A randomized controlled trial of an exercise intervention targeting cardiovascular and metabolic risk factors for prostate cancer patients from the RADAR trial

Background: Androgen deprivation therapy leads to a number of adverse effects including deterioration of the musculoskeletal system and increased risk factors for cardiovascular and metabolic complications. The purpose of this study is to determine the effects, efficacy, retention and compliance of a physical exercise intervention in a large established cohort of prostate cancer patients from the Randomised Androgen Deprivation and Radiotherapy (RADAR) study. Specifically, we aim to compare short- and long-term effects of a prostate cancer-specific supervised exercise program to a standard public health physical activity strategy utilizing printed resources on cardiovascular and metabolic risk factors. Our primary outcomes are cardiorespiratory capacity, abdominal obesity, and lipid and glycemic control, while secondary outcomes include self-reported physical activity, quality of life and psychological distress. Methods/Design: Multi-site randomized controlled trial of 370 men from the RADAR study cohort undergoing treatment or previously treated for prostate cancer involving androgen deprivation therapy in the cities of Perth and Newcastle (Australia), and Wellington (New Zealand). Participants will be randomized to (1) supervised resistance/aerobic exercise or (2) printed material comprising general physical activity recommendations. Participants will then undergo progressive training for 6 months. Measurements for primary and secondary endpoints will take place at baseline, 6 months (end of intervention), and at 6 months follow-up. Discussion: This study uses a large existent cohort of patients and will generate valuable information as to the continuing effects of exercise specifically targeting cardiovascular function and disease risk, insulin metabolism, abdominal obesity, physical function, quality of life and psychological distress. We expect dissemination of the knowledge gained from this project to reduce risk factors for the development of co-morbid diseases commonly associated with androgen deprivation therapy such as cardiovascular disease, obesity, metabolic disease and diabetes, as well as improvements in physical and functional ability, and quality of life

Can exercise ameliorate treatment toxicity during the initial phase of testosterone deprivation in prostate cancer patients? Is this more effective than delayed rehabilitation?

Background: There has been substantial increase in use of androgen deprivation therapy as adjuvant management of prostate cancer. However, this leads to a range of musculoskeletal toxicities including reduced bone mass and increased skeletal fractures compounded with rapid metabolic alterations, including increased body fat, reduced lean mass, insulin resistance and negative lipoprotein profile, increased incidence of cardiovascular and metabolic morbidity, greater distress and reduced quality of life. Numerous research studies have demonstrated certain exercise prescriptions to be effective at preventing or even reversing these treatment toxicities. However, all interventions to date have been of rehabilitative intent being implemented after a minimum of 3 months since initiation of androgen deprivation, by which time considerable physical and psychological health problems have manifested. The pressing question is whether it is more efficacious to commence exercise therapy at the same time as initiating androgen deprivation, so treatment induced adverse effects can be immediately attenuated or indeed prevented.Methods/design: We are proposing a multi-site randomized controlled trial with partial crossover to examine the effects of timing of exercise implementation (immediate or delayed) on preserving long-term skeletal health, reversing short- and long-term metabolic and cardiovascular risk factors, and supporting mental health in men receiving androgen deprivation therapy. 124 men who are about to initiate androgen deprivation for prostate cancer will be randomized to immediate or delayed groups. Immediate will commence a 6-month exercise program within 7-10 days of their first dose. Delayed will receive usual care for 6 months and then commence the exercise program for 6 months (partial cross-over). Immediate will be free to adopt the lifestyle of their choosing following the initial 6-month intervention. Measurements for primary and secondary endpoints will take place at baseline, 6 months and 12 months.Discussion: This project is unique as it explores a fundamental question of when exercise implementation will be of most benefit and addresses both physical and psychological consequences of androgen deprivation initiation. The final outcome may be adjunct treatment which will reduce if not prevent the toxicities of androgen deprivation, ultimately resulting in reduced morbidity and mortality for men with prostate cancer.Trial registration: ACTRN12612000097842