Title: Supported exercise TrAining for Men with prostate caNcer on Androgen deprivation therapy - STAMINA
Funder: Department of Health and Social Care

Abstract: Aim To determine whether either a specific behaviour-change informed, supervised exercise intervention (STAMINA) with support embedded in existing standard NHS prostate cancer (PCa) care pathways over 12 months will confer long-term benefits in cancer-specific quality of life (QoL) and fatigue for men on androgen deprivation therapy (ADT) and be cost-effective, compared with usual care. Background and rationale ADT for advanced PCa has debilitating adverse effects that impair QoL. ADT increases the risk of diabetes and cardiovascular disease, which are expensive to treat. The NICE PCa guidelines (CG175) recommend 12-weeks supervised exercise-training for men on ADT to improve cancer-specific QoL and fatigue. There is no current understanding of how to integrate such interventions into NHS care, sustain benefits or of cost implications. Research plan The programme consists of five work-packages (WPs), each building on our programme development grant (PDG) work and on preceding WPs. WP 1: understanding variations in NHS PCa-care pathways and exercise provision for men on ADT. Building on information gained in our PDG, we shall interrogate the provision of prostate cancer (PCa) care and exercise facilities for men started on ADT at participating NHS sites to pinpoint optimal opportunities for patient-professional interactions to maximise exercise behaviour change. Methods Online survey of healthcare professionals (HCPs) to determine touch-points of care and training preferences, parallel mapping of exercise facilities and exercise professional (EP) expertise and extent of communication between HCPs and EPs. Schematics will inform intervention and process evaluation development for WP2, WP3 and WP5. Where sites are allocated to control, these schematics will be used to define usual care. WP2 and WP3: develop, optimise and test STAMINA service-level intervention. Methods Map PDG qualitative findings to behaviour change theory. Develop behaviour-change interventions in partnership with patients, HCPs and EPs via focus groups and workshops (WP2). Pre-pilot (WP3). The core STAMINA intervention will be delivered at affiliated Nuffield Health (NH) to 32 men from up to four NHS-sites followed by a mixed-methods process-evaluation (PE) of process data (e.g. training package use, recruitment, retention, adherence) for fidelity and acceptability. The health economics team will be involved throughout intervention design to identify resource implications and unit costs to minimise intervention costs, increasing the likelihood of financial viability. WP 4: Evaluate effectiveness and cost-effectiveness between STAMINA and usual care in a cluster-randomised trial (cRCT) and discrete choice experiment (DCE) exploring alternative funding arrangements. Methods Three-arm, cluster randomised controlled trial in 40 UK NHS sites randomised to STAMINA or usual care (1:1) in men with prostate cancer on ADT, incorporating an internal pilot phase to ensure acceptable recruitment, follow-up and intervention adherence rates. Sample size: 20 sites per arm (mean = 25 per site, Total = 1000), provide 90% power to detect an effect size of 0.33 for the primary outcome (8-point difference on FACT-P, assuming maximum SD of 24) at 5% significance level, an ICC of 0.05, coefficient of variation of 0.3 and assuming 25% loss to follow-up. Main trial analysis: Primary intention-to-treat analysis comparing QoL (FACT-P) between trial arms, using mixed effects linear regression, with participants nested within hospitals, and with hospitals treated as a random intercept, adjusting for participant and hospital-level covariates. Primary end-point in the economic evaluation will be cost per incremental quality-adjusted life year (QALY). A Discrete Choice Experiment will generate estimates of men s demand and willingness to pay for an extended exercise programme. WP5: process evaluation of the RCT Methods Mixed-methods likely to include rating according to validated scale of audio recording of purposively sampled, patient-facing events of the STAMINA intervention. Men (and carers) will be interviewed at different stages after delivery of the two interventions with some interviews from the usual care arm also. Quantitative data to describe intervention delivery from HCPs, EPs and participants will be analysed using descriptive statistics. Projected outputs and dissemination plans Pre-pilot, pilot and main trial participants will be sent updates in a newsletter during the trial. The peer-reviewed main RCT analysis will be sent to all participating centres, participants, NICE, professional organisations and CCGs. Presentations at national and international conferences, open access peer-reviewed publications targeting journals with wide readership, high esteem and impact factors metrics (e.g. NEJM, Lancet, BMJ). With consent from participants we plan to make anonymised data freely accessible to other research groups. We will provide national cancer charities with consultation and de-briefing e.g. Macmillan and PC-UK. Benefits to patients and the NHS Improving QoL is a stated DoH priority in 'Achieving world-class cancer outcomes for England'. If we can demonstrate benefit, we will have high quality evidence of the clinical-effectiveness and cost-effectiveness of embedding a service-level intervention into core NHS PCa care. This will be a world-first with likely transferable learning to services where preliminary evidence of benefits from exercise exists (e.g. breast and bowel cancer).

Lay abstract: A genuine opportunity exists to improve the quality of life of men with prostate cancer on ADT (castration using hormones) but robust real-world research is crucial to inform NHS practice. The National Institute of Health and Care Excellence recommends supervised weight-training combined with aerobic exercise as the evidence-based supportive treatment that combats loss in quality of life caused by ADT. Preliminary work from our development grant shows that few centres have established adequate provision for such supervised exercise according to this recommendation. Men currently on ADT inform us they would welcome exercise with support embedded in their standard prostate cancer care rather than as an add-on. We propose a system-level change in care-delivery for this common long-term condition. We shall develop and test the feasibility and safety of a training package aimed at the usual cancer care team to endorse, prescribe and support an individually-tailored, supervised weight-training and aerobic exercise programme in community-based gym facilities. Prostate cancer is as common as breast cancer. Half of all prostate cancer men receive ADT. This currently affects approximately 125,000 men every year. This is likely to increase as the population ages, to 200,000 and 300,000 in 2020 and 2030 respectively. Notwithstanding unquestioned anti-cancer benefits, ADT causes deterioration in quality of life with side-effects of hot flushes, severe tiredness and sexual problems. ADT also increases the risks of dementia, diabetes and heart disease. Some ADT side-effects, including fatigue, mimic recurrent cancer and cause understandable concern, leading to unnecessary consultations/tests. Many treatments are suggested for these side-effects, but supervised exercise is the only supportive treatment proven to improve disease-specific quality of life in these men. Short-term improvements have been demonstrated when delivered by specialist staff in non-NHS research centres, but these benefits dissipate without ongoing support. Finding ways of getting men on ADT to take up and continue exercising is essential to reduce side-effects and deliver sustained benefