18th Facharztseminar

October 27, 2023

Colorectal Cancer

Prof. Dr. med. Carsten T. Viehl

Department of Surgery
Spitalzentrum Biel
[email protected]
Of special importance - for the exam J

«Breaking» news
Epidemiology

• Women: 1. Breast cancer

2. Colorectal cancer (CRC)
3. Lung cancer
• Men: 1. Prostate cancer
2. Lung cancer
3. Colorectal cancer (CRC)

• Incidence: 4,000 new CRC/y in CH

• 55% longterm survivors
Risk factors

• Age
• Nutritional and environmental factors

• Positive family history

• Positive (personal) history of polyps and/or CRC

• Genetic CRC, i.e. FAP and HNPCC

• Inflammatory bowel disease (IBD)
Adenoma-Carcinoma-Sequence:
Development over 5-10 y

Modell according to Kinzler and Vogelstein

Positive effect of screening coloscopy (and FIT):
when to start and when to stop screening?

Pietge H et al. SMF 2017; 17: 943-52

Breekveldt ECH et al. Lancet Gastroenterol Hepatol 2022; 7: 60-68
Positive effect of screening coloscopy –
if invited persons effectively undergo coloscopy

Bretthauer M et al. NEJM 2022; 387: 1547-56

Early onset colorectal cancer (EOCC)

• EOCC (pts < 50 y of age) = 10% of new cases of CRC

• Incidence increasing since 1988
• More often in the left colon
• More often diagnosed in a more advanced stage
• RF: Western-style diet à alteration of gut microbiom
• Genetic background in 1/6 pts. (50% MMR)
• The American Cancer Society recommends CRC
screening between 45 and 75 years of age!
• NB: Switzerland 50-69 y, not yet everywhere!
Wolf AMD et al. CA Cancer J Clin 2018; 68: 250
Sinicrope FA. N Engl J Med 2022; 386: 1547-58
Preop work-up (diagnosis and staging) –
“The big five”

• Complete (!) colonoscopy

• NB: completion colonoscopy 3 mts postop
• Biopsy
• Thoracoabdominal CT scan
• CEA
• Family history

• Rectal cancer: (Endorectal US and/or) pelvic MRI

• Recurrence, liver mets: PET-CT
TNM classification (UICC, 7th edition):

Sobin LH et al. TNM Classification of malignant tumors 7th edition.

Wiley Blackwell, Oxford, 2009
TNM classification (UICC, 8th edition):

Splitting of M stage:
• M1a = Unilocular met(s), e.g. liver or lung
• M1b = Multilocular met(s), e.g. liver and lung
• M1c = Peritoneal carcinomatosis ± other met(s)
• Stage IVa, IVb, IVc accordingly

James D. Brierley et al. TNM Classification of malignant tumours 8th edition.

Wiley-Blackwell, Oxford, 2016
Bowel prep: quo vadis?

• From: mandatory mechanical bowel prep (MBP) or

MBP + antibiotics (AB; Nichols’prep)
• Over: nil
• To: ??
• pRCT MECCLANT-C and -R: ±MBP ±AB (ESCP)
• EvaCol (CH)

Güenaga KF et al. Cochrane Database Syst Rev. 2011: CD001544

Kiran RP et al. Ann Surg 2015; 262: 416
Koller SE et al. Ann Surg 2018; 267: 734
Intraoperative Staging

• Laparotomy or laparoscopy
• Abdominal revision: peritoneal carcinomatosis?
ascites?
liver mets?
• Frozen section, if indicated

• Local resectability? Need for multivisceral resection?

• Defunctioning stoma and neoadjuvant tx?

S3-Leitlinien Kolorektales Karzinom 2014, AWMF-Registernr: 021/007OL

Surgical-oncological principles
(for colon and rectum cancer)

• En bloc resection of tumor and regional lymph nodes

• Ligation of vessels at origin (medial-to-lateral approach)
• R0 resection
• Multivisceral resection, if indicated
• Respecting embryologic layers
• No tears on tumor and meso
• Complete lymphadenectomy
• Anastomosis with good blood supply and without tension
Adapted from Prof. D. Oertli, Basel, with permission
Right hemicolectomy
Left hemicolectomy

From Buhr HJ and Ritz JP. In: Siewert JR et al. Onkologische Chirurgie.
Springer, Heidelberg 2006
What is defining the extended (right or left)
hemicolectomy?

