Note from the National Guideline Clearinghouse (NGC): The following recommendations address three principal questions identified by the guideline developers.
Should all medically fit patients with curatively resected stage II colon cancer routinely receive adjuvant chemotherapy?
The routine use of adjuvant chemotherapy for medically fit patients with stage II colon cancer is not recommended. Neither the Cancer Care Ontario Practice Guideline Initiative (CCOPGI) systematic review of 37 randomized controlled trials (RCTs) and 11 meta-analyses of adjuvant chemotherapy for colon cancer review, nor the CCOPGI meta-analysis of the 12 American Society of Clinical Oncology (ASCO)-selected RCTs found sufficient supporting evidence for the routine use of adjuvant chemotherapy for these patients. Because clinical trials have not demonstrated a significant improvement in survival, inclusion of a surgery-alone control arm in randomized trials for average-risk stage II patients remains justifiable. At the same time, the oncology research community has recently focused efforts on the conduct of trials to better establish the role of molecular prognostic and predictive factors. The motivation behind these trials is the identification of those patients who are most likely to benefit from treatment by virtue of their high risk of recurrence and/or high probability of response to treatment.
Should patients with curatively resected stage II colon cancer and with identifiable characteristics that predict for a poor prognosis (i.e., high-risk patients) be offered adjuvant chemotherapy?
Direct evidence from randomized controlled trials does not support the use of adjuvant chemotherapy, even for patients with high-risk stage II colon cancer. Patients and oncologists might reasonably be reluctant to choose adjuvant therapy because of this lack of direct evidence of benefit. However, patients and oncologists who are prepared to take the risk of accepting the results from stage III disease as adequate indirect evidence of benefit are justified in considering the use of adjuvant chemotherapy in stage II disease, provided that they understand that the magnitude of benefit as measured in absolute improvement in survival, is small. Patients who have had a complete resection can be reassured that adjuvant treatment for typical stage II disease does not improve 5-year survival by more than an absolute 5%. Whether smaller incremental improvements in survival can be derived from treatment remains open to question.
In either case, the clinical decision should be based on a discussion with the patient about the nature of the direct evidence supporting treatment, the assumptions inherent in accepting indirect evidence of benefit, the anticipated morbidity of treatment, the presence of high-risk prognostic features, and patient preferences. The optimal approach remains to encourage patients with stage II disease who are facing this decision to participate in randomized trials.
What strategies can medical and surgical oncologists use to discuss the issue of adjuvant chemotherapy with their patients in clinical practice?
The Panel emphasizes that the treatment decision-making process in stage II colon cancer must incorporate patient choice. The responsibility of the oncologist is to estimate the risk of recurrence and cancer-related death with and without chemotherapy and to help the patient make an informed decision. Discussion should center on whether the potential benefits of treatment outweigh the potential risks.
Treatment decision making with all stage II patients should include an assessment of other medical problems and anticipated life expectancy. When life expectancy is limited by comorbid illness or very old age, adjuvant treatment offers less potential benefit. To further refine the individual risk for a patient, tools incorporating T and N stage (tumor characteristics) with age and tumor differentiation may also be one way for patients and their physicians to begin discussions about the individual’s risk of recurrence and death. Table 3 in the original guideline document provides a summary of suggested points of discussion between physicians and patients on the value of adjuvant chemotherapy for stage II colon cancer.
