Author Identifiers

Kim Edmunds

ORCID: 0000-0001-7379-1294

Date of Award

2021

Degree Type

Thesis

Degree Name

Doctor of Philosophy

School

School of Medical and Health Sciences

First Advisor

Professor Robert Newton

Second Advisor

Associate Professor Haitham Tuffaha

Third Advisor

Professor Daniel Gãlvao

Fourth Advisor

Professor Paul Scuffham

Abstract

Background

Androgen deprivation therapy (ADT) is associated with numerous adverse effects that impact on quality of life and contribute further to the cost burden of prostate cancer (PCa) via treatment and supportive care. Exercise medicine is effective in slowing PCa progression, reversing treatment adverse effects and improving quality of life and survival of patients, however, no economic analyses have been conducted to determine whether exercise is cost-effective in this population.

Objectives

Firstly, to examine the adverse effects of ADT for PCa and the evidence supporting the use of exercise medicine in their management. Secondly, to conduct the first economic evaluations of exercise medicine in the management of the adverse effects of ADT for PCa to strengthen the evidence base for the development of effective health policy around exercise and PCa survivorship.

Methods

A systematic review was conducted to determine the incidence of the adverse effects of ADT for PCa. A rapid review examined the role of exercise in managing these adverse effects. Three economic evaluations were then conducted to determine the cost-effectiveness of supervised exercise for men with PCa receiving ADT. Two trial-based cost-effectiveness analyses (CEAs) compared exercise training and usual care (a suggestion to exercise). The first involved a preliminary randomised controlled trial (RCT) of exercise for 20 men with metastatic PCa. A value of information (VOI) analysis was also conducted to examine the need for and value of a larger trial. The second CEA involved a RCT of exercise for men previously treated with radiation therapy and ADT. For the third economic evaluation, a decision analytic Markov model was constructed to evaluate the cost-effectiveness of an exercise intervention in preventing falls and fractures for men with localised or locally advanced PCa receiving ADT. All economic analyses were conducted from a healthcare payer perspective and the primary outcome measure was quality adjusted life years (QALYs) gained. Uncertainty in the results was explored using deterministic univariate and probabilistic sensitivity analysis where appropriate.

Results

The systematic review generated incidence evidence for nine adverse effect groups and 19 sub-groups, with statistically significant increased risks in 17 sub-groups. The rapid review revealed that exercise was effective in improving body composition, physical function and fatigue, as well as mitigating the bone loss, sexual dysfunction and psychosocial effects associated with ADT. The first within-trial CEA of exercise for men with metastatic PCa resulted in an incremental cost-effectiveness ratio (ICER) of $133,509 and a 30% probability of being cost-effective after three months at a willingness-to-pay of AU$50,000. VOI analysis suggested further research is likely to be cost-effective to conduct. The second within-trial CEA of exercise for men who received radiation therapy and adjuvant ADT for localised PCa resulted in an ICER of $64,235 and a 41 per cent probability of cost-effectiveness after six months at a willingness-to-pay of AU$50,000. For the modelled cost-utility analysis, the exercise intervention dominated usual care (a suggestion to exercise), as it was less costly and more effective. Net monetary benefit (NMB) was $102,112 and probabilistic sensitivity analysis showed a 58% probability of cost-effectiveness at a willingness-to-pay of AU$50,000.

Conclusion

This research is the first to examine the cost-effectiveness of exercise for men with PCa receiving ADT. Supervised exercise is effective in managing many adverse effects of PCa treatment and cost saving in preventing falls and fractures. Future efforts need to focus on strengthening the evidence base in exercise for ADT adverse effect management. Uncertainty in economic evaluation can be reduced with more comprehensive cost and outcome data, longer follow up and larger sample sizes. This research has the potential to translate into changes in clinical practice, better informed policy decisions, cost savings for healthcare payers, and ultimately, better health and quality of life for PCa patients, survivors and their families.

Available for download on Friday, April 22, 2022

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