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Effects of Exercise on Cardiorespiratory Fitness and Biochemical Progression in Men With Localized Prostate Cancer Under Active SurveillanceThe ERASE Randomized Clinical Trial

Educational Objective
To learn the effects of exercise on biochemical progression in men with localized prostate cancer under active surveillance.

1 Credit CME

JAMA Oncology

Published Online: August 19, 2021

Original Investigation

Article Information and Disclosures

Dong-Woo Kang, PhD^1,2;

Adrian S. Fairey, MD³;

Normand G. Boulé, PhD¹;

Catherine J. Field, PhD⁴;

Stephanie A. Wharton, BSc¹;

Kerry S. Courneya, PhD¹

Author Affiliations

¹Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, Alberta, Canada
²Now with Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts
³Division of Urology, Department of Surgery, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada
⁴Department of Agricultural, Food and Nutritional Science, Faculty of Agricultural, Life and Environmental Sciences, University of Alberta, Edmonton, Alberta, Canada

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Key Points

Question Does a high-intensity interval training program improve cardiorespiratory fitness and delay the biochemical progression of prostate cancer in patients who are undergoing active surveillance?

Findings In this randomized clinical trial of 52 male participants with prostate cancer under active surveillance, 12 weeks of high-intensity interval training significantly improved peak oxygen consumption, decreased prostate-specific antigen levels, and decreased prostate-specific antigen velocity compared with usual care. It also inhibited the growth of prostate cancer cell line LNCaP in this patient population.

Meaning The findings of this study indicate that exercise may be an effective intervention for improving cardiorespiratory fitness and suppressing the progression of prostate cancer for patients undergoing active surveillance.

Abstract

Importance Men with prostate cancer who are undergoing active surveillance are at an increased risk of cardiovascular death and disease progression. Exercise has been shown to improve cardiorespiratory fitness, physical functioning, body composition, fatigue, and quality of life during and after treatment; however, to date only 1 exercise study has been conducted in this clinical setting.

Objective To examine the effects of exercise on cardiorespiratory fitness and biochemical progression in men with prostate cancer who were undergoing active surveillance.

Design, Setting, and Participants The Exercise During Active Surveillance for Prostate Cancer (ERASE) trial was a single-center, 2-group, phase 2 randomized clinical trial conducted at the University of Alberta, Edmonton, Canada. Eligible patients were recruited from July 24, 2018, to February 5, 2020. Participants were adult men who were diagnosed with localized very low risk to favorable intermediate risk prostate cancer and undergoing active surveillance. They were randomized to either the high-intensity interval training (HIIT) group or usual care group. All statistical analyses were based on the intention-to-treat principle.

Interventions The HIIT group was asked to complete 12 weeks of thrice-weekly, supervised aerobic sessions on a treadmill at 85% to 95% of peak oxygen consumption (V̇o₂). The usual care group maintained their normal exercise levels.

Main Outcomes and Measures The primary outcome was peak V̇o₂, which was assessed as the highest value of oxygen uptake during a graded exercise test using a modified Bruce protocol. Secondary and exploratory outcomes were indicators of biochemical progression of prostate cancer, including prostate-specific antigen (PSA) level and PSA kinetics, and growth of prostate cancer cell line LNCaP.

Results A total of 52 male patients, with a mean (SD) age of 63.4 (7.1) years, were randomized to either the HIIT (n = 26) or usual care (n = 26) groups. Overall, 46 of 52 participants (88%) completed the postintervention peak V̇o₂ assessment, and 49 of 52 participants (94%) provided blood samples. Adherence to HIIT was 96%. The primary outcome of peak V̇o₂ increased by 0.9 mL/kg/min in the HIIT group and decreased by 0.5 mL/kg/min in the usual care group (adjusted between-group mean difference (1.6 mL/kg/min; 95% CI, 0.3-2.9; P = .01). Compared with the usual care group, the HIIT group experienced decreased PSA level (−1.1 μg/L; 95% CI, −2.1 to 0.0; P = .04), PSA velocity (−1.3 μg /L/y; 95% CI, −2.5 to −0.1; P = .04), and LNCaP cell growth (−0.13 optical density unit; 95% CI, −0.25 to −0.02; P = .02). No statistically significant differences were found in PSA doubling time or testosterone.

Conclusions and Relevance The ERASE trial demonstrated that HIIT increased cardiorespiratory fitness levels and decreased PSA levels, PSA velocity, and prostate cancer cell growth in men with localized prostate cancer who were under active surveillance. Larger trials are warranted to determine whether such improvement translates to better longer-term clinical outcomes in this setting.

Trial Registration ClinicalTrials.gov Identifier: NCT03203460

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Article Information

Accepted for Publication: May 20, 2021.

Published Online: August 19, 2021. doi:10.1001/jamaoncol.2021.3067

Corresponding Author: Kerry S. Courneya, PhD, Faculty of Kinesiology, Sport, and Recreation, University of Alberta, 1-113 University Hall, Edmonton, Alberta T6G 2H9, Canada (kerry.courneya@ualberta.ca).

Author Contributions: Dr Kang and Prof Courneya had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Kang, Fairey, Boulé, Courneya.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Kang.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Kang, Fairey, Boulé, Courneya.

Obtained funding: Kang, Courneya.

Administrative, technical, or material support: Kang, Fairey, Wharton, Courneya.

Supervision: Kang, Fairey, Boulé, Field, Courneya.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was supported by grant 389507 from the Canadian Institutes of Health Research and grant D2017-1820 from Prostate Cancer Canada. Prof Courneya was supported by the Canada Research Chairs Program. Dr Kang was supported by the Alberta Innovates Graduate Studentship. Exercise equipment was donated by Apple Fitness, Edmonton, Alberta, Canada.

Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We acknowledge the support of the following individuals: Niels-Erik Jacobsen, MD, Michael Chetner, MD, Sarah Rayner, RN, and Nupur Agarwal, CCPA, Northern Alberta Urology Center, assisted with patient recruitment; Sue Goruk, PhD, and Dhruvesh Patel, BSc, University of Alberta, assisted with blood assays; and Andria Morielli, PhD, Terri Wood, BSc, Ki-Yong An, PhD, Fernanda Arthuso, MSc, Stephanie Ntoukas, BSc, Spencer Allen, BSc, and Morgan Corbett, BSc, University of Alberta, assisted with exercise testing and intervention. These individuals received no additional compensation, outside of their usual salary, for their contributions. We also thank the study participants for their time and commitment.

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 credit toward the CME of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.