Structured Exercise after Adjuvant Chemotherapy for Colon Cancer
1. The 5-year disease-free survival was 80.3% in the exercise group and 73.9% in the education group, with an overall HR 0.72 (significant).
2. Musculoskeletal adverse events occurred in 18.5% of the exercise group and 11.5% of the education group
Evidence Rating Level: 1 (Excellent)
Study Rundown: Standard adjuvant treatment for high-risk stage II or stage III colorectal cancer still leaves many patients with recurrent disease and quality-of-life impacts. Previous observational and preclinical studies suggested exercise may reduce recurrence risk, but these findings remain inconclusive due to study design limitations. This study was a phase 3 study that compared health education alone to health education plus a structured 3-year exercise program in patients who had completed adjuvant chemotherapy. The primary endpoint was disease-free survival (DFS), and secondary endpoints included overall survival (OS), patient-reported physical functioning, and musculoskeletal adverse events. Median follow-up of 7.9 years. Adherence to the exercise program declined with time, from 83% in the first phase to 63% in the third phase. Those in the exercise group maintained greater improvements over 3 years than the education group in moderate-to-vigorous physical activity (between-group difference range, 5.2-7.4 MET-hours/week), predicted VO₂ max (1.3-2.7 ml/kg/min), and 6-minute walk distance (13-30 m). Patients generally reported larger improvements from baseline physical functioning on surveys (SF-36), with ranging differences between exercise vs education group, 7.1 vs 1.3 at 6 months and 6.1 vs 3.0 at 3 years. The 5-year DFS was 80.3% in the exercise group and 73.9% in the education group, with an overall DFS HR 0.72 (significant). The 8-year OS was 90.3% in the exercise group and 83.2% in the education group, with an overall OS HR 0.63 (significant). Musculoskeletal adverse events occurred in 18.5% in the exercise group (with 10% considered related to the exercise intervention) and in 11.5% in the education group. The strengths of this study included the methodology, and the limitations included changes to standard therapy during recruitment, and possible confounding with increased social connection in the exercise group. Overall, this study found that a 3-year structured exercise program after the completion of adjuvant chemotherapy for colon cancer improved certain outcomes.
Click to read the study in NEJM
In-Depth [randomized controlled trial]: This multicenter phase 3 trial enrolled adults who completed resection and adjuvant therapy for high-risk stage II or stage III colorectal cancer and randomized them (1:1) to receive health-education materials only (education group, n=444) or a structured 3-year exercise program along with education materials (exercise group, n=445). The majority of the population (90%) had stage III disease, and 61% received FOLFOX treatment. Median follow-up of 7.9 years. Adherence to the exercise program declined with time, from 83% in the first phase to 63% in the third phase. Those in the exercise group maintained greater improvements over 3 years than the education group in moderate-to-vigorous physical activity (between-group difference range, 5.2-7.4 MET-hours/week), predicted VO₂ max (1.3-2.7 ml/kg/min), and 6-minute walk distance (13-30 m). Patients generally reported larger improvements from baseline physical functioning on surveys (SF-36), with ranging differences between exercise vs education group, 7.1 vs 1.3 at 6 months and 6.1 vs 3.0 at 3 years. The 5-year DFS was 80.3% in the exercise group and 73.9% in the education group, with an overall DFS HR 0.72 (95%CI, 0.55-0.94, p=0.02). The 8-year OS was 90.3% in the exercise group and 83.2% in the education group, with an overall OS HR 0.63 (95%CI, 0.43-0.94). Musculoskeletal adverse events occurred in 18.5% of the exercise group (with 10% considered related to the exercise intervention) and in 11.5% of the education group. Overall, this study found that a 3-year structured exercise program after the completion of adjuvant chemotherapy for colon cancer improved certain outcomes.
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