Authors:
Stacey A Kenfield, Nicolas H Hart, Kerry S Courneya, Rosemary Greenwood , June M Chan, Jennette Sison, Li Zhang, Sarah RudmaN, Leah Ung, Moritz Schumann, Erin L Van Blarigan, Sam McKeown, Charles J Ryan, James Catto, Daniel A Galvão, Robert U Newton, Fred Saad; INTERVAL-GAP4 Site Investigators and INTERVAL-GAP4 Steering and Management Committees (Stephen R. Plymate, Committee Member
University of Washington affiliated authors are displayed in bold.
✪ Open Access
Published: December 2025
Read the full text in the open access journal European Urology Open Science
Abstract:
Background and objective
Physical activity is associated with a lower risk of mortality in men with prostate cancer (PC); yet, randomised controlled trials with survival endpoints are nonexistent. INTense ExeRcise for surviVAL-Global Action Plan 4 (INTERVAL-GAP4) was a global phase 3 trial designed to test whether structured, hybrid-supervised/self-managed exercise improves survival in men with metastatic PC. The trial was stopped early due to poor accrual. This paper reports feasibility and implementation outcomes.
Methods
Men with metastatic PC were randomised (1:1) to a supervised/self-managed moderate- to high-intensity resistance and aerobic programme (three sessions per week for 2 yr) or to self-directed exercise. We evaluated site activation, recruitment, year 1 adherence, adverse events, and barriers to global trial feasibility. Efficacy outcomes—including survival, physical fitness, and biomarker results—will be reported separately.
Key findings and limitations
Of 21 activated sites across seven countries, 13 (62%) randomised patients. Of 938 patients approached, 232 (25%) consented and 145 (15%) were randomised (75 in the intervention and 70 in the control group) between April 2016 and February 2023. The median age was 70 yr (range: 44–89 yr). The study closed early after reaching 17% of the intended target. The median adherence in the intervention arm was 84% (interquartile range: 61–95%), with no difference between metastatic castrate-resistant and hormone-sensitive PC. At 12 mo, 58% of intervention participants met exercise guidelines versus 24% of controls. In year 1, 162 adverse events occurred in the intervention group and 109 in the control group; 19 adverse events were study related, all in the intervention arm. The major feasibility challenges included administrative burden, infrastructure limitations, logistics of supervised exercise delivery, and coronavirus disease 2019 disruptions.
Conclusions and clinical implications
While high adherence to a demanding exercise programme was achieved in selected metastatic PC patients, global recruitment proved difficult. Future large-scale exercise-oncology trials require streamlined protocols, realistic timelines, and greater alignment with site resources. Implementation science research is needed to support integration of exercise into routine advanced cancer care. A forthcoming paper will present the trial’s survival and physical fitness efficacy outcomes.
**This abstract is posted with permission under the Creative Commons Attribution 4.0 International License**