Should Dukes' B patients receive adjuvant therapy? A statistical perspective

Abstract

The benefit of adjuvant therapy, such as 5-fluorouracil(5-FU) combined with leucovorin, is a matter of debate for patients with Dukes'B colon cancer. Several approaches have been taken to address this issue. Initially, studies were conducted to assess treatment benefits in both Dukes'B and Dukes'C patients. These studies identified an overall benefit of adjuvant treatment and enrolled enough Dukes'C patients to determine a treatment benefit for adjuvant 5-FU/leucovorin in this subpopulation. However, the individual studies were insufficiently powered to detect a treatment benefit in Dukes'B patients. An analysis of four separate studies(National Surgical Adjuvant Breast and Bowel project) compared the benefit of adjuvant treatment in Dukes'B patients with that in Dukes'C patients and showed similar relative reductions in mortality and disease-free survival in Dukes'B and in Duke's C patients. The Liver Infusion Meta-Analysis Group also reported similar relative benefits from a portal vein infusion of 5-FU-based chemotherapy in Dukes'B and Dukes'C patients. The International Multicenter Pooled Analysis of Colon Cancer Trials B2 study, which combined data from patients with Dukes'B colon cancer in five separate trials, failed to show a statistically significant benefit of adjuvant 5FU/leucovorin compared with surgery alone. We review the advantages and limitations of different approaches to detect treatment benefits in patients with Dukes'B colon cancer, and we argue that there is a need for a meta-analysis of all adjuvant trials to reliably address this question.