This article appears in the following Annals of Oncology issue: ESMO Clinical Recommendations [View the issue table of contents]
ESMO clinical recommendations |
Primary colon cancer: ESMO Clinical Recommendations for diagnosis, adjuvant treatment and follow-up
1 Digestive Oncology Unit, University Hospital Gasthuisberg, Leuven, Belgium
2 Service of Medical Oncology, Portuguese Institute of Oncology, Lisbon, Portugal
* Correspondence to: ESMO Guidelines Working Group, ESMO Head Office, Via L. Taddei 4, CH-6962 Viganello-Lugano, Switzerland; E-mail: clinicalrecommendations{at}esmo.org
 |
incidence |
|---|
 Top incidence diagnosisstaging and risk assessmentprognosistreatmentfollow-upnotereferences |
|---|
In 2006 there were 412 900 new cases of colorectal cancer in Europe. This is 12.9% of all cancer cases. Colorectal cancer was responsible for 217 400 deaths in Europe in 2006. This represents 12.2% of all cancer deaths.
|
diagnosis |
|---|
|
Topincidencediagnosisstaging and risk assessmentprognosistreatmentfollow-upnotereferences |
|---|
The diagnosis of a colonic adenocarcinoma requires a histopathologic confirmation taken via colonoscopy/sigmoidoscopy. Risk factors including familial and/or hereditary predisposition, location, and histological evaluation of colonic tumors should be documented.
|
staging and risk assessment |
|---|
|
Topincidencediagnosisstaging and risk assessmentprognosistreatmentfollow-upnotereferences |
|---|
Staging provides essential prognostic information relevant for choosing adequate therapy and should also identify patients with resectable distant metastases.
Preoperative staging consists of clinical examination, blood counts, liver and renal function tests, carcino-embryonic antigen (CEA), chest X-ray or preferably chest CT-scan, CT scan of the abdomen including the pelvis and a colonoscopy of the entire large bowel, i.e. with postoperative repeat colonoscopy if proximal parts of the colon were not accessible preoperatively.
Pathologic staging should be done according to the 2002-TNM system with optional listing of the modified Dukes stage, as described in Table 1.
|
Risk factors for colorectal cancer are: family history, familial adenomatous polyposis (FAP) and attenuated FAP (AFAP) syndromes, hereditary non-polyposis colorectal cancer (HNPCC) syndrome, past history of colorectal cancer or adenoma, chronic ulcerative colitis and Crohn's disease.
|
prognosis |
|---|
|
Topincidencediagnosisstaging and risk assessmentprognosistreatmentfollow-upnotereferences |
|---|
Survival rates have been published from the SEER US national cancer registry from January 1, 1991 through December 31, 2000 based on data from 199 363 patients according to the new AJCC sixth edition staging. Overall 5-year colon cancer-specific survival for this entire cohort was 65.2 %. Five-year colon cancer-specific survival by stage was 93.2% for stage I, 84.7% for stage IIa, 72.2% for stage IIb, 83.4% for stage IIIa, 64.1% for stage IIIb, 44.3% for stage IIIc and 8.1% for stage IV cancer. Another large analysis based on the US National Cancer database showed in 50 042 patients from 1987 till 1993 a 5-year survival rate of 59.8% for stage IIIa, 42.0% for stage IIIb and 27.3% for stage IIIc colon cancer.
|
treatment |
|---|
|
Topincidencediagnosisstaging and risk assessmentprognosistreatmentfollow-upnotereferences |
|---|
Surgery is the mainstay in the management of patients with colon cancer. The primary goal is a wide resection of the primary tumor with all locoregional lymph nodes. Optimal surgery by experienced colorectal surgeons should be performed. An adequate number of lymph nodes should be recovered (at least 12) and resection margins have to be free. Laparoscopic resection gives similar oncologic outcome compared to laparotomy and has less postoperative morbidity in experienced surgical hands.
Adjuvant chemotherapy is recommended for stages T1-4, N1-2, M0 (i.e. stage III, modified Dukes C1-3). In stage III colon cancer adjuvant chemotherapy significantly improves the disease-free survival (DFS) and overall survival [I, A]; the absolute survival benefit is approximately 15%. Adjuvant chemotherapy can be considered in selected node-negative patients, especially if high risk factors for recurrence are found. The UK Quasar study that randomized patients postoperatively between no treatment and adjuvant 5-fluorouracil (5-FU) based therapy (mainly with leucovorin) has shown a small but statistically significant improvement in 5-year survival in unselected patients (mainly stage II).
Subgroup analyses of the stage II patients in the randomized studies comparing 5-FU/LV and 5-FU/LV/oxaliplatin (FOLFOX) suggests also an improved DFS in patients with high risk stage II colon cancer. Amongst the known high risk factors in stage II colon cancer are: T4, poorly differentiated adenocarcinoma/undifferentiated carcinoma, vascular invasion, lymphatic vessel invasion, perineural invasion, obstruction or tumour perforation at initial presentation, 
12 regional lymph nodes examined and high CEA level [II, B].
Recent evidence also showed the possible deleterious effect of 5-FU based chemotherapy in stage II tumours with microsatellite instability (MSI). It is therefore important to determine the MSI status in stage II colon cancer. Patients with low risk stage II colon cancer should not be offered adjuvant chemotherapy.
