, glassy cell carcinoma; LVSI, lymph-vascular space invasion; SCC, squamous cell carcinoma.
a
Mean age.

followed by a simple vaginal hysterectomy in 60 patients with early- pregnant at the time of the report. The remaining 6 pregnancies
stage cervical cancer and negative sentinel lymph nodes. Patients who ended as follows: first-trimester miscarriage (n = 3), second-
did not desire future fertility and had the following favorable pathologic trimester fetal demise (n = 1), ectopic pregnancy (n = 1), and elective
characteristics were included: stage IA1 disease with LVSI or stage IA2 pregnancy termination due to genetic anomaly (n = 1). The authors
or IB1 disease with tumor size less than 2 cm and less than 50% stromal concluded that cervical conization represents a feasible form of conser-
invasion. Fifty patients had squamous cell carcinoma, and 10 patients vative management of stage IB1 cervical cancer and that cervical
had adenocarcinoma. Three patients had stage IA1 disease, 11 had conization is associated with a low risk of relapse.
stage IA2 disease, and 46 had stage IB1 disease. The median age was Also in 2011, Fagotti et al. [16] reported on a series of 17 patients
44.6 years (range, 33–64 years). Five patients (8%) had positive with early-stage cervical cancer (IA2–IB1) who were younger than
sentinel nodes. The median follow-up time was 47 months (range, 45 years and whose tumors measured 2 cm or less. The goal of the
12–92 months). No recurrences were noted in any of the 60 patients study was to explore the role of excisional cone biopsy instead of radical
in the study. trachelectomy as fertility-sparing surgery. All patients had negative pel-
A subsequent study on less radical surgery for cervical cancer was vic lymph nodes on magnetic resonance imaging prior to surgery. All
published by Maneo et al. in 2011 [15]. These authors evaluated the patients underwent laparoscopic pelvic lymphadenectomy and simple
role of simple conization and pelvic lymphadenectomy in patients conization. In case of positive lymph nodes at frozen section or
with stage IB1 disease. A total of 37 patients were scheduled for surgery definitive pathologic analysis, patients were treated with radical hyster-
but one patient was taken to surgery and the procedure abandoned ectomy and pelvic and para-aortic lymphadenectomy.
secondary to grossly enlarged lymph nodes; therefore 36 patients Interestingly, the authors noted that only 17 of 41 patients (41.5%)
were included in the final analysis. The median age was 31 years who met the inclusion criteria were willing to enter the trial. The medi-
(range, 24–40 years), and the median tumor size was 11.7 mm an age was 33 years (range, 30–43 years). The stage was IA2 in 4 pa-
(range, 8–25 mm). Twenty-four patients (67%) had squamous cell tients (24%) and IB1 in 13 patients (76%). The most common
carcinoma, and 12 (33%) had adenocarcinoma. Five patients (14%) had histologic subtype was squamous cell carcinoma, which was seen in
LVSI. All patients had undergone a prior conization, and 8 patients also 12 patients (71%). LVSI was present in 4 patients (23%). The median
underwent a re-conization. All final conization and re-conization speci- nodal count was 18 (range, 11–51). Four patients (23%) required radical
mens were free of margin involvement. The median follow-up time was hysterectomy, 3 for infiltration of the margins and 1 for a positive lymph
66 months (range, 18–168 months). One patient had a recurrence in node. Two patients were treated with adjuvant chemotherapy because
the pelvis 34 months after initial therapy. Twenty-one pregnancies of positive resection margins. After a median follow-up time of
occurred in 17 patients, and 14 live babies were born (3 were born 16 months (range, 8–101 months), no recurrences were observed.
preterm, at 27, 32, and 33 weeks; respectively). One patient was still Five patients tried to conceive. Two of them had spontaneous

Table 2
Surgical procedure in published studies of conservative surgical treatment for early-stage cervical cancer.

