Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2024 Sep 1;10(9):1187-1194.
doi: 10.1001/jamaoncol.2024.2156.

Neoadjuvant Exercise Therapy in Prostate Cancer: A Phase 1, Decentralized Nonrandomized ControlledTrial

Lee W Jones  1   2 , Chaya S Moskowitz  1 , Catherine P Lee  1 , Gina A Fickera  1 , Su S Chun  1 , Meghan G Michalski  1 , Kurtis Stoeckel  1 , Whitney P Underwood  1 , Jessica A Lavery  1 , Umeshkumar Bhanot  1   2 , Irina Linkov  1 , Chau T Dang  1   2 , Behfar Ehdaie  1   2 , Vincent P Laudone  1   2 , James A Eastham  1   2 , Anne Collins  1 , Patricia T Sheerin  1 , Lydia Y Liu  3   4   5 , Stefan E Eng  3   4   5 , Paul C Boutros  3   4   5   6   7
Affiliations
Clinical Trial

Neoadjuvant Exercise Therapy in Prostate Cancer: A Phase 1, Decentralized Nonrandomized ControlledTrial

Lee W Jones et al. JAMA Oncol. .

Erratum in

  • Error in Abstract.
    [No authors listed] [No authors listed] JAMA Oncol. 2024 Sep 1;10(9):1294. doi: 10.1001/jamaoncol.2024.4464. JAMA Oncol. 2024. PMID: 39297925 Free PMC article. No abstract available.

Abstract

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 45 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.

Trial registration: ClinicalTrials.gov Identifier: NCT03813615.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Jones reported stock ownership in Pacylex and Illumisonics outside the submitted work. Dr Moskowitz reported grants from the National Institutes of Health (NIH) and National Cancer Institute during the conduct of the study. Dr Lavery reported grants from National Cancer Institute (P30 CA008748) during the conduct of the study and salary support paid to their institution from the American Association of Cancer Research Project Genomics Evidence Neoplasia Information Exchange Biopharma Collaborative. Dr Boutros reported grants from NIH during the conduct of the study and advisory board service for BioSymetrics Inc, Intersect Diagnostics Inc, and Sage Bionetworks outside the submitted work. Ms Lavery is supported by American Association for Cancer Research Project GENIE BPC. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Study Flowchart
PSA indicates prostate-specific antigen.
Figure 2.
Figure 2.. Exercise Therapy Treatment Summary
Total number of exercise sessions completed by each patient in each dose level.
Figure 3.
Figure 3.. Tumor Biological Activity
A, Absolute percentage delta changes in tumor cell proliferation (Ki-67) from pretreatment to postintervention per exercise therapy dose level. B, Absolute delta changes in prostate-specific antigen (PSA; ng/mL [to convert to μg/L, multiply by 1]) from pretreatment to postintervention per exercise therapy dose level.
See this image and copyright information in PMC

Comment on

References

    1. Iyengar NM, Jones LW. Development of exercise as interception therapy for cancer: a review. JAMA Oncol. 2019;5(11):1620-1627. doi: 10.1001/jamaoncol.2019.2585 - DOI - PMC - PubMed
    1. Friedenreich CM, Wang Q, Neilson HK, Kopciuk KA, McGregor SE, Courneya KS. Physical activity and survival after prostate cancer. Eur Urol. 2016;70(4):576-585. doi: 10.1016/j.eururo.2015.12.032 - DOI - PubMed
    1. Kenfield SA, Stampfer MJ, Giovannucci E, Chan JM. Physical activity and survival after prostate cancer diagnosis in the health professionals follow-up study. J Clin Oncol. 2011;29(6):726-732. doi: 10.1200/JCO.2010.31.5226 - DOI - PMC - PubMed
    1. Richman EL, Kenfield SA, Stampfer MJ, Paciorek A, Carroll PR, Chan JM. Physical activity after diagnosis and risk of prostate cancer progression: data from the cancer of the prostate strategic urologic research endeavor. Cancer Res. 2011;71(11):3889-3895. doi: 10.1158/0008-5472.CAN-10-3932 - DOI - PMC - PubMed
    1. Wang Y, Jacobs EJ, Gapstur SM, et al. Recreational physical activity in relation to prostate cancer–specific mortality among men with nonmetastatic prostate cancer. Eur Urol. 2017;72(6):931-939. doi: 10.1016/j.eururo.2017.06.037 - DOI - PubMed

Associated data