Title

Exercise as adjunct therapy during treatment for men with prostate cancer

Author Identifiers

Oliver Schumacher https://orcid.org/0000-0002-8814-9429

Date of Award

2022

Degree Type

Thesis

Degree Name

Doctor of Philosophy

School

School of Medical and Health Sciences

First Advisor

Robert Newton

Second Advisor

Daniel Galvão

Third Advisor

Dennis Taaffe

Abstract

Background: Radiation and hormone therapy, either alone or in combination, are standard treatments for prostate cancer that improve patient outcomes. However, they are associated with significant adverse effects that can impact quality of life. Moreover, a substantial number of patients will experience disease recurrence that may require further treatment, resulting in additional side effects. Exercise medicine has been identified as a potential strategy to mitigate treatment-related toxicities. In addition, results from preclinical studies indicate that exercise can modulate the tumour microenvironment and thereby improve radiotherapy treatment efficacy. However, most exercise studies for men with prostate cancer have either been conducted in patients on hormone therapy or in relation to surgery and there is a dearth of knowledge regarding the potential benefit of exercise during radiotherapy. Furthermore, there are no published studies that have investigated and confirmed the acute tumour modulatory effect of exercise in a clinical population.

Purpose: The purpose of this doctoral research was to explore the utility of exercise as an adjunct therapy for prostate cancer patients undergoing treatment, with a particular focus on radiotherapy and the implementation of exercise programs into standard clinical care pathways.

Methods: This thesis comprises three interrelated parts. Part 1 is a systematic review with meta-analysis and a secondary data analysis of two randomised controlled trials where the effects of exercise on physical function as well as treatment-related side effects in men with prostate cancer during radiotherapy were investigated. In Part 2, I discuss the potential role of exercise to improve the response to radiotherapy in prostate cancer patients through modulation of tumour perfusion and oxygenation. Furthermore, I investigate the effect of an acute bout of 10-15 minutes of moderate-to-vigorous-intensity step exercise on tumour perfusion using magnetic resonance imaging. Finally, in Part 3, I assess the feasibility of aerobic and lower-body resistance exercise training immediately before radiotherapy fractions in men with prostate cancer undergoing 4-8 weeks of external beam radiation therapy and expand on the notion of treatment-integrated delivery of exercise programs. The latter comprises an analysis of a nationwide industry-led community-based patient support initiative for men with locally advanced, relapsed or metastatic prostate cancer receiving Lucrin® – The Man Plan® Program.

Results: In Part 1, we found exercise to be an effective intervention to mitigate urinary toxicity and fatigue during radiotherapy for prostate cancer. Furthermore, multimodal exercise resulted in significant improvements in cardiorespiratory fitness and upper and lower-body muscle strength. In Part 2, there was preliminary evidence for exercise to acutely increase tumour perfusion in men with prostate cancer. Moreover, the results in Part 3 support the feasibility of treatment-integrated, pre-radiotherapy exercise training for prostate cancer patients. Additionally, the investigation revealed that The Man Plan® Program is an effective intervention to prevent weight gain, reduce blood pressure and improve physical function.

Conclusions: Exercise is an effective strategy to improve physical function and manage treatment-related toxicity in prostate cancer patients undergoing radiation and hormone therapy. Furthermore, the findings from this thesis provide new insights into the potential impact of exercise on the tumour microenvironment.

Access Note

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