Author (year) No. of planned Sentinel lymph Radical Less radical procedures Positive Adjuvant Adjuvant Follow-up time, Relapses Deaths
surgeries node biopsy hysterectomy lymph nodes radiotherapy chemotherapy median (range),
months

Rob [13] 40 Yes 6 Cone biopsy + PLND = 10 6 0 0 47 (12–102) 1 0

Simple trach + PLND = 24
Pluta [14] 60 Yes 3 TH + PLND = 57 5 5 0 47 (12–92) 0 0
Maneo [15] 37 No N/A Cone biopsy + PLND = 36 0 0 0 66 (18–168) 1 1
Fagotti [16] 17 No 4 Cone biopsy + PLND = 13 1 0 2 16 (8–101) 0 0
Palaia [17] 14 No 0 Simple trach + PLND = 14 0 0 0 38 (18–96) 0 0
Raju [18] 15 No 0 Simple trach + PLND = 15 0 0 0 96 (12–120) 0 0
Biliatis [19] 62 No 0 Cone biopsy + PLND = 35a 1 0 0 56 (13–132) 0 0
TH + PLND = 27b
Plante [20] 16 Yes 0 Simple trach + PLND = 16c 0 0 0 27 (1–65) 0 0
Total 261 13 247 13 5 2 2 1

PLND, pelvic lymphadenectomy; TH, total hysterectomy; trach, trachelectomy.

a
No PLND in 4 patients.
b
No PLND in 1 patient.
c
Six patients had sentinel lymph node mapping alone.
 P.T. Ramirez et al. / Gynecologic Oncology 132 (2014) 254–259 257

Table 3
Obstetrical outcomes in published studies of conservative surgical treatment for early-stage cervical cancer.

Author (year) Planned Less radical Attempting to Became Number of Miscarriages Deliveries Patients pregnant
surgeries surgery conceive pregnant pregnancies at time of report
1st term 2nd term Preterm At term

Rob [13] 40 34 24/32 (75%) 17 23 5 3 3 9 3

Maneo [15] 37 36 NR 17 21 5 1 3 11 1
Fagotti [16] 17 13 5/13 (38%) 2 2 0 0 0 2 0
Palaia [17] 14 14 NR 8 8 NR NR NR 3 NR
Raju [18] 15 15 5 4 4 0 0 0 4 0
Biliatis [19] 35 35 NR NR 7 0 0 0 7 0
Plante [20] 16 16 8 8 8 0 0 0 4 4
Total 174a 163a – 56 73 10 4 6 40 8

NR, not reported.

a
The total number of planned surgeries and total number of less radical surgery were recalculated to reflect the fact that all patients in the Pluta study [14] underwent a hysterectomy
and that 27 patients in the Biliatis study [19] also underwent a hysterectomy.

