A structured exercise program after adjuvant chemotherapy for colon cancer improved survival and saved money.

In a preplanned cost-utility analysis of the phase III CHALLENGE trial, presented at the 2026 ASCO Annual Meeting¹ and published simultaneously in the Journal of Clinical Oncology,² the program was less costly and more effective than health education materials alone. The analysis showed gains in life-years and quality-adjusted life-years and lower total costs in the base-case analysis. The findings remained generally consistent when investigators tested different assumptions and scenarios.

Kelvin K. Chan, MD, PhD, FRCPC

“Following adjuvant chemotherapy for colon cancer, a structured exercise program improves disease-free survival and overall survival,” said Kelvin K. Chan, MD, PhD, FRCPC, of Sunnybrook Health Sciences Centre and the University of Toronto. “Despite its upfront cost, the structured exercise program improves quality-adjusted life-years, is cost-saving, and cost-effective.”

“The structured exercise program represents a win-win strategy for both costs and clinical benefits,” Dr. Chan said. “Our findings provide economic evidence to support its integration into routine clinical care.”

CHALLENGE Trial

The CHALLENGE trial enrolled patients with stage III or high-risk stage II colon cancer who had undergone curative-intent surgery and completed adjuvant chemotherapy. Participants were randomly assigned to a structured exercise program plus health education materials or to health education materials alone.

The structured exercise program was a 3-year intervention delivered by qualified personal trainers. Each session included behavioral coaching or supervised exercise. In the first year, mandatory sessions took place every 2 weeks; in years 2 and 3, they took place monthly.

Disease-free survival was the primary endpoint. At 5 years, the structured exercise program improved disease-free survival by 6.4% compared with health education materials alone (HR = 0.72; P = .017). According to Dr. Chan, this meant that for every 16 participants assigned to structured exercise, one recurrence or new cancer was prevented.

Overall survival was a key secondary endpoint. At 8 years, the structured exercise program improved overall survival by 7.1% compared with health education materials alone (HR = 0.63; P = .022). This meant that for every 14 participants assigned to structured exercise, one death was prevented, he reported.

Since publication of the primary CHALLENGE results, the structured exercise program has been incorporated into major clinical practice guidelines, including ASCO and NCCN guidelines, according to Dr. Chan.

Cost-Utility Analysis

The current analysis was a preplanned economic evaluation of the CHALLENGE trial. Investigators used prospectively collected data from trial participants and adopted the perspective of the Canadian public health-care payer.

The base case used direct medical costs in 2024 Canadian dollars, a 5-year time horizon, and a 1.5% discount rate. Cost categories included the exercise program, recurrence or new primary cancer, anticancer therapies, and hospitalizations. Outcomes were measured in life-years and quality-adjusted life-years.

The structured exercise program cost $2,917 per patient. But that upfront cost was offset by lower costs for cancer recurrence and anticancer therapy. Overall, the program was associated with total cost savings of $1,589 per patient compared with health education materials alone. It also produced gains of 0.05 life-years and 0.10 quality-adjusted life-years.

Cost-Effectiveness Findings

In analyses testing uncertainty around the results, the structured exercise program was cost-saving and more effective in 53% of simulations and had an 80% probability of being cost-effective at a willingness-to-pay threshold of $50,000 per quality-adjusted life-year.

The findings held up in most additional analyses. When overhead costs were included, the program was no longer cost-saving but remained cost-effective, with an incremental cost-utility ratio of $4,405 per quality-adjusted life-year.

To put the findings in context, Dr. Chan said the investigators reviewed the cost-effectiveness of cancer drugs recommended for public reimbursement in Canada in 2025. The mean incremental cost-effectiveness ratio for those drugs was approximately $435,000 per quality-adjusted life-year.

Implementation Questions Remain

He noted several limitations, including the potential for salaried staff to generate higher costs than hourly staff if there is substantial downtime between patients, making efficient implementation important. The analysis also did not include all indirect costs, such as lost leisure time, informal caregiving costs, or costs incurred by employers replacing absent employees.

Quality-of-life data were collected during the first 5 years only. The analysis used the Canadian payer perspective, although Dr. Chan said the results are likely generalizable to other jurisdictions. In health systems where cancer treatment costs are higher than in Canada, he noted, cost savings may be even greater.

Expert Perspective

Discussing the study, Alan P. Venook, MD, FASCO, of the University of California, San Francisco, called the Canadian Cancer Trials Group’s work “the most remarkable clinical research effort I’ve seen in my career as a medical oncologist and clinical trialist,” and said the survival impact of structured exercise was difficult to ignore. He noted that the trial took 15 years and continued through the COVID-19 pandemic.

Alan P. Venook, MD, FASCO

“What’s even more remarkable is that it worked,” Dr. Venook emphasized.

The key message from CHALLENGE, he said, is that “for every 14 patients who have structured exercise, one life is saved.”

He called it a “stunning result,” adding that the effect of the intervention is something “some people are still finding hard to believe.”

He also highlighted the economic findings.

“We saw it didn’t cost [money], it saved money,” he said, referring to the $1,589 per-patient savings. “Not many things we do save money in our patients.”

Although the findings are compelling, Dr. Venook said implementation will be a challenge. Delivering structured exercise is not simple, and health systems will need to determine how best to support it.

“Implementation and delivery of structured exercise is not easy,” he said, noting that payer support will be important.

Dr. Venook also compared the survival impact of structured exercise with the improvement seen with FOLFOX in the MOSAIC trial,³ while acknowledging that the trials were not directly comparable because CHALLENGE enrolled patients who had already completed adjuvant therapy and had no evidence of recurrence.

Even with that caveat, he said, “the incremental improvement on top of FOLFOX is stunning, and we can’t ignore that.”

For clinicians, Dr. Venook suggested the findings should change how they talk with patients after adjuvant therapy.

When discussing chemotherapy, he said, oncologists do not merely “discuss and facilitate.” They recommend treatment and help arrange it. Structured exercise, he argued, should be approached more seriously than a casual lifestyle recommendation.

“This is not really an option,” Dr. Venook said. “This is really something that appears to make a big difference.” 

DISCLOSURE: Dr. Chan reported no relevant conflicts of interest. Dr. Venook reported consulting or advisory roles with AbbVie, Amgen, Eisai, Exact Sciences, Exelixis, INTERA, and Pfizer, as well as royalties from UpToDate for authoring and maintaining two chapters.

REFERENCES

1. Chan KK, Chu RW, Cheung MC, et al: Structured exercise program following adjuvant chemotherapy for colon cancer: A cost-utility analysis of the CHALLENGE trial. 2026 ASCO Annual Meeting. Abstract 3507. Presented May 31, 2026.

2. Chan KK, Chu RW, Cheung MC, et al: Structured exercise program following adjuvant chemotherapy for colon cancer: A cost-utility analysis of the CHALLENGE trial. J Clin Oncol Published online May 31, 2026.

3. André T, de Gramont A, Vernerey D, et al: Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: Updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol. 33:4176-4187, 2015.