A phase III study has found that a 3-year structured exercise program initiated soon after completion of adjuvant chemotherapy improves disease-free and overall survival, as well as patient-reported physical functioning and health-related fitness, in patients with stage III and high-risk stage II colon cancer. The study is being presented during the 2025 ASCO Annual Meeting (Abstract LBA3510).
According to the World Health Organization, colorectal cancer is the third most common cancer worldwide—accounting for about 10% of all cancer cases—and is the second leading cause of cancer-related deaths globally. This year, it is estimated that 154,270 new cases of colorectal cancer will be diagnosed in the United States alone, and that nearly 53,000 individuals will die of the disease.
“As oncologists, one of the most common questions we get asked by patients is, ‘What else can I do to improve my outcome?’ These results now provide us with a clear answer: an exercise program that includes a personal trainer will reduce the risk of recurrent or new cancer, make you feel better, and help you live longer,” said lead author Christopher Booth, MD, FRCPC, of Queen’s University in Kingston, Canada.
Study Details
The aim of this study was to test the hypothesis that a meaningful increase in recreational physical activity after adjuvant therapy is achievable and will improve disease-free survival in patients with stage III or high-risk stage II colon cancer.
The researchers enrolled 889 patients with resected stage III or high-risk stage II colon cancer from 55 sites in six countries between 2009 and 2024. The patients who had received adjuvant chemotherapy were randomly assigned to a structured exercise program arm (n = 445) or to a health education materials arm (n = 444).
The health education materials contained information promoting physical activity and healthy nutrition in addition to standard surveillance. Participants in the structured exercise program worked with a physical activity consultant who delivered an exercise intervention using behavior-change methodology over 3 years. The goal of the structured exercise program was to increase recreational physical activity by at least 10 MET-hours per week from baseline during the first 6 months—and to sustain that level for 3 years. A MET is a ratio of an individual’s working metabolic rate relative to their resting metabolic rate. Participants chose the type, frequency, intensity, and duration of aerobic exercise in the program.
The primary endpoint of the study was disease-free survival compared by a stratified log-rank test performed on an intention-to-treat basis. Secondary endpoints included overall survival and patient-reported outcomes (SF-36 physical function scale was primary patient-reported outcome).
In the study, 51% of the participants were female, the median age was 61 years, and 90% had stage III disease.
Results
Although patients in both groups saw gains in their physical function, they were significantly higher for patients in the structured exercise program group. The researchers found that compared with health education materials, a structured exercise program resulted in statistically significant improvements in recreational physical activity, predicted VO2max, and 6-minute walk distance, all maintained over the 3-year intervention period.
With a median follow-up of 7.9 years, the study reported 224 disease-free events (93 patients in the structured exercise program arm and 131 patients in the health education materials arm) and 107 deaths (41 patients in the structured exercise program arm and 66 in the health education materials arm) were observed.
The 5-year disease-free survival was 80% in the structured exercise program arm and 74% in the health education materials arm (hazard ratio [HR] = 0.72; 95% confidence interval [CI] = 0.55-0.94; P = .017). Eight-year overall survival was 90% in the structured exercise program arm and 83% in health education materials arm (HR = 0.63; 95% CI = 0.43–0.94; P = .022).
The study results also show that SF-36 physical function was substantially improved in the patients in the structured exercise program arm at 6 months (mean change scores, 7.42 vs 1.10; P < .001), and was sustained for 24 months.
In the safety analysis, 19% of patients (79/428) in the structured exercise program arm reported any grade of musculoskeletal adverse event over the course of the study, compared to 12% of patients (50/433) in the health education materials arm. Ten percent (8/79) of the musculoskeletal adverse events reported on structured exercise program were considered to be related to participation in the physical activity program.
“In patients with stage III and high-risk stage II colon cancer, a 3-year structured exercise program initiated shortly after completion of adjuvant chemotherapy improves disease-free survival, overall-survival, patient-reported physical functioning, and health-related fitness. Health systems should incorporate structured exercise programs as standard-of-care for this patient population,” concluded the study authors.
“This is the first randomized phase III trial in patients with stage III and high-risk stage II colon cancer to demonstrate that posttreatment exercise is both achievable and effective in improving disease-free survival. Exercise as an intervention is a no-brainer and should be implemented broadly,” added Pamela Kunz, MD, of Yale School of Medicine, and an ASCO Expert in gastrointestinal cancers.
Disclosure: This study was funded by the Canadian Cancer Society, the National Health and Medical Research Council, Cancer Research UK, and the University of Sydney Cancer Research Fund. For full disclosures of the study authors, visit coi.asco.org.