pregnancies, and the remaining 3 underwent in vitro fertilization than 500 mm3 in a loop biopsy specimen. A total of 62 women were
without success. No miscarriages or preterm deliveries were noted. identified with a median age of 35 years (range, 27–67 years). Histologic
The authors concluded that conization and laparoscopic pelvic lymph- subtype was squamous cell carcinoma in 49 patients (79%), adenocarci-
adenectomy are safe and feasible in this low-risk group of patients. noma in 11 patients (17.7%), and adenosquamous carcinoma in 2 pa-
In 2012, Palaia et al. [17] reported on the safety and feasibility of tients (3.3%). Thirty-five women (56%) were treated with loop biopsy,
simple trachelectomy plus pelvic lymphadenectomy in 14 young while 27 (46%) had a simple hysterectomy. Fifty-seven (92%) had pelvic
patients affected by early-stage cervical cancer. Inclusion criteria for lymphadenectomy, and 1 positive node was detected. The median num-
their study were age 38 years or younger, strong desire to maintain ber of lymph nodes removed was 11 (range, 3–25). There were no cases
fertility, stage IB1 or earlier disease, tumor size less than 2 cm, no of residual disease in the definitive treatment specimen. After a median
LVSI, and no evidence of nodal metastasis. All patients underwent a follow-up of 56 months (range, 13–132 months), no recurrences were
laparoscopic bilateral pelvic lymphadenectomy. The lymph nodes noted. In the group of women treated with loop excision, 7 pregnancies
were then analyzed by frozen section. If the pelvic nodes were positive were recorded, and 7 live babies were born. No preterm deliveries or
for disease, standard abdominal radical hysterectomy was performed. In second-trimester miscarriages were noted.
the absence of nodal metastasis at frozen section analysis, a simple A recent publication by Plante et al. in 2013 [20] evaluated the
vaginal trachelectomy was performed. feasibility of simple vaginal trachelectomy and node assessment in 16
The median age was 32 years (range, 28–37 years). Eleven patients patients with low-risk early-stage cervical cancer (b2 cm). All patients
had squamous carcinoma, and 9 patients had stage IB1 disease. The me- underwent a simple vaginal trachelectomy preceded by laparoscopic
dian tumor size was 17 mm (range, 14–19 mm). The median operative sentinel node mapping plus or minus pelvic node dissection. Four pa-
time was 120 min (range, 95–210 min), and the median estimated tients had stage IA1 disease with LVSI, 6 patients had stage IA2 disease,
blood loss was 200 mL (range, 100–400 mL). The median follow-up and 6 patients had stage IB1 disease. Ten patients had squamous cell
time was 38 months (range, 18–96 months). At last follow-up, 13 carcinoma, and 10 patients had grade 1 disease. Only 4 patients had
patients were alive without evidence of disease. One patient died from LVSI. The median operative time was 150 min (range, 120–180 min),
another cause (vesical cancer). No recurrences were observed. Eight and median blood loss was 50 mL (range, 50–150 mL). On final pathol-
patients had become pregnant, and 3 of them had had a term delivery. ogy, lymph nodes were negative in all patients. Thirteen patients (81%)
The authors concluded that patients with low-risk early-stage cervical had either no residual disease (n = 6) or residual dysplasia only (n =
cancer could be safely treated with simple trachelectomy. 7) in the trachelectomy specimen. Margins were negative in all cases.
Also in 2012, Raju et al. [18] evaluated 66 patients who underwent With a median follow-up time of 27 months (range, 1–65 months),
either a simple vaginal trachelectomy (n = 15) with pelvic lymphade- there were no recurrences. Eight patients had conceived: 4 had term de-
nectomy or radical vaginal trachelectomy (n = 51) with pelvic lymph- liveries, and 4 pregnancies were ongoing at the time of publication. The
adenectomy for stage IA2 or IB1 cervical cancer. The criteria for authors concluded that simple trachelectomy and lymph node
performing a simple vaginal trachelectomy were a loop electrosurgical evaluation seems to be a safe alternative in well-selected patients
excision procedure or cone biopsy specimen with tumor-free margins, with low-risk early-stage cervical cancer.
tumor not larger than 1 cm in greatest diameter, no evidence of LVSI,
and tumor grade 1 or 2. Of the 15 patients who underwent simple
vaginal trachelectomy, 5 had stage IA2 disease, and 10 had stage IB1 dis- Summary of data from retrospective studies of
ease. Nine had squamous cell carcinoma, and 6 had adenocarcinoma. No conservative management
patient had LVSI. There was no residual disease in the surgical specimen
in 8 of the 15 patients (53%) who underwent simple vaginal trachelec- To date, 260 women with early-stage cervical cancer managed con-
tomy (compared with 29% of the patients who underwent radical vagi- servatively have been described in the literature (Table 1). Of these
nal trachelectomy). The median follow-up time for the patients who women, 197 (75.8%) had a diagnosis of squamous cell carcinoma, and
underwent simple vaginal trachelectomy was 96 months (range, 12– 59 (22.7%) had a diagnosis of adenocarcinoma. Most women (80.4%)
120 months). No recurrences were observed. Five patients (33%) had stage IB1 disease. The rate of LVSI in patients with a conservative
attempt to conceive, 4 patients (80%) became pregnant, and all 4 of approach ranged from 0 to 42%. The LVSI status is considered a surro-
these patients had a term delivery. The authors concluded that it is pos- gate for lymph node involvement. However, it is important to note
sible to select patients for a less radical fertility-sparing procedure that even with conservative management, all patients routinely under-
through identification of measurable low-risk factors. go sentinel node identification or complete pelvic lymphadenectomy.
Biliatis et al. [19] evaluated survival and obstetrical outcomes follow- Equally, the oncologic outcomes are very favorable as detailed below.
ing conservative management of small-volume stage IB1 cervical cancer. Follow-up time in the series published to date ranged from 1 to
In this series the authors offered an update on the previous publication 168 months. At the time the reports were published, 2 patients had re-
by Naik et al. [12]. Small-volume disease was defined as a tumor less lapsed, and 1 patient had died of recurrent disease (Table 2). A total of
258 P.T. Ramirez et al. / Gynecologic Oncology 132 (2014) 254–259

