Adjuvant treatment of stage II colon cancer: is there a true no-chemotherapy group?

In this issue of Annals of Surgical Oncology, Andre et al. present an exhaustive review of the controversial management in the use of adjuvant chemotherapy for stage II colon cancers. The authors review the results of the most recent clinical trials and metaanalyses investigating the value of adjuvant chemotherapy for stage II patients. They emphasize that this is a heterogenous patient population that includes patients with T2, T3, and T4 lesions, tumor perforation, and tumor differentiation, all of whom are believed to be N0. This heterogeneous population is the reason that 5-year survival rates for stage II colon cancer range from a high of 70% to a low of 30%. It is because of this same heterogeneity and the relatively rare event of stage II colon carcinoma that trials attempting to evaluate the treatment efficacy of adjuvant chemotherapy have had insufficient power. Even larger trials that have included both stage II and stage III colon carcinomas have been insufficient to demonstrate a durable benefit in this rare group. It has been estimated, as the authors have pointed out, that to detect a 4% survival benefit at 5 years in stage II colon cancer by using a median of 75% 5-year survival as a baseline would require 4700 patients. The rapid expansion in chemotherapeutic options has made the care of colon cancer patients more complex and optimistic. In the past, when only 5-fluorouracil chemotherapy was an option, there was little enthusiasm for giving chemotherapy in a subset of patients with a 5-year survival rate of 75%. However, now, with a myriad of options, there is considerable enthusiasm for identifying all stages and/or subsets of patients who may receive any form of benefit from additional chemotherapy. To most, this represents an advance in treatment, as has been seen in breast and prostate therapy. The core question remains as to what is a clinically relevant benefit from additional chemotherapy? Is a 5-year increase of 4.3% for stage II colon cancers clinically relevant? If this translates into an improvement of 3 months in overall survival, which is half the duration of the treatment itself (6 months of adjuvant therapy), is it worthwhile in all stage II patients? One of the key areas in which surgery has been lacking has been established surgical criteria for colon resections in cancer. Only until recently has there been a recommendation for at least 12 lymph nodes to be evaluated in all surgically treated colon cancers. This minimum number of lymph nodes retrieved has been demonstrated to improve 5-year survival, through a stage migration effect, and to be highly predictive of survival in both lymph node–negative and lymph node–positive patients. Adequate lymph node identification has been difficult to standardize because of the variability of both surgical technique and pathologic lymph harvest. One technique that may demonstrate the ability to increase lymph node retrieval and possibly improve lymph node stage sensitivity and specificity is sentinel lymph node biopsy. The successful conclusion of this multi-institutional trial of this technique demonstrated the feasibility and possible benefit (Bilchik et al., unpublished data). Received November 29, 2005; accepted December 6, 2005; published online April 13, 2006. Address correspondence and reprint requests to: Robert C. G. Martin, MD; E-mail: robert.martin@louisville.edu.