A lifestyle intervention to improve outcomes in men with castrate-resistant prostate cancer

Background There is increasing evidence demonstrating that lifestyle interventions of exercise and diet may represent a useful supportive therapy for men with prostate cancer, improving physiological and psychosocial outcomes. There has been limited investigation of the effects of such interventions in men with castrate resistant prostate cancer (CRPC), the terminal phase of the disease. It is not clear how exercise has been implemented in the prostate cancer care pathway and what a successfully implemented exercise programme might look like. Furthermore, the specific treatment and disease related barriers men with CRPC might face engaging in exercise is not documented, particularly when considering their advanced stage of disease. This work described in this thesis covers an exploration of the feasibility and acceptability of an exercise and dietary intervention to improve outcomes in men with CRPC. Methods A healthcare professional survey was conducted to assess the extent to which NHS trusts are meeting the NICE guidelines (CG175, 1.4.19) for exercise training for men with prostate cancer on androgen deprivation therapy (ADT). Semi-structured interviews of UK healthcare professionals, specialising in prostate cancer care and based in UK National Health service (NHS) trusts were conducted. These explored underlying reasons behind the variability in NHS trusts in delivering exercise training programmes and probed the views of the HCPs regarding exercise training, including the acceptability of concurrent use of an anabolic agent for men with CRPC. A feasibility randomised controlled trial (RCT) of an exercise and dietary intervention in CRPC patients was conducted (COMRADE). Men with CRPC recruited to the RCT were randomised on a 1:1 ratio to either the intervention or usual care for 16 weeks. Men allocated the intervention received up to 24 three sessions of supervised resistance exercise a week; supplemented with whey protein and creatine monohydrate; and given dietary advice. They were also asked to partake in at least one independent moderate intensity aerobic activity lasting at least 30 minutes a week. Following the RCT, post study participant focus groups addressed patients’ views on aspects of the study, particularly with regards to acceptability of trial procedures, barriers and facilitators to exercise training and the impact of living with CRPC. Results The healthcare professional survey demonstrated significant variability between NHS trusts in the UK in delivering the NICE guidelines and that a supervised exercise training programme is not currently embedded within "usual care" for prostate cancer. The healthcare professional interviews (n=12) demonstrated support for an individualised and adaptable exercise programme for men with CRPC which could improve fitness and mitigate some of the long term effects of their cancer/cancer therapy. Their opinions reflected that comorbidities and disease/treatment specific barriers to exercise must be taken into account to support better adherence. In the feasibility RCT, n=31 men were recruited from a total of n=3607 screened (recruitment rate=13.6%). There were eighteen in the intervention and thirteen randomised to the control group. The attrition rate was 16%, with n=4 dropping out of the intervention and n=1 death in the control. Adherence to the supervised and independent exercise sessions was 69% and 78% respectively. The adherence to the whey protein was 68% and creatine was 71%. There were 4 AEs associated with trial procedures, none of which were serious. Three primary themes were identified from the participant focus groups (n=3); these included 1) living with CRPC, 2) experience and opinions of the trial, 3) attitudes and experiences of exercise training and physical activity. The findings demonstrated that the study procedures were well received by 25 the participants, including the trial assessments and format of the intervention. Valuable insights were gained for implementing future exercise intervention studies - providing participant perspectives for the success of a lifestyle behaviour study such as COMRADE. Conclusions The findings suggest that it is feasible to randomise and retain men with CRPC to an exercise and diet intervention, however there was a high rate of attrition in the study, due to the complex nature of the disease in these men. Further work is required to address the barriers related to implementation of exercise in the prostate cancer pathway for men with CRPC