What the Oncology Field Can Learn From the CHALLENGE Trial

As the oncology community continues to seek innovative ways to improve patient outcomes, the recent publication of the phase 3 CHALLENGE trial marks a pivotal moment in our understanding of the role of exercise in cancer care. In this Letter From the Editor, Dr. Rahul Banerjee, OncData Editor in Chief, reflects on the trial’s groundbreaking findings, which demonstrate that structured exercise interventions can yield survival benefits rivaling those of established cancer therapies.

View a video perspective on the CHALLENGE trial here!

What Is the CHALLENGE Trial?

The phase 3 CHALLENGE trial, published last month in the New England Journal of Medicine simultaneously with an oral presentation at the 2025 American Society of Clinical Oncology (ASCO) meeting, will be the subject of many journal clubs for years to come—and for good reason. In this large study of almost 900 patients with colon cancer, patients were randomized to either structured exercise (with supervised support for physical activity over a 3-year period) or exercise handouts alone. The results were truly remarkable: better patient-reported physical functioning, longer disease-free survival, and longer overall survival. In particular, eight-year overall survival was 90% in the exercise group versus 83% in the handouts alone—a statistically significant, clinically meaningful, and honestly shocking result.

Understanding the Mechanisms

Many in the field have wondered how a non-pharmacological intervention could work so well, with a hazard ratio for death (0.63, with a 95% confidence interval of 0.43-0.94) rivaling that of our best cancer drugs. Other physicians have cast doubt on the magnitude of benefit of the findings, reasoning that a difference in exercise could not explain an improvement in survival unless patients lost weight or improved waist circumference significantly. To be clear, six-minute-walk test distances did improve slightly in the exercise group, approximately 13-30 meters. This raises two questions: how can exercise make such an impactful difference in overall survival? And how do we replicate this successful formula?

The answer to the first question is more straightforward: for patients living with cancer—particularly in CHALLENGE, where over a third of patients were aged 65 or older—even small improvements in physical activity can add up substantially over time. Being able to walk 10-20 additional feet per minute may not seem like much, but it can mean a huge amount in terms of patient independence and ability to maintain instrumental activities of daily living. These may in turn allow patients to maintain healthier behaviors and be at lower risk of dying, whether from cancer or from something else. Similar associations have been seen for other solid tumors as well. Whether the biology of disease recurrence is modified by exercise, perhaps through better immune surveillance, is quite plausible based on an increasing amount of correlative data.

Implementing Exercise Into Practice

The answer to the second question is trickier: can we set up a CHALLENGE-style program for our patients in clinic tomorrow, and can they ideally be reimbursed for it? Such a structured exercise program cannot be created overnight, but the trial’s incredible results suggest that such efforts should be promoted and reimbursed. Unfortunately, just providing cancer survivors with a wearable activity-monitoring device has not proven to be helpful in several randomized trials (examples one, two, and three). Such efforts almost certainly have to be integrated into a comprehensive program with longitudinal support. Evidently, even if patients do not lose weight or double their gait speeds, the results speak for themselves—when patient-reported fitness improves, improvements in overall survival may well follow!

About Dr. Banerjee

Rahul Banerjee, MD, FACP, is an Assistant Professor in the Division of Medical Oncology at the University of Washington. He also holds a faculty appointment at the Fred Hutchinson Cancer Center in Seattle, Washington. Dr. Banerjee previously completed his Hematology/Oncology Fellowship and Advanced BMT/CAR-T Fellowship at the University of California, San Francisco. His clinical interests are in multiple myeloma, AL amyloidosis, and CAR-T therapy. His research interests are in toxicity management, digital health, and the patient experience.