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Do current data support adjuvant treatment for stage II colon cancer?
Must identify patients that will benefit most
This whole subject of whether to treat stage II patients has been an area of much discussion, debate and controversy over the last few years. According to an updated analysis from the MOSAIC trial that Aimery de Gramont presented at last year’s ASCO meeting, there are good data that FOLFOX chemotherapy clearly provides an advantage with respect to disease-free survival in patients who have high-risk, stage II disease. What was interesting to me was, initially, this study suggested benefit for the entire group of stage II patients. Coming out of a more mature analysis, I think the data were compelling. Certainly in the stage II cohort, it did not appear as though a more aggressive therapy of FOLFOX4 was more beneficial over infusion 5-FU/LV alone. Even in that study, 5-FU/LV did have benefit.
The big pro for the QUASAR study was that it was a relatively large study. The majority of the patients enrolled were in fact patients with stage II disease, which is why this study was sufficiently powered. Ninety-one percent of patients had stage II disease, 71% had colon cancer. In this trial, they showed that adjuvant chemotherapy had a survival benefit for patients with stage II disease.
It is not a question of whether we should be treating these patients. Rather, can we identify patients with stage II disease who would optimally benefit from chemotherapy? And, can we identify patients who should be candidates for chemotherapy, but perhaps because of underlying metabolic reasons might be subject to increased toxicity? There is a great deal of ongoing research looking at molecular biochemical predictive markers for efficacy and/or toxicity.
Edward Chu, MD is Professor and Chief of Medical Oncology at the Yale University School of Medicine; Director, Yale Cancer Center, New Haven, Conn.
Decision should be the patient’s
In the studies that have been conducted, it appears that the improvement with whatever chemotherapy — even the standard chemotherapies that are better today than they were 10 years ago — is only incrementally about 1% or 2%. The QUASAR study from the United Kingdom and numerous meta-analyses from the United States show that to be the extent of the treatment effect.
To prove that a therapy improves survival from 80% to 82%, you would need to include thousands of patients. There just is not the will to do that, nor the time. If there is a 0.5% risk of dying from the chemotherapy that is used for colon cancer adjuvant treatment, and the incremental benefit on average across populations is only a couple percent, then the risk:benefit ratio is close. That is the fundamental issue and controversy. If you read position papers, they say that clinicians do not know the right answer and to discuss options with a patient. Patients need to make their own judgment, and it is as much a philosophical judgment as it is a medical judgment.
What is pretty clear is that all stage II colon cancers are not created equal. There is substantial research looking at a variety of molecular features of colon cancer. Researchers have found retrospectively that there are some molecular features that clearly reflect such a favorable prognosis (or an incapacity for the cancer to metastasize) that these patients with tumors with certain features are never going to hear from the colon cancer again, and will never benefit from chemotherapy. This is the kind of lead we need to pursue.
Alan Venook, MD, HemOnc Today’s Gastrointestinal Cancers Section Editor, is Professor of Clinical Medicine at the University of California, San Francisco.