73 pregnancies have been reported, with 46 deliveries documented and cancer worry, surgical complications, and overall quality of life; and to
8 pregnancies ongoing at the time of publication (Table 3). determine participants' intention for conception, determine the fertility
rate, and assess the reproductive concerns for women following cone
Prospective trials of conservative surgical management of low-risk biopsy and pelvic lymphadenectomy. The eligibility criteria include
cervical cancer histologic diagnosis of squamous cell carcinoma, adenocarcinoma, or
adenosquamous carcinoma of the cervix; stage IA1 (LVSI positive),
Currently, 3 prospective trials are evaluating a conservative IA2, or IB1 disease; tumor size 2 cm or smaller; and any grade. All pa-
approach in patients with low-risk early-stage cervical cancer. tients must have had a cone biopsy or loop electrosurgical excision pro-
The first is a prospective trial lead by Schmeler and colleagues at The cedure with margins negative for carcinoma and high-grade dysplasia.
University of Texas MD Anderson Cancer Center [7]. The trial (ConCerv) Depth of invasion must be no greater than 10 mm. Similarly, patients
is a multi-institutional international trial evaluating the safety and feasi- must have no evidence of metastasis on magnetic resonance imaging
bility of performing conservative surgery in women with early-stage or computed tomography scan of the pelvis and chest imaging. In this
cervical cancer with favorable pathologic characteristics. The inclusion study, patients will be stratified according to their fertility wishes to ei-
criteria are stage IA2 or IB1 disease; tumor size 2 cm or smaller; and ther cone biopsy and pelvic lymphadenectomy or simple hysterectomy
squamous cell carcinoma (any grade) or adenocarcinoma (grades 1 or and pelvic lymphadenectomy. The minimum sample size for this study
2). Patients with high-risk histology or LVSI are excluded. Patients desir- is anticipated to be 200 eligible patients. Depending on results from
ing future fertility undergo only cervical conization and pelvic lymph interim analyses and feasibility assessments, this study may accrue up
node dissection with lymphatic mapping. Patients not desiring future to 600 patients.
fertility undergo a simple hysterectomy and pelvic lymph node dissec-
tion with lymphatic mapping. The primary objective is to evaluate the Conclusion
safety and feasibility of performing conservative surgery in this
group of patients. Secondary objectives include assessing treatment- The current literature demonstrates that patients with low-risk early-
associated morbidity and quality of life compared with historical stage cervical cancer may be ideal candidates for conservative surgery.
outcomes in matched patients treated with radical hysterectomy. In ad- Depending on the patient's interest in future fertility, either cervical
dition, the sensitivity of lymphatic mapping and sentinel lymph node conization or simple hysterectomy with bilateral pelvic lymphadenecto-
biopsy is being estimated. The sample size for the study will be 100 my may be adequate. It is critical to highlight the fact that conservative
patients across all participating institutions. At the time of this writing, surgery for patients with stage IA2–IB1 remains an approach that should
the study had accrued 25 patients from 4 collaborating sites. only be considered in the setting of clinical trials. Equally, it is very
The second ongoing study is a Gynecologic Cancer Intergroup trial important to assure that before embarking on a conservative approach
led by Plante and colleagues. The study is known as the SHAPE Trial all pathology should be carefully reviewed by an expert gynecologic pa-
[21]. This is a randomized trial comparing radical hysterectomy and pel- thologist who will provide accurate information on histologic subtype,
vic node dissection to simple hysterectomy and pelvic node dissection. grade, depth of invasion, margin status, and LVSI status. Lastly, very thor-
The inclusion criteria are stage IA2 or IB1 disease, tumor size smaller ough patient counseling is recommended to assure the patient is aware
than 2 cm, squamous cell carcinoma or adenocarcinoma, and less than of guidelines dictating current standard of care. Ongoing, prospective
10 mm stromal invasion on LEEP/cone biopsy or less than 50% stromal trials will provide more concrete evidence on the role of conservative
invasion on pelvic magnetic resonance imaging. All tumor grades are surgery in these low-risk patients.
allowed, and patients with LVSI are eligible. The exclusion criteria
include high-risk histologic subtype (clear cell carcinoma or small cell
Conflict of interest
carcinoma), stage IA1 disease, evidence of lymph node metastases or
The authors report no conflict of interest.
extrauterine disease, neoadjuvant chemotherapy, pregnancy, and de-
sire to preserve fertility. Patients will be randomized 1:1 to the control
treatment, which is a radical hysterectomy and pelvic lymphadenecto-
Acknowledgments
my with or without sentinel node mapping (as this is optional), or the
experimental treatment, which is a simple hysterectomy with pelvic
The authors wish to thank Ms. Stephanie Deming for her editorial
lymphadenectomy with or without sentinel node mapping. The prima-
contribution to the manuscript.
ry objectives are to determine whether simple hysterectomy in patients
with low-risk cervical cancer is safe and associated with less morbidity
than radical hysterectomy and to determine whether overall survival is References
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