Neoadjuvant Exercise Therapy in Prostate Cancer: A Phase 1, Decentralized Nonrandomized ControlledTrial
Mené sur 53 patients atteints d'un cancer de la prostate (âge médian : 61 ans), cet essai de phase I détermine la faisabilité et l'effet, sur la prolifération des cellules cancéreuses, de différentes intensités d'exercices physiques avant un traitement chirurgical
Importance : Observational data have shown that postdiagnosis exercise is associated with reduced risk of prostate cancer death. The feasibility and tumor biological activity of exercise therapy is not known. Objective : To identify recommended phase 2 dose of exercise therapy for patients with prostate cancer. Design, Setting, and Participants : This single-center, phase 1a dose-finding trial was conducted at a tertiary cancer center using a patientcentric, decentralized platform and included 53 inactive men with treatment-naive localized prostate cancer scheduled to undergo surgical resection between June 2019 and January 2023. Data were analyzed in June 2024. Intervention : Six escalated exercise therapy dose levels ranging from 90 to 450 minutes per week of individualized, moderate-intensity treadmill walking, allocated using adaptive continual reassessment. All exercise therapy sessions were conducted remotely with real-time monitoring. Main Outcomes and Measures : Feasibility was evaluated by relative exercise dose intensity (REDI). A dose level was considered feasible if 70% or more of patients achieved an REDI of 75% or greater. Activity end points were changes in tumor cell proliferation (Ki67) and plasma prostate-specific antigen levels between pretreatment and postintervention. Safety and changes in patient physiology were also assessed. Results : A total of 53 men were enrolled (median [IQR] age, 61 [56-66] years). All dose levels were feasible (≥75% REDI). The mean (95% CI) changes in Ki67 were 5.0% (–4.3% to 14.0%) for 90 minutes per week, 2.4% (–1.3% to 6.2%) for 150 minutes per week, –1.3% (–5.8% to 3.3%) for 225 minutes per week, –0.2% (–4.0% to 3.7%) for 300 minutes per week, –2.6% (–9.2% to 4.1%) for 375 minutes per week, and 2.2% (−0.8% to 5.1%) for 450 minutes per week. Changes in prostate-specific antigen levels were 1.0 ng/mL (–1.8 to 3.8) for 90 minutes per week, 0.2 ng/mL (–1.1 to 1.5) for 150 minutes per week, –0.5 ng/mL (–1.2 to 0.3) for 225 minutes per week, –0.2 (–1.7 to 1.3) for 300 minutes per week, –0.7 ng/mL (–1.7 to 0.4) for 375 minutes per week, and –0.9 ng/mL (–2.4 to 0.7) for 450 minutes per week. No serious adverse events were observed. Overall, 225 minutes per week (approximately 5 minutes per treatment at 5 times weekly) was selected as the recommended phase 2 dose. Conclusions and Relevance : The results of this nonrandomized clinical trial suggest that neoadjuvant exercise therapy is feasible and safe with promising activity in localized prostate cancer.