Rigorous exercise not only boosted cardiorespiratory fitness, but also improved indicators of prostate cancer biochemical progression in patients undergoing active surveillance, according to results of a randomised trial.
Patients participating in a 12-week high-intensity interval training (HIIT) regimen saw an increase in peak oxygen consumption (VO2) – the study's primary outcome – of 0.9 mL/kg/min, while a usual-care group saw a decrease of 0.5 mL/kg/min, for an adjusted between-group mean difference of 1.6 mL/kg/min , reported Kerry Courneya, of the University of Alberta in Canada, and colleagues.
Additionally, the patients in the HIIT programme experienced decreased prostate-specific antigen (PSA) levels, PSA velocity, and lymph node carcinoma of the prostate cell growth, “suggesting that HIIT may have played an inhibitory role in prostate cancer cell growth in this setting”, they wrote in JAMA Oncology.
Patients on active surveillance for prostate cancer have a three times higher risk of cardiovascular disease-specific death than prostate cancer-specific death, and more than half will experience disease progression and require radical treatment within 10 years, the authors noted.
“Interventions during active surveillance to boost cardiovascular health, delay disease progression, and precondition these men for possible radical treatments would be desirable," they wrote.
The single-centre, phase II Exercise During Active Surveillance for Prostate Cancer (ERASE) trial included 52 patients (mean age 63, 89% white) who were randomised 1_1 to either the HIIT regimen or usual care. Patients randomised to HIIT participated in a supervised exercise programme three times a week over a 12-week period that involved treadmill work at 85% to 95% of peak VO2. Usual care patients maintained their usual exercise levels.
Of the 52 patients in the trial, 88% completed the post-intervention peak VO2 assessment, while 94% provided blood samples.
Patients in the HIIT programme also had improved increased peak VO2 in liter per minute, upper body strength, and lower body flexibility compared with the usual care group.
In addition, Courneya and colleagues noted that patients in the HIIT group experienced improved PSA doubling time, but the difference between groups was not statistically significant. There was also no significant difference in testosterone levels.
“It is worth noting that the usual care group did in fact experience a diminution in VO2 peak,” wrote Dr Neha Vapiwala of Perelman School of Medicine at the University of Pennsylvania in Philadelphia, in an accompanying commentary. “This suggests cardiovascular deconditioning over a 12-week period relative to baseline when following the usual care protocol, which raises the possibility that participation in the control group of this study may have promoted a more sedentary lifestyle than typical for some patients, in turn contributing to the dramatic and statistically significant difference seen.”
Courneya and colleagues acknowledged several study limitations, such as the fact that they needed to shorten the intervention period for several participants because of the onset of the COVID-19 pandemic, as well as potential recruitment bias (i.e., more fit and active men) and a lack of long-term follow-up for clinical outcomes.
“Larger randomised clinical trials are warranted to determine whether improvements in cardiorespiratory fitness and prostate cancer-related markers translate into better long-term clinical outcomes in men with prostate cancer on active surveillance,” they concluded.
Vapiwala said that the results with HIIT alone, without dietary changes, in men on active surveillance are "novel and noteworthy”. The ERASE trial could empower prostate cancer patients "to be in better physical, functional, and psychological shape for any future medical interventions they may need”, she wrote.
Study details
Effects of Exercise on Cardiorespiratory Fitness and Biochemical Progression in Men With Localized Prostate Cancer Under Active Surveillance – The ERASE Randomized Clinical Trial
Dong-Woo Kang, Adrian S. Fairey, Normand G. Boulé, Catherine J. Field, Stephanie A. Wharton, Kerry S. Courneya
Published in JAMA Oncology 19 August 2021
Key Points
Question
Does a high-intensity interval training programme improve cardiorespiratory fitness and delay the biochemical progression of prostate cancer in patients who are undergoing active surveillance?
Findings
In this randomised 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 one 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-centre, two-group, phase 2 randomised clinical trial conducted at the University of Alberta, Canada. Eligible patients were recruited from 24 July 2018, to 5 February 2020. Participants were adult men diagnosed with localised very low risk to favourable intermediate risk prostate cancer and undergoing active surveillance. They were randomised 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 localised 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.
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