ImportanceObservational 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.ObjectiveTo identify recommended phase 2 dose of exercise therapy for patients with prostate cancer.Design, Setting, and ParticipantsThis 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.InterventionSix 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 MeasuresFeasibility 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.ResultsA 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 RelevanceThe results of this nonrandomized clinical trial suggest that neoadjuvant exercise therapy is feasible and safe with promising activity in localized prostate cancer.Trial RegistrationClinicalTrials.gov Identifier: NCT03813615

中文翻译：

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前列腺癌的新辅助运动疗法


重要性观察数据表明，诊断后运动与降低前列腺癌死亡风险有关。运动疗法的可行性和肿瘤生物活性尚不清楚。目的确定前列腺癌患者推荐的 2 期运动疗法剂量。设计、设置和参与者这项单中心、1a 期剂量探索试验在三级癌症中心使用以患者为中心的分散平台进行，包括 53 名计划在 2019 年 6 月至 2023 年 1 月期间接受手术切除的初治局限性前列腺癌不活跃男性。干预 6 个递增的运动疗法剂量水平，从每周 90 到 450 分钟不等，进行个体化、中等强度的跑步机步行，使用适应性持续重新评估进行分配。所有运动疗法均在实时监测下远程进行。主要结局和措施通过相对运动剂量强度 （REDI） 评估可行性。如果 70% 或更多的患者达到 75% 或更高的 REDI，则认为剂量水平是可行的。活动终点是治疗前和干预后之间肿瘤细胞增殖 （Ki67） 和血浆前列腺特异性抗原水平的变化。还评估了安全性和患者生理学的变化。结果共纳入 53 例男性 （中位 [IQR] 年龄，61 [56-66] 岁）。所有剂量水平都是可行的 （≥75% REDI）。Ki67 的平均 （95% CI） 变化为每周 90 分钟为 5.0%（-4.3% 至 14.0%），每周 150 分钟为 2.4%（-1.3% 至 6.2%），每周 225 分钟为 -1.3%（-5.8% 至 3.3%），每周 300 分钟为 -0.2%（-4.0% 至 3.7%），每周 375 分钟为 -2.6%（-9.2% 至 4.1%），每周 450 分钟为 2.2%（-0.8% 至 5.1%）。 前列腺特异性抗原水平的变化为：每周 90 分钟 1.0 ng/mL（-1.8 至 3.8），每周 150 分钟 0.2 ng/mL（-1.1 至 1.5），每周 225 分钟，-0.2 ng/mL（-1.2 至 0.3），每周 300 分钟-0.2（-1.7 至 1.3），每周 375 分钟-0.7 ng/mL（-1.7 至 0.4），每周 375 分钟， 以及 -0.9 ng/mL（-2.4 至 0.7），每周 450 分钟。未观察到严重不良事件。总体而言，每周 225 分钟（每次治疗约 5 分钟，每周 5 次）被选为推荐的 2 期剂量。结论和相关性这项非随机临床试验的结果表明，新辅助运动疗法是可行且安全的，在局限性前列腺癌中具有很好的活性。试验注册临床试验。gov 标识符： NCT03813615