— “New standard” in operable colon cancer as 3-year program cuts risk of disease recurrence, death

by Mike Bassett, Staff Writer, MedPage Today
June 1, 2025

CHICAGO — A structured exercise program improved survival outcomes in patients on adjuvant chemotherapy for colon cancer, according to the randomized CHALLENGE study.

The phase III trial showed that 5-year disease-free survival (DFS) was 80.3% with the 3-year exercise regimen compared with 73.9% among patients who received health education materials alone (HR 0.72, 95% CI 0.55-0.94, P=0.02), translating into a 28% reduced risk of disease recurrence or death, reported Christopher M. Booth, MD, of Queen’s University in Kingston, Ontario, Canada.

In addition, the study’s results suggested a substantial overall survival (OS) benefit with the exercise regimen as well, with 8-year OS of 90.3% in the exercise group and 83.2% in the health-education group (HR 0.63, 05% CI 0.43-0.94).

Booth also reported that the survival benefits associated with the exercise regimen came with just a “modest” increase in musculoskeletal adverse events (AEs).

“The CHALLENGE trial sets a new standard of care for colon cancer,” said Booth during a press briefing at the American Society of Clinical Oncology (ASCO) annual meeting. “A program of structured exercise after surgery and adjuvant chemotherapy meaningfully improves fitness, disease-free survival, and overall survival. These results represent a novel, first-in-class, anticancer effect, for a new form of cancer therapy.” The findings were published simultaneously in the New England Journal of Medicine.

“Moreover, the magnitude of benefit is substantial,” he said. “In fact it is comparable, and in some cases exceeds, the magnitude of benefit of many of our very good standard medical therapies in oncology.”

ASCO discussant Pamela Kunz, MD, of the Yale School of Medicine in New Haven, Connecticut, pointed out that “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 disease-free survival.”

“Exercise as an intervention is a no brainer and should be implemented broadly,” Kunz said.

Booth and colleagues noted that while preclinical and observational studies demonstrated that physical activity after treatment can lower the risk of cancer recurrence and death in patients with colorectal cancer, the results have been “inconclusive, given the methodologic limitations of observational designs.”

CHALLENGE was conducted at 55 sites (predominantly in Canada and Australia) and included 889 patients who had undergone resection of stage III or high-risk stage II adenoma of the colon. All of these patients had completed adjuvant chemotherapy within the past 2-6 months; had an ECOG performance-status score of 0 or 1; reported that they were currently exercising less than the equivalent of 150 minutes per week of moderate-to-vigorous intensity; and could complete at least two stages of a submaximal treadmill test or the 6-minute walk test.

Patients in the health-education group received general health-education materials promoting physical activity and healthy nutrition in addition to standard surveillance. Those in the exercise group received the health-education materials and attended mandatory behavioral support and supervised exercise sessions over the course of 3 years, with exercise tailored to each individual and varying from a brisk walk to circuit-training classes.

The median age of the patients in the study was 81, 51% were women, 90% had stage III disease, and 61% had received FOLFOX chemotherapy.

At baseline, median physical-function score on the 100-point 36-Item Short Form Survey (SF-36) — with a higher score indicating more favorable health — was 80.0 for the exercise group and 85.0 for the health-education group. Patients in the exercise group reported having greater improvement in physical function from baseline versus those in the health-education group at:

• 6 months: 7.1 vs 1.3 points, respectively
• 1 year: 6.8 vs 3.3
• 18 months: 7.2 vs 2.4
• 2 years: 6.1 vs 2.6
• 3 years: 6.1 vs 3.0

The exercise intervention met its goal of increasing moderate-to-vigorous physical activity from baseline by about 10 metabolic equivalent task-hours per week throughout the entire 3-year intervention. This increase is the equivalent of adding about 45-60 minutes of brisk walking three or four times per week or 25-30 minutes of jogging three or four times per week, said Booth and colleagues.

As for safety, musculoskeletal AEs occurred in 79 patients (18.5%) in the exercise group — eight of which were considered to be related to the exercise intervention — and in 53 patients (11.5%) in the health-education group.

Patient adherence to the exercise program shifted over the full trial. For instance, in the first 6 months, 83% were adherent to 12 mandatory behavioral-support sessions, while 79% stayed with 12 mandatory supervised exercise sessions, and 20% did the 12 recommended supervised exercise. During the last 2 years, adherence came in at 63% for the 24 mandatory behavioral-support sessions and 44% for the 24 recommended supervised exercise sessions.

Despite the study’s positive results, Booth warned that patients won’t be able to realize the benefits of a structured exercise regimen unless health systems, hospitals, and payers invest in these patient support programs.

“This intervention is empowering and achievable for patients, and with much, much lower costs than many of our therapies, and is also sustainable for health systems,” he added.