CHALLENGE Trial: Exercise After Colon Cancer Chemo

For years, studies have hinted that active colon cancer survivors do better than inactive ones. Those studies could not prove that exercise was the reason. The CHALLENGE trial was built to answer that question properly. Its results came out in the New England Journal of Medicine in 2025, and they landed clearly on the side of exercise.

What the trial tested

CHALLENGE was a randomized phase 3 trial. It enrolled 889 people at 55 centers between 2009 and 2024. Everyone had colon cancer that had been removed by surgery. Everyone had also finished adjuvant chemotherapy, meaning chemotherapy given after surgery to lower the risk of the cancer returning.

Half were assigned to a structured exercise program plus health-education materials. The other half got the health-education materials alone.

The program was not a pamphlet. It was a 3-year plan run with a physical activity consultant. Each person got an individualized activity prescription based on their fitness test results, activity history, and preferences. Most people were expected to choose walking. Support was intensive for the first 6 months, reduced for months 6 to 12, and minimal from months 12 to 36. The goal was to add at least 10 MET-hours of activity per week. A MET-hour is a standard way of measuring how much energy activity uses over time.

Exactly who the results cover

The trial's entry rules were narrow, and they matter.

• The cancer was a completely resected adenocarcinoma of the colon. This was not a rectal cancer trial.
• The disease was stage III, or high-risk stage II. High risk meant a T4 tumor, fewer than 12 sampled lymph nodes, or poorly differentiated cells.
• Participants had received 5-fluorouracil-based adjuvant chemotherapy, with the last dose 60 to 180 days before joining.
• Imaging showed no sign of the cancer having spread or returned, and the CEA blood marker was 5 µg/L or lower.
• Participants were not already meeting activity guidelines of 150 minutes of moderate-to-vigorous activity a week.

So the results describe people who were cancer-free on scans, recently done with chemotherapy, and mostly inactive at the start.

What the trial showed

The primary endpoint was disease-free survival. That clock runs from randomization until the cancer returns, a new colorectal or other cancer appears, or the person dies of any cause.

After a median follow-up of 7.9 years, the exercise group did better. At 5 years, 80.3% of the exercise group were alive and disease free, compared with 73.9% of the health-education group. That is a difference of 6.4 percentage points. The hazard ratio was 0.72, meaning a 28% lower relative risk of recurrence, new cancer, or death.

Overall survival also favored exercise. At 8 years, 90.3% of the exercise group were alive, versus 83.2% of the comparison group. The hazard ratio for death was 0.63.

This is worth pausing on. Many cancer trials show a delay in progression without showing that people live longer. Here, the results supported both: less recurrence and longer life.

What it did not show, and the caveats

The trial does not show that exercise replaces any cancer treatment. Everyone in it had already had surgery and chemotherapy.

It also does not show that advice alone works. The comparison group received health-education materials and still did worse. What was tested was a supported, coached, 3-year program.

And the benefit was a shift in odds, not a guarantee. Most people in both groups did well at 5 years. Some people in the exercise group still relapsed.

Exercise had costs, too. Musculoskeletal adverse events, such as muscle or joint problems, occurred in 18.5% of the exercise group versus 11.5% of the health-education group.

What to raise with the team

• Is there any medical reason I should not start a walking or exercise program now?
• My neuropathy, ostomy, or joint pain worries me. What kind of activity fits my situation?
• Can I be referred to a physical therapist, exercise physiologist, or cancer-exercise program with coaching, since coaching is what the trial tested?
• How does this fit with my follow-up plan of scans and CEA blood tests?
• I had rectal cancer, or a different stage. Does this evidence apply to me?

What this does not mean

• It does not mean exercise treats colon cancer on its own, or that anyone should skip or shorten chemotherapy.
• It does not mean the findings apply to every colorectal cancer. The trial covered resected high-risk stage II and stage III colon cancer after adjuvant chemotherapy.
• It does not mean a gym membership is required. Most participants were expected to choose walking, built up gradually with support.
• It does not mean someone whose cancer returned failed at exercise. The benefit was a change in group-level odds.

Sources

• ClinicalTrials.gov: CHALLENGE trial record and posted results (NCT00819208)
• PubMed: Structured Exercise after Adjuvant Chemotherapy for Colon Cancer, N Engl J Med 2025
• NCI: Physical Activity and Cancer Fact Sheet