FAQs - Fast Facts (Stage II Colon Cancer)
Question: What is the standard of care for treatment of stage II colon cancer?
Answer: The standard of care for management of stage II colon cancer is changing rapidly as new data regarding efficacy of various agents and regimens are maturing. Stage II colon cancer comprises tumors classified as T3 (tumor invades through muscularis propira into subserosa or into nonperitonealized pericolic or perirectal tissues) or T4 (tumor directly invades other organs or structures and/or perforates visceral peritoneum) but without nodal involvement (N0) or distant metastasis (M0).1 T3N0M0 is grouped as stage IIA. T4N0M0 is grouped as stage IIB. The current National Comprehensive Cancer Network (NCCN) standard of care for treatment of stage IIA or IIB patients considers the existence of risk factors for recurrence. These risk factors include2:
- Histology grade 3-4
- Lymphatic invasion
- Bowel obstruction at presentation
- Fewer than 12 lymph nodes examined
- T4 extent of disease
- T3 with localized perforation
- T3 with close, indeterminate, or positive surgical margins
For patients with stage IIA disease without risk factors, physicians are encouraged to consider 6 months of treatment with capecitabine monotherapy, fluorouracil (5-FU)/leucovorin (LV)/oxaliplatin (FOLFOX) or 5-FU/LV, whereas for stage IIB disease with risk factors the recommendation for treatment is stronger. In both cases, other suggested options are enrollment in a clinical trial (which is strongly encouraged) and observation.
The caveats to these recommendations, however, build on the 2004 American Society of Clinical Oncology (ASCO) recommendations on adjuvant chemotherapy for stage II colon cancer, which mandate a patient-physician risk-to-benefits discussion3 and maintain that patients with stage II disease should be offered therapy only if they are physically fit, have a reasonable life expectancy, and that they accept the risk of distressing treatment-induced side effects with an understanding of the level of evidence supporting treatment (ie, no statistically significant survival benefit) and the limited 5-year survival benefit (ie, only 5%).2,3
Although this complex question does not have an easy answer, more research that will enable us to help our patients make informed decisions about treatment choices is being reported.
Several years ago, early results of the Multicenter International Study of Oxaliplatin/Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) trial began to emerge. This trial enrolled 2,246 patients with stage II and III colon cancer in a randomized study, with patients receiving 5-FU/LV with or without the addition of oxaliplatin, and at 3 years the results showed improved overall disease-free survival (DFS) (78.2% vs 72.9%) in the oxaliplatin/5-FU/LV (FOLFOX4) arm.4 Additional findings demonstrated a 23% reduction in the risk of recurrence.4 As more information became available, it appeared that this reduction in recurrence held true for stage II as well as stage III patients. Most recently, at the annual ASCO meeting in May 2005, de Gramont and colleagues presented MOSAIC data at 4 years that confirmed that DFS with FOLFOX4 is superior to LV/bolus and infusional 5-FU (LV5FU2). Further analysis of the data showed that patients with high-risk stage II disease had an absolute difference in DFS of 6.6% (76.4% vs 69.8%).5
In a recently closed trial, National Surgical Adjuvant Breast and Bowel Project (NSABP) C-07, the researchers reported early results of a randomized 2-arm study that compared infusional 5-FU/LV with FLOX (same 5-FU/LV regimen with the addition of oxaliplatin 85 mg/m2 as a 2-hour infusion). This study reported that the addition of oxaliplatin to weekly bolus FU/LV significantly prolongs 3-year DFS in patients with stage II and III colon cancer (FLOX 76.5% versus FU/LV 71.6%) and resulted in a 21% reduction in recurrence risk.6
The results of these studies have prompted patients and physicians to rethink treating stage II colon cancer. Previous studies reported that patients with stage II disease already had an 80% 5-year survival, but because it is now recommended that at lease 12 lymph nodes be examined at the time of surgery, it is difficult to evaluate what risk exists for patients with less extensive resection.3
The NCCN recommends that chemotherapy should be considered in stage IIA patients without identified high-risk features. These same guidelines identify high-risk stage II patients (IIB) to include those with T4 lesions, inadequate lymph node sampling (< 12), localized perforation, close surgical margins, poorly differentiated histologic grading, and lymphatic or vascular invasion.2
Even with the additional information acquired from the studies described above, the question of whom to treat remains an individual discussion between physician and patient. A meta-analysis examining whether patients with curatively resected stage II colon cancer should be offered adjuvant chemotherapy as part of routine clinical practice found no evidence of a statistically significant survival benefit in patients with stage II disease receiving adjuvant chemotherapy and that patients who undergo complete resection and adjuvant chemotherapy for stage II disease will see 5-year survival improve by only 5%.3 Based on those findings, it is recommended that treatment options addressing benefit-versus-risk considerations should be thoroughly discussed between the physician and patient. As always, the physician's knowledge of the patient's comorbidities, access to health care, and life expectancy must be considered along with the patient's treatment wishes.2,3
References
- American Joint Committee on Cancer (AJCC). AJCC Cancer Staging Manual, 6th ed. Springer-Verlag: New York; 2002 (or visit www.cancerstaging.net).
- National Comprehensive Cancer Network (NCCN). Clinical practice guidelines in oncology: colon cancer, version 2, 2006. Available at: http://www.nccn.org/professionals/physician_gls/default.asp.
- Benson AB III, Schrag D, Somerfield MR, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol. 2004;22:3408-3419. [ Pub Med ]
- André 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.
- de Gramont A, Boni C, Navarro M, et al. Oxaliplatin/5FU/LV in the adjuvant treatment of stage II and stage III colon cancer: efficacy results with a median follow-up of 4 years. J Clin Oncol. 2005;23(suppl 16):246s. Abstract 3501,
- Wolmark N, Wieand S, Kuebler, JP, et al. A phase III trial comparing FULV to FULV + oxaliplatin in stage II or III carcinoma of the colon: results of NSABP Protocol C-07. J Clin Oncol. 2005;23(suppl 16):246s. Late-breaking abstract 3500.
[ Previous Page ] [ Home ]
This page was last modified on 7/31/2006, at 2:15:28 pm ET.
Web site developed by Meniscus Limited.