Stage II colorectal cancer: to treat or not to treat.

The Oncologist 2005;10:332–334 www.TheOncologist. com Correspondence: Patrick G. Johnston, M.D., Ph.D., FRCP, FRCPI, Department of Oncology, Queen’s University Belfast, University Floor, Belfast City Hospital, Belfast BT9 7AB, Northern Ireland. Telephone: 44-28-90-263911; Fax: 44-28-90263744; e-mail: oncology@qub.ac. uk Received March 8, 2005; accepted for publication March 18, 2005. ©AlphaMed Press 1083-7159/2005/$12/00/0 INTRODUCTION Colorectal cancer (CRC) accounts for 10%–15% of all cancers and is the leading cause of cancer deaths in the Western world. Up to 40%–50% of patients who undergo potentially curative surgery alone ultimately relapse and die of metastatic disease [1]. The most important prognostic indicator for survival in colon cancer is tumor stage, which is determined by the depth of penetration through the bowel wall and the number of lymph nodes involved. Over the last 15 years, the development of adjuvant chemotherapy given after surgical removal of tumors for patients with stage II and stage III disease has been used to reduce the risk of recurrence of cancer that may result from remaining tumor cells not detectable after surgery. Many thousands of patients with CRC have been included in clinical trials to assess the potential benefit of various combinations of chemotherapeutic agents. Since the National Institutes of Health 1990 consensus conference, the administration of adjuvant 5-fluorouracil (FU)–based therapy for all medical patients with stage III colorectal cancer has become standard of care and has resulted in a 30%–40% decrease in relapse and mortality rates versus treatment with surgery alone [2]. At the time, the panel did not recommend adjuvant therapy for stage II CRC patients outside the realm of clinical trials, as the data at that time did not support adjuvant therapy for stage II disease. However, one of the problems in the analysis of stage II disease has been the requirement for very large numbers of patients due to the overall favorable prognosis for this subgroup of patients. In adjuvant CRC studies, most clinical trials have included patients with both stage II and stage III disease, and most of those trials have been insufficiently powered to detect any treatment benefit in stage II patients. In stage II CRC, there is tumor penetration through the bowel wall involving the serosa; however, there is no involvement of regional lymph nodes or distant metastases. While the overall survival in this subgroup of patients is approximately 70%–80% 5 years after surgery, in high-risk stage II disease, the clinical outcome is similar to that of patients with stage III disease. Currently, these high-risk patients are identified by tumors that not only penetrate the bowel wall but also show evidence of adhesion to or invasion of surrounding structures, free perforation, obstruction, or aneuploidy. More importantly, recent data, using molecular markers such as loss of heterozygosity (LOH) of 18q or the presence of microsatellite stable tumors, have helped to identify a subgroup of patients with both stage II and stage III CRC who may have much worse prognoses and in whom the administration of chemotherapy may be beneficial