Exercise Improves Survival End Points After High-Risk CRC Treatment

The implementation of a 3-year structured exercise program after completion of surgery and adjuvant chemotherapy resulted in improved disease-free survival, overall survival, patient-reported physical functioning, and health-related fitness among patients with stage 3 and high-risk stage 3 colorectal cancer (CRC), according to findings from the randomized phase 3 Canadian Cancer Trials Group trial, CO.21 (CHALLENGE).

These findings, which were reported ahead of the 2025 ASCO Annual Meeting, showed that when comparing patients who were randomly assigned to participate in a structured exercise program (445 patients) with those who received health education materials promoting physical activity and healthy nutrition (444 patients), those in the former group had a significantly higher physical function; however, it was noted that both groups sustained improved physical function.

Those assigned to the structured exercise program had improvements which were maintained across recreational physical activity, predicted VO2 max, and distance they could walk in six minutes.

At a median follow-up of 7.9 years, a total of 131 patients in the health education materials group had their cancer recur, compared with 93 patients in the structured exercise program. Moreover, the disease-free survival rate was 74% and 80% in the health education materials and structured exercise program groups at five years, respectively. Additionally, in the structured exercise program, the risk of recurrent or new cancers developing was lowered by 28% versus patients who only received health education materials.

In total, 66 patients in the health education materials group died versus 41 in the structured exercise program. Between these two groups, overall survival was 83% and 90%, respectively, at eight years, lowering the risk of death by 37% for those in the structured exercise program.

“After completing surgery and chemotherapy, about 30% of patients with high-risk stage 2 and stage 3 colon cancer will eventually experience recurrence of their disease. As oncologists, one of the most common questions we get asked by patients is ‘what else can I do to improve my outcome?’” explained lead study author, Dr. Christopher Booth, of Queen’s University in Kingston, Canada. “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.”

Breaking Down the Study Schematics and Safety

The second-leading cause of cancer-related death worldwide is CRC, and in 2025, approximately 106,000 people will be diagnosed with the disease in the United States, according to background provided by the researchers. Although advanced disease typically necessitate surgery to remove tumors followed by chemotherapy to eliminate any remaining cancer cells, CRC recurs in about 30% of these patients. Following recurrence, the disease becomes more difficult to treat and can lead to death.

Moreover, these patients are recommended to follow a healthy lifestyle; however, patients often receive little education or support on how to incorporate a well-balanced diet and regular exercise into their routines, according to the researchers. To address these unmet needs for patients with CRC at an advanced stage, investigators launched the first randomized clinical trial to evaluate if a structured exercise program specifically can lead to a reduction in the risk of recurrent or new cancer within this patient population.

The international CHALLENGE study enrolled 889 participants between 2009 and 2023 at 55 sites from six countries, including Canada and Australia, where the median age of participants enrolled was 61 years, 51% of patients were female, and all patients had previously been treated with intent-to-cure surgery and adjuvant chemotherapy. A majority (90%) of patients enrolled had stage 3 CRC and the rest of patients had high-risk stage 2 CRC.

Eligible patients with resected stage 3 or high-risk stage 2 CRC were randomly assigned to a structured exercise program (445 patients) or to receive health education materials promoting physical activity and healthy nutrition in (444 patients). Both patient groups were given standard cancer surveillance and follow-up care.

Comparatively, those in the structured exercise program worked with a with a physical activity consultant who provided an exercise intervention through behavior change methodology, as well as a an “exercise prescription” for three years. In the first six months, patients met with the consultant twice monthly, but after the six-month mark, patients met with the physical activity consultant once a month and were offered additional sessions for extra support if needed.

The goal for those enrolled on the structured exercise program included an increase in recreational physical activity by at least ten MET-hours/week from baseline during the first six months, and this must be sustained over the course of three years. Additionally, patients on this group were permitted to choose their exercise, as well as the type, frequency, intensity, and duration of it.

The primary end point of the study is disease-free survival versus a stratified log-rank test performed on an intention-to-treat basis, whereas secondary end points included overall survival and patient-reported outcomes.

Regarding safety, 19% (79/428) of patients on the structured exercise program group reported any grade of musculoskeletal adverse side effects, such as muscle strains or bone fractures, whereas 12% (50/433) of those in the health education materials group reported this side effect. Moreover, 10% (8/79) of musculoskeletal side effects in the structured exercise program were considered to be related to their participation in the physical activity program.

Next Steps for Research

“Researchers will explore how exercise reduces cancer recurrence by studying blood samples of the patients who participated in CHALLENGE,” the study authors concluded.

Reference

Booth CM, et al. "A randomized phase III trial of the impact of a structured exercise program on disease–free survival (DFS) in stage 3 or high-risk stage 2 colon cancer: Canadian Cancer Trials Group (CCTG) CO.21 (CHALLENGE)." J Clin Oncol. 2025;43(suppl 17):LBA3510. doi:10.1200/JCO.2025.43.17_suppl.LBA3510.