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Original Investigation
August 19, 2021

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

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
JAMA Oncol. Published online August 19, 2021. doi:10.1001/jamaoncol.2021.3067
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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