Hitting the Gym: High Intensity Interval Training May Be Associated with Reduced PSA Levels

High-intensity interval training (HIIT) was associated with suppressed prostate cancer progression, as well as improved cardiorespiratory fitness, in patients undergoing active surveillance.¹

In the randomized, single-center, 2-group, phase 2 ERASE trial (NCT03203460), a cohort of 52 male patients with prostate cancer under active surveillance and undergoing 12 weeks of HIIT experienced a significant decrease in prostate-specific antigen (PSA) levels (95% CI, −2.1 to 0.0; P = .04), and prostate-specific antigen velocity (PSAV; 95% CI, −2.5 to −0.1; P = .04). The HIIT group also displayed favorable PSA doubling time (PSADT), compared with the control group, although the findings were not statistically significant (17.9 months; 95% CI, −3.8 to 39.6; P = .10).

Additionally, peak oxygen consumption was significantly improved as a result of the exercise, and prostate cancer cell line (LNCaP) growth was inhibited (−0.13 optical density unit; 95% CI, −0.25 to −0.02; P = .02).

“To our knowledge, the ERASE trial was the first randomized clinical trial to examine the efficacy of HIIT in men with localized prostate cancer undergoing active surveillance,” wrote lead author, Dong-Woo Kang, PhD, University of Alberta, Edmonton, Alberta, Canada. “These improvements appear to be meaningful and may translate into better outcomes for patients with prostate cancer who are being managed by active surveillance.”

A total of 52 patients were randomized to 2 groups. Within both groups, the mean age was 63.4 years. Eighty-nine percent self-identified as White individuals. To be eligible to participate, the men needed to be 18 years or older, have a diagnosis of very low- to favorable intermediate-risk prostate cancer, to be under active surveillance and have no plans for immediate treatment, as well as be medically cleared for participate, and physically able to complete a baseline fitness test. Participants could not already be engaging in vigorous-intensity exercise.

Patients in the experimental cohort participated in 12 weeks of thrice-weekly supervised aerobic sessions on a treadmill at 85% to 95% of peak oxygen (VO2). The control group maintained their usual exercise regimen. All results were assessed in accordance with the intention-to-treat principle.

The key outcome was cardiorespiratory fitness, which was determined by peak VO2, an established surrogate marker for CVD and CVD-related deaths. VO2 was evaluated during the initial fitness baseline test, and then assessed in the postintervention period. These tests were performed on treadmills. Researchers used a modified Bruce protocol to establish the highest value of oxygen uptake among 15-second intervals.

Secondary outcomes were assessed with a blood draw 12 hours after the patients had fasted. This assessment evaluated PSA concentrations and kinetics, including PSADT and PSAV, sex hormone levels, functional fitness, and anthropometrics, as well as the proliferation of plasma prostate cancer cell line.

Unfortunately, the impact of the COVID-19 outbreak resulted in the successful completion of only 880 out of the planned 918 exercise, and postintervention assessments were completed 2 weeks earlier than planned due to the closure of public facilities.

In total, 8 participants experienced aggravated symptoms that could be related to the exercise regimen. Of those adverse events, 6 reported joint pain, 1 reported chest discomfort, and 1 reported lightheadedness. One patient experienced a stomach bleeding that was not connected to the HIIT training.

“Ultimately, the ERASE trial [was] well-constructed and demonstrates the power of a lifestyle intervention with far-reaching implications,” concluded Neha Vapiwala, MD, Department of Radiation Oncology, University of Pennsylvania, in an invited commentary on the study. “Although the specific focus on patients pursuing AS is technically not unique, it is uncommon; demonstration that HIIT alone, without dietary changes, resulted in improved cardiorespiratory fitness and biochemical parameters in men with localized PC on AS and growth inhibition at the cellular level is novel and noteworthy… the ERASE trial does empower patients with PC on AS to be in better physical, functional, and psychological shape for any future medical interventions they may need.” ²

Larger trials are still needed to determine the biophysiological connection between exercise and prostate cancer and to identify potential tumor-related biomarkers.

Future trials should seek to broaden sample size by realizing and planning for the potential recruitment bias (fit and physically active men) as well as plan for long-term follow-up to assess clinical outcomes.

References:

• Kang D, Fairey AS, Boulé NG, Field CJ, Wharton SA, Courneya KS. Effects of Exercise on Cardiorespiratory Fitness and Biochemical Progression in Men With Localized Prostate Cancer Under Active Surveillance: The ERASE Randomized Clinical Trial. JAMA Oncol. Published online August 19, 2021. doi:10.1001/jamaoncol.2021.3067
• Vapiwala N. The Power of Exercise to Influence Cardiovascular and Oncologic Outcomes—Survival of the Fittest. JAMA Oncol. Published online August 19, 2021. doi:10.1001/jamaoncol.2021.3065