From Buhr HJ and Ritz JP. In: Siewert JR et al. Onkologische Chirurgie.
Springer, Heidelberg 2006
Respecting layers created during embryologic
development

• Intact fascia over mesocolon or mesorectum

• Complete mesocolic excision (CME) for colon cancer (CC)

• Dissection between fascia mesocolica visceralis and
Gerota’s fascia or the duodenal-pancreatic complex
• Total mesorectal excision (TME) for rectal cancer (RC)
• Dissection between fascia recti propria and Waldeyer‘s
or Denonvillier‘s fascia, respectively

Hohenberger W et al. Colorectal Dis 2009;11: 354-64

Heald RJ and Ryall RD. Lancet 1986; 1(8496): 1479-82
Complete mesocolic excision (CME) ± D3-LND

• Recommended in the S3 guidelines, but still a matter of

debate
• Population-based study by the Danish Colorectal Cancer
Group:
• Significant better DFS (particularly stage I+II)
• OS not different
• Significantly more intraop lesions, esp. VMS (1.7%)
• Prospective study:
• CME as an independent factor for better DFS
S3-Leitlinien Kolorektales Karzinom 2014, AWMF-Registernr: 021/007OL
Bertelsen CA et al. Lancet Oncol 2015; 16: 161-8 and Br J Surg 2016; 103: 581
Galizia G et al. Colorectal Dis 2014; 29: 89-97
Importance of regional lymph nodes

• Most important prognostic factor

• pN0 vs. pN+
• pN1 vs. pN2
• Number of (resected and analyzed) lymph nodes
• Intensity of analysis (detection of MM or ITC)

• Most important factor during decision making for or

against adjuvant therapy
Number of (resected and analyzed) lymph nodes

• The higher the number, the better the analysis (and the
prognosis)
• Consensus: at least 12 lymph nodes
• Shared quality criterion of surgeon and pathologist
• Reality:

SEER SAKK 40/00 CH MCT SLN

Country USA CH CH
# LK median 9 16 24

Chen SL et al. Ann Surg 2006; 244: 602

Maurer CA et al. Int J Colorectal Dis 2017; 32: 57
Viehl CT et al. Ann Surg Oncol 2012; 19: 1959
Specifics for rectal cancer (in addition to the
aforementioned principles for CRC)

• Preop work-up
• Rigid proctoscopy (and MRI) →
distance from anal verge
• Local staging (ERUS, MRI)
• Test sphincter function!
HSM
Endorectal ultrasound (ERUS)
MRI with measurements according to HSM

Muscularis propria
Circumferential resection margin (CRM)

• Intact (mesorectal) specimen

• Specific pathological work-up
• CRM must be described by pathologist
(and by radiologist)!
• Prognostic value of CRM

Quirke P et al. Lancet 1986, 2(8514): 996-9

Neoadjuvant therapy for locally advanced RC

• Indication: c/uT3/4 and/or c/uN+ RC

• (Long course) radio-chemotherapy
Radiotherapy 50.4 Gy (28x1.8 Gy) = 5.5 wks
Capecitabine 3-0-3 Wo 1-6
Resection 6-8-10-12 wks later
• Short course radiotherapy (revival with TNT)
Radiotherapy 5x5 Gy = 1 wk; resection during the following week
• Total neoadjuvant tx (TNT) for locally advanced RC
• Watch & wait strategy for ycT0 ycN0
• PD1-blockade for MSI, locally advanced RC

Sauer R et al. NEJM 2004; 351: 1731. Petrelli F et al. Ann Surg 2016; 263: 458
Kapiteijn E et al. NEJM 2001; 345: 638. Hospers G. ASCO 2020, # 4006.
van der Valk MJM. Lancet 2018; 391: 2537. Cercek A. NEJM 2022; 386: 2363
Neoadjuvant therapy for locally advanced RC

• Advantages:
• Improved local control, but no survival improvement
• More often full therapy
• Downsizing possible → restorative surgery ↑
• Disadvantages:
• Overtreatment in case of preop overstaging
• Surgery in irradiated field
• NB: 5-FU vs. FOLFOX

Sauer R et al. NEJM 2004; 351: 1731-40

Kapiteijn E et al. NEJM 2001; 345: 638-46
Total neoadjuvant therapy (TNT)

• Rectal cancer cT4 and/or cN2 and/or + mCRM (RAPIDO)

• RTx 5x5 Gy (1 wk + 2 wk interval)
• Followed by intensive CTx with FOLFOX or CAPOX
(18 wk + 2 wk interval to surgery)
• Tx failure 30% à 24%; pCR 14% à 28%
• However: significant higher LRR @ 5y
• Rectal cancer cT3 or cT4 (PRODIGE23)
• Intensive CTx with FOLFIRINOX x6
• RTx 50.4 Gy + concomitant Capacitabine
• Adjuvant CTx with FOLFOX or CAPOX for 3 mts
• DFS HR 0.69, p=0.034; pCR 12% à 28%

Bahadoer RR et al. Lancet Oncol 2021; 22: 29-42

Dijkstra EA et al. Ann Surg 2023; 278: e766–e772
Conroy T et al. Lancet Oncol 2021; 22: 702–15
Prä: cT3 cN1
Post: ypT3 ypN1 (1/24), downsizing!
Resection techniques for RC

• Local excision
• High anterior resection (HAR) with partial mesorectal
excision (PME)
• Low anterior resection (LAR) with total mesorectal HSM
excision (TME) ± transanal (ta)TME
• Very low anterior resection (VLAR) with TME ±
intersphincteric resection
• Abdominoperineal resection (APR)
Low anterior resection with TME

• Standard for low- to midrectal cancers

• Entire mesorectum („total ME”)
• Intact fascia („complete TME“)

• Distal resection margins:

• HAR+PME: 5 cm
• LAR+TME: ≥ 1 cm
• VLAR+TME: R0

Heald RJ and Ryall RD. Lancet 1986; 1(8496): 1479-82

Nelson H et al. JNCI 2001; 93: 583-96
Rectal replacement

• Colon-J-pouch has better functional outcome than straight

anastomosis for the first 18 mts
• Side-to-end anastomosis (and coloplasty) have similar
outcomes to J-pouch
• However: SAKK 40/04 did not find any statistically or
clinically significant differences after 6 and 12 mts
• Ask pts during follow-up concerning
• low anterior resection syndrom (LARS)!
• sexual and/or bladder dysfunction
Hüttner FJ et al. BJS 2015; 102: 735
Marti WR et al. 2019; 26: 3568
Laparoscopic (or robotic) resection for colon cancer

• Several pRCT with short- and longterm results

• Barcelona trial superior for CRS
• Hongkong trial no difference
• COST trial not inferior
• MRC-CLASSICC trial as effective
• COLOR trial possible worse DFS at 3y
• Metaanalysis oncologically safe
→ Laparoscopic resection for colon cancer: YES

Lacy AM et al. Ann Surg 2008; 248: 1. Leung KL et al. Lancet 2004 ;363: 1187.
Fleshman J et al. Ann Surg 2007; 246: 655. Jayne DG et al. JCO 2007;25: 3061.
Bonjer HJ et al. Lancet Oncol 2009; 10: 44. Bonjer HJ. Arch Surg 2007;142:298
Laparoscopic (or robotic) resection for rectal
cancer

Surrogate marker Local recurrence Survival

MRC-CLASSICC = = =
• LAR R1↑
COLOR II = = =
• Low RC R1↓ ↓
• Stage III DFS↑
ACOSOG Z6051 R1↑ = @ 2y DFS = @ 2y
ALaCaRT R1↑ = =
COREAN n/a = =

= means non-inferior (for non-inferiority trials)

→ Laparoscopic resection for rectal cancer: YES and NO
Jayne DG et al. JCO 2007; 25: 3061. H.J. Bonjer et al. NEJM 2015; 372: 1324.
Fleshman J et al. Ann Surg 2019; 249: 589. Stevenson ARL et al. Ann Surg
2019; 269: 596. Jeong SY et al. Lancet Oncol 2014: 15: 767.
Complications → informed consent!

• Lesions of ureter, spleen, small bowel etc.

• Nerve lesions with sexual and bladder dysfunction
• Wound infects, intraabdominal abscesses
• Anastomotic leakage
• Adhesions
• ∑ 20%

Marusch F et al. Chirurg 2002; 73: 138–146

Goals of structured surveillance

• Early diagnosis of resectable

• syn- and metachronous tumors (polyps and cancer)
• local recurrences
• metastases
• Longer survival with good QoL
• (Psychological) support

Ochsner A, Zuber M and Viehl CT. Ther Umschau 2012; 69: 49 – 55

Prerequisites for structured surveillance according
to SGG schedule

• Stage I-III pts. fit for redo surgery and/or resection of mets
• Interdisciplinary task that should be coordinated by one
person/institution
• Complete preop work-up
(complete colonoscopy and thoracoabdominal CT scan)

• Do not use for high-risk situations (FAP, HNPCC, IBD)

www.sggssg.ch
SGG surveillance schedule 2022 for colo-rectal
cancer

• Surveillance schedule after polypectomy and after

resection of CRC in the same document
• Generally, less surveillance items than in the 2014
version
• Stage- and situation-adapted
• 3 different schedules for CC
• 1 schedule for RC
• Additional schedule for RC with cCR à W&W

www.sggssg.ch
Truniger K et al. SMF 2022; 22: 349–355
SGG surveillance schedule 2022 for colo-rectal
cancer
Compliance with surveillance schedule

• CEA 33%
• CT scans 32% better for pts with adj CTx
• Colonoscopies 24%
• No surveillance at all 13%

• Personalized follow-up card

• Patient involvement and empowerment
• Improved compliance 65-80%

Viehl CT and Ochsner A et al. Ann Surg Oncol 2010; 17: 2663–2669
Rueff J, Viehl CT et al. J Surg Oncol 2020; 122: 529–537
Kraft E et al. SAEZ 2018;99(7):198
Summary

• Complete preop work-up

• Surgical-oncological principles including adequate
lymphadenectomy for CC and for RC
• Specifics for rectal cancer
• Laparoscopic (or robitic) surgery for CRC
• Structured surveillance!
Which statement is not correct?

a) A positive FIT has to be confirmed by a second,

independent FIT.
b) Screening coloscopies lower the risk of CRC.
c) Patient involvement improves adherence to surveillance
guidelines.
d) An extended hemicolectomy is defined by the ligation of
the middle colic artery at its origin.
Which statement is specific for rectal cancer
(as compared to colon cancer)?

a) The resection technique respects the embryologic

layers.
b) A complete lymphadenectomy is performed.
c) The surveillance schedule after resection is independent
of the stage of the disease.
d) Complete pre-op work-up is mandatory.