Can Exercise Be Used as Medicine in Colon Cancer?

The CHALLENGE Trial

“The CHALLENGE trial was, for those of us who were at ASCO 2025, the talk of the meeting,” noted Dr. Freedland. Dr. Gong added, “It was very attractive and gained a lot of buzz at ASCO, especially since the New England Journal paper came out. I think it has a lot of potential broad applicability to not just colon cancer patients, but patients across other cancer types and disease types.”

The trial was a multicenter, phase 3 study enrolling 889 patients who had completed curative surgery and adjuvant chemotherapy for stage III (and some high-risk stage II) colon cancer. Patients were randomized to two groups: a control group that received health education materials alone, and an experimental group consisting of a three-year structured exercise program. The program included supervised exercise sessions and support from physical activity specialists over three years. The primary end point was disease-free survival (DFS), which was a composite end point of either death or recurrence of cancer.

The results were striking. The three-year structured program had a superior DFS benefit compared to the control arm: an absolute DFS benefit of 6% at 5 years, with a hazard ratio of 0.72. Additionally, there was a 7% improvement in overall survival at 8 years, and the rate of new primary cancers was significantly reduced.

“This was a positive study,” emphasized Dr. Gong. “Its significance is that it becomes one of the first phase 3 trials out there to support the concept of exercise as a way to improve survival for colon cancer survivors, whereas it was largely observational data before this. We now have level 1 data for the first time.”

Implementation Challenges in Clinical Practice

While the results are striking, both clinicians acknowledged the challenges of implementing such a program in routine practice. Dr. Gong noted, “I think the feasibility will one of the biggest concerns—having the resources to do a three-year structured program. I don’t think many clinics have the personnel and the support to do this.” However, both agreed on the value of having a target, such as an aerobic exercise goal of 150 minutes a week of brisk walking (3 to 4 miles per hour), to counsel patients about. “People like having a number and want to achieve that number, so we can give them a target for structured exercise,” Dr. Freedland added.

Addressing Equity and Adherence

Equity and adherence are also key factors. Dr. Freedland raised concerns about disparities: “Not everyone has access to a gym, and not everyone lives in a neighborhood where it’s safe to go walking around. How do we implement this equitably for all?” They note that in the study, adherence in the first year was above 80%, and by the third year, it dropped to nearly 60%, which poses a challenge in the real-world setting. Yet, Dr. Freedland found optimism in the data: “Even with suboptimal adherence, we still saw impressive results, so it doesn’t necessarily require 100% percent adherence. The message is to not give up.”

Patient Counseling and Clinical Application

When asked how he is translating these findings into patient care, Dr. Gong described a dual approach: “I think there are two hats to this. With my patient-to-provider interaction hat, I’m telling patients that we have always suspected these conclusions, but now we have phase 3 data and level 1 evidence. We can give them the target that the study was envisioning—say, walking approximately 150 minutes at 3 to 4 miles per hour each week. That should be a goal.”

Regarding the clinical side, he explained: “On the other side is the programmatic clinician hat. How do we systematically apply this to all the patients?” He is currently talking with supportive care and physical medicine rehabilitation groups at Cedars-Sinai about internal referrals or third-party vendors that can provide structured programs such as the one outlined in the trial. Regardless of method of implementation, Dr. Gong concluded, “I do believe that the exercise concept is crucial, and it’s potentially applicable across a whole spectrum of cancer types.”

Key Takeaways

• The CHALLENGE trial provides level 1 evidence that structured exercise improves disease-free and overall survival in colon cancer survivors.
• Implementing a 3-year supervised exercise program in real-world settings will require creative solutions in resource and equity challenges.
• Even partial adherence to exercise regimens can yield meaningful benefits.
• The principles of exercise as medicine may apply broadly across cancer types and stages.

About the Speakers

Stephen Freedland, MD, is Director of the Center for Integrated Research in Cancer and Lifestyle and Associate Director for Education and Training at the Cedars-Sinai Samuel Oschin Comprehensive Cancer Institute in Los Angeles. He is also the Warschaw Robertson Law Families Chair in Prostate Cancer and a Professor in the Department of Urology at Cedars-Sinai. He also holds a Staff Physician appointment at the Durham VA Medical Center in Durham, North Carolina. Dr. Freedland has published over 700 articles and served on numerous AUA and ASCO guideline panels for prostate cancer. His research interests include the role of diet, lifestyle, and obesity in cancer, cancer health disparities, and cancer risk stratification.

Jun Gong, MD, is an Associate Professor of Medicine and Medical Director of Colorectal Cancer at Cedars-Sinai Medical Center, where he is part of the Gastrointestinal Disease Research Group, the Pancreatic Cancer Research Group, and the Urologic Oncology Program. His primary interests are in translational and clinical research through early therapeutic trials and biomarker development to improve patient outcomes in gastrointestinal and genitourinary cancers.