Structured exercise after adjuvant chemotherapy for colon cancer extend overall survival

A structured exercise programme offered alongside health education materials may prolong overall survival (OS) in patients with resected colon cancer who have completed adjuvant chemotherapy, according to the final results of the phase III CHALLENGE trial presented at ASCO 2025.

The risk of disease recurrence, new primary cancer, or death was significantly reduced by 28 percent in patients with stage III or high-risk stage II colon cancer who did the exercise programme and received health education materials after adjuvant treatment vs those who only received education materials (hazard ratio [HR], 0.72, 95 percent confidence interval [CI], 0.55–0.94; p=0.017). [ASCO 2025, abstract LBA3510]

“The disease-free survival (DFS) rate at 5 years for the experimental arm was 80.3 percent vs 73.9 percent in the control arm (absolute difference, 6.4 percentage points), meaning that for every 16 patients who went on the exercise programme, exercise prevented one person from [having a] recurrence or [developing a] new cancer,” said Professor Christopher Booth from the Department of Oncology, Queen’s University at Kingston, Ontario, Canada.

For the trial’s key secondary endpoint of OS, the risk of death was 37-percent lower for patients who enrolled in the structured exercise programme vs those who received health education alone (HR, 0.63, 95 percent CI, 0.43–0.94).

“CHALLENGE sets a new standard of care for the management of stage III and high-risk stage II colon cancer,” said Booth. “Exercise is no longer just an intervention that improves quality of life and fitness; it is a treatment that improves survival for colon cancer and should be made available to all patients.”

Goal of ≥10 MET-hours per week

Patients in the exercise arm received support from a certified physical activity (PA) consultant, such as a kinesiologist, exercise physiologist, or trainer. The structured exercise programme consisted of supervised PA sessions, a personalized PA prescription, as well as counselling sessions on behavioural support over a 3-year period. [N Engl J Med 2025;393:13-25]

The goal of the individualized exercise programme was to increase recreational aerobic exercise by ≥10 metabolic equivalent task (MET)-hours per week from baseline during the first 6 months, and to maintain at least this level afterwards.

Over time, patients randomized to the exercise programme engaged in more recreational moderate-to-vigorous PA than those randomized to receive health education materials alone by an estimated mean of 4.44 MET-hours.

This difference in PA eventually resulted in longer OS in the exercise group, as reflected in the OS rates at 8 years of 90.3 percent vs 83.2 percent (absolute difference, 7.1 percentage points).

“For every 14 people who went on the exercise programme, exercise prevented one person from dying,” said Booth. “This improvement in OS was not driven by a difference in cardiovascular deaths, but by a difference in deaths from colon cancer.”

Knowledge alone likely insufficient

It should be emphasized that patients in the control arm were educated about the benefits of PA from the start.

“Knowledge alone is unlikely to change patient behaviour and outcomes,” wrote the investigators in the published manuscript. “To achieve meaningful increases in exercise will require that health systems invest in behaviour support programmes.”

“Without systems-level changes, PA levels are unlikely to increase,” agreed editorialist Professor Melinda Irwin, a behavioural scientist from the Yale School of Public Health, New Haven, Connecticut, US. [N Engl J Med 2025;393:82-84] “As oncology continues to advance, exercise must become a standard part of care. The time to act is now.”