Although it is agreed that patients with stage III disease benefit from adjuvant treatment, whether all patients with stage II disease should receive such treatment remains debatable. This controversy was sustained for years by the contradictory conclusions of two large groups of investigators. The National Surgical Adjuvant Breast and Bowel Project concluded that the relative benefits of treatment were largely the same for stage II and stage III tumors,20 whereas the International Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) failed to demonstrate a statistically significant benefit for stage II tumors.21
A recent meta-analysis from the Mayo Clinic,22 which evaluated individual data on 3300 patients who were enrolled in five randomized trials, including those analyzed in IMPACT B2, concluded that patients with stage II disease could benefit from adjuvant chemotherapy, but to a lesser extent than patients with stage III tumors. Indeed, the absolute benefit among patients with stage II disease is only half as great as that among patients with stage III disease, and twice as many patients with stage II tumors are required in such studies in order to detect a difference.
A test for interaction is an appropriate statistical approach to the question of whether the benefit of adjuvant treatment differs between stage II and stage III colorectal cancer.23 In our study, this test showed no significant interaction between the stage of disease and the treatment, indicating that FL plus oxaliplatin benefited both stage II and stage III colorectal cancer. From a clinical standpoint, stage II colon cancer occurs in a heterogeneous, node-negative population in which clinical and biologic prognostic factors other than the status of lymph-node involvement need to be taken into account. Tools are being developed to help physicians assess the risk–benefit ratio of adjuvant chemotherapies for individual patients.22