Standard adjuvant treatment consists of fluoropyrimidine-based chemotherapy which has shown a statistically significant survival benefit [I, A].
Options for adjuvant treatment include infusional 5-fluorouracil (5-FU)/LV-regimens without or with oxaliplatin and capecitabine with and without oxaliplatin. Capecitabine has been shown to be at least as effective and less toxic as bolus 5-FU/LV [I, A].
The combination of 5-FU/LV plus oxaliplatin significantly improves the DFS in high risk stage II and III colon cancer and improves also the overall survival in stage III colon cancer compared to 5-FU/LV [I].
The combination of a fluoropyrimidine plus oxaliplatin has therefore become the standard adjuvant treatment for stage III colon cancer in patients fit for combination chemotherapy [A]. The recommended duration of adjuvant chemotherapy is 6 months, starting as soon as the patent is recovered from the surgery and optimally within 6 weeks after the surgical intervention.
The adjuvant treatment after complete resection of metastatic disease is a specific situation addressed in ESMO clinical recommendations on advanced colorectal cancer.
A good correlation has been shown between the 3-year DFS and 5-year survival in the adjuvant treatment of colon cancer. Three-year DFS is therefore now considered as an appropriate endpoint in the adjuvant treatment of colon cancer [III].
|
follow-up |
|---|
|
Topincidencediagnosisstaging and risk assessmentprognosistreatmentfollow-upnotereferences |
|---|
There is no strong proof that regular follow-up after successful treatment improves the outcome of patients with colorectal cancer.
However, it may be clinically beneficial to identify recurrence of colon cancer in a stage at which its diagnosis will have therapeutic implications (i.e. surgery for metastatic disease or for local recurrence).
In the absence of an evidence-based standard, a provisional recommendation to identify patients in need of salvage surgery and to prevent second colorectal cancers is the following:
- History and physical examination and CEA determination (if initially elevated) every 3–6 months for 3 years and every 6–12 months year 4 and 5 after surgery. Colonoscopy at year 1 and thereafter every 3 years to look for metachronous adenomas and cancers.
- CT scan of the chest and abdomen every 6 months for 3 years can be considered in patients who are higher risk for recurrence.
- Other laboratory and radiological examinations are of unproven benefit and shall be restricted to patients with suspicious symptoms.
|
note |
|---|
|
Topincidencediagnosisstaging and risk assessmentprognosistreatmentfollow-upnotereferences |
|---|
Levels of evidence [I–V] and grades of recommendation [A–D] as used by the American Society of Clinical Oncology are given in square brackets. Statements without grading were considered justified standard clinical practice by the experts and the ESMO faculty.
|
footnotes |
|---|
Approved by the ESMO Guidelines Working Group: April 2002, last update November 2008. This publication supercedes the previously published version—Ann Oncol 2008; 19 (Suppl 2): ii29–ii30.
Conflict of interest: Prof. Van Cutsem has reported that he receives research funding from Roche and Sanofi-Aventis. Dr Oliveira has not reported any conflicts of interest.
|
references |
|---|
|
Topincidencediagnosisstaging and risk assessmentprognosistreatmentfollow-upnotereferences |
|---|
1. Ferlay J, Autier P, Moniol M, et al. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol (2007) 18:581–592.
2. O'Connell J, Maggard M, Ko C. Colon cancer survival rates with the new American Joint Committee on Cancer Sixth Edition Staging. J Natl Cancer Inst (2004) 96:1420–1425.
3. Greene F, Stewart A, Norton H. A new TNM staging strategy for node-positive (stage III) colon cancer: an analysis of 50042 patients. Ann Surg (2003) 236:416–421.[CrossRef][Web of Science]
4. Moertel CG, Fleming TR, Macdonald JS, et al. Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Ann Intern Med (1995) 122:321–326.
5. Andre T, Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluorouracil and leucovorin as adjuvant treatment for colon cancer. N Engl J Med (2004) 350:2343–2351.
6. Benson A, Schrag D, Somerfield M, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol (2004) 22:1–12.
7. Twelves C, Wong A, Nowacki M, et al. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med (2005) 352:2696–2704.
8. Van Cutsem E, Tejpar S, Verslype C, Laurent S. Challenges in the adjuvant treatment for patients with stages II and III colon cancer. ASCO Educational Book (2006) 179–186.
9. Quasar Collaborative Group. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet (2007) 370:2020–2029.[CrossRef][Web of Science][Medline]
10. Sargent DJ, Patiyil S, Yothers G, et al. End points for colon cancer adjuvant trials: observations and recommendations based on individual patient data from 20 898 patients enrolled onto 18 randomized trials from the ACCENT Group. J Clin Oncol (2007) 25:4569–4574.
11. Pfister D, Benson A, Somerfield M. Surveillance strategies after curative treatment of colorectal cancer. New Engl J Med (2004) 350:2375–2382.
12. Desch C, Benson A, Somerfield M, et al. Colorectal cancer surveillance: 2005 update of an American Society of Clinical Oncology Practise Guideline. In: J Clin Oncol (2005) 23:8512–8519.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||