Structured Exercise Lowers Risk of Colon Cancer Recurrence & Death

Advanced colon cancer patients who participated in a structured exercise program following surgery and adjuvant chemotherapy reduced their risk of recurrent or new cancer and increased survival, according to an international, randomized Phase III trial. In the CHALLENGE clinical trial of 889 patients, after a median follow-up of 7.9 years, 93 patients in the structured exercise program had their cancer recur compared to 131 patients who only received health education materials. Structured exercise led to a 28 percent lower risk of recurrent or new cancers after 5 years. Deaths occurred in 41 patients in the structured exercise program and 66 patients in the health education materials group, reflecting a 37 percent lower risk of death. “The CHALLENGE trial sets a new standard of care for colon cancer. Structured exercise after adjuvant chemotherapy improves fitness, disease-free survival (DFS), and overall survival (OS),” said lead author Christopher Booth, MD, FRCPC, a medical oncologist at Queen's University in Kingston, Canada, at a press briefing during the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract LBA3510). “The results demonstrate a first-in-class anti-cancer effect.” Study results were published simultaneously in the New England Journal of Medicine (2025; https://doi.org/10.1056/NEJMoa2502760). Despite standard treatment for colon cancer with surgery followed by 3-6 months of adjuvant chemotherapy, about 30 percent of patients will relapse and die. Many official guidelines recommend a healthy lifestyle, which includes a well-balanced diet and regular exercise. But even with these guidelines, patients usually receive minimal education and little support for incorporating exercise. “Observational data from 2006 suggested patients who exercise have a lower cancer recurrence rate,” Booth said. Study Details CHALLENGE is the first randomized clinical trial to specifically evaluate whether a structured exercise program can reduce the risk of recurrent or new cancer for a subset of patients with colon cancer. Between 2009 and 2023, researchers enrolled 889 participants from six countries with most participants enrolling from Canada and Australia. Median age was 61 years and 51 percent were female. Most of the patients (90%) had Stage III colon cancer and 10 percent had high-risk Stage II colon cancer. All patients had previously received intent-to-cure surgery and adjuvant chemotherapy regimens, mostly FOLFOX (61%) or CAPOX (15%). The patients were randomly assigned to participate in a 3-year structured exercise program (445 patients) or receive health education materials promoting physical activity and healthy nutrition (444 patients). All participants also received standard cancer surveillance and follow-up care. Patients in the structured exercise program worked with a physical activity consultant twice a month for 6 months and participated in moderate-intensity aerobic activities, such as walking, biking, swimming, or working out on an elliptical machine. Most patients walked briskly for 45-60 minutes, three times a week, he said. After 6 months, patients met with their physical activity consultant once a month with additional sessions available for extra support if needed. Key Findings Physical activity, fitness, and physical function improved and were sustained in both groups, but were significantly higher for those in the structured exercise program. The exercise group showed improvements over 3 years in recreational physical activity, predicted VO2 max, and the distance they could walk in 6 minutes. DFS and OS substantially improved with exercise. “For every 16 people, exercise prevented one person from a recurrence,” Booth said. “For every 14 people, exercise prevented one person from dying.” The deaths were driven by lower colon cancer deaths, not cardiovascular or diabetes deaths, he said. The 5-year DFS rate was 80 percent in the structured exercise program and 74 percent in the health education materials group. The 8-year OS rate was 90 percent in the structured exercise program and 83 percent in the health education materials group. The structured exercise program led to more musculoskeletal adverse events, such as muscle strains or bone fractures (19%) compared to the health education group (12%). Ten percent of these adverse events in the structured exercise program were related to their participation in the program. The researchers plan to explore how exercise reduces cancer recurrence by studying blood samples of the patients who participated in the study. Booth concluded, “The magnitude of benefit is comparable to standard medical therapies. This knowledge alone will not change patient behavior or outcomes. Health systems need to invest in behavior support programs.” The trial shows that an exercise intervention empowers patients and is sustainable for health systems, he said. ASCO Expert in gastrointestinal cancers, Pamela Kunz, MD, of Yale School of Medicine, commented, “This is the first randomized Phase III trial in patients with Stage III and high-risk Stage II colon cancer to demonstrate that post-treatment exercise is both achievable and effective in improving DFS. Exercise as an intervention is a no-brainer and should be implemented broadly.” Mark L. Fuerst is a contributing writer.

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