Exercise during Active Surveillance for Prostate Cancer: The ERASE Trial

• Author / Creator

  Kang, Dong-Woo

• Background: Prostate cancer treatments often lead to side effects including sexual and urinary dysfunction as well as fatigue and poor quality of life. As a means of avoiding these side effects, active surveillance has been introduced as a strategy to manage men with low- to moderate-grade prostate cancer. In active surveillance, treatments are delayed until the prostate cancer becomes clinically significant. Despite the advantages of active surveillance, many men still require radical treatments eventually, have a higher risk of metastasis, and experience psychosocial distress. Interventions that slow the progression of the disease, manage anxiety and fear of cancer progression, and better prepare men for impending radical treatments would be highly beneficial. Exercise delays the progression of prostate tumours in animal models through alterations in immune function; however, these findings have not been confirmed in men with prostate cancer. Moreover, exercise improves quality of life in prostate cancer patients during and after radical treatments but no study to date has focused on men with prostate cancer on active surveillance or examined fear of cancer progression. Finally, exercise may serve as a prehabilitation strategy in the oncology setting but no study to date has examined fitness outcomes that may be associated with posttreatment recovery in men with prostate cancer on active surveillance.
  Purpose: The primary purpose of this dissertation was to examine the effects of exercise on cardiopulmonary fitness as a surrogate marker of prostate cancer outcomes, patient-reported outcomes, and posttreatment complications in prostate cancer patients on active surveillance. Secondary aims were to examine the impacts of the intervention on cancer-related biomarkers, physical fitness, and psychosocial outcomes.
  Methods: This study was a phase II randomized controlled trial in 52 men with localized prostate cancer undergoing active surveillance. Participants were randomly allocated to either high-intensity aerobic interval exercise (HIIT, n=26) or usual care (UC, n=26). The primary outcome was cardiopulmonary fitness. Secondary outcomes included cancer-related biomarkers, patient-reported psychosocial outcomes and cancer-related symptoms, and physical and functional fitness.
  Results: Participants were recruited from July 2018 to February 2020. Overall, 361 men with PCa undergoing AS were screened, 176 (51%) were eligible, and 52 (30%) were randomized with 26 participants per group. There were two dropouts from the HIIT group (unwillingness; medical issue) and one from the UC group (no contact). A total of 46 participants (88%) completed the postintervention VO2peak assessment and 49 (94%) completed the postintervention functional fitness assessment and blood draw. The primary outcome of VO2peak significantly improved in the HIIT group compared to the UC group (adjusted between-group mean difference, 1.6 ml·kg-1·min-1; 95% confidence interval [CI], 0.3 to 2.9; p=0.014). HIIT also exerted a significant reduction in PSA levels (adjusted between-group mean difference, -1.1 ug/L; 95% CI, -2.1 to 0.0; p=0.043) and PSA velocity (adjusted between-group mean difference, -1.3 ug·L-1·year-1; 95% CI, -2.5 to -0.1; p=0.040). There were significant improvements in cardiometabolic and inflammatory markers including total cholesterol (p=0.011), non-HDL-C (p=0.006), IL-1β (p=0.006), IL-4 (p=0.017), and IL-12p70 (p=0.009) and psychological outcomes including prostate cancer-specific anxiety (p=0.024) and fear of cancer progression (p=0.013), hormonal symptoms (p=0.005), perceived stress (p=0.037), fatigue (p=0.029), and self-esteem (p=0.007).
  Conclusions: HIIT improved cardiopulmonary fitness, biochemical progression of prostate cancer, systemic lipid and inflammatory markers, and prostate cancer-specific anxiety. These findings suggest clinical benefits of HIIT in active surveillance setting such as delaying radical treatment through suppressing prostate cancer progression and addressing fear of cancer progression. Also, the improvement of cardiopulmonary fitness may prepare these men for possible radical treatment. Larger phase II/III trials are warranted to confirm the longer-term clinical benefits of exercise in the active surveillance setting.

• Subjects / Keywords

  • Exercise
  • Prostate cancer
  • Randomized controlled trial

• Graduation date

  Spring 2021

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/r3-aenh-x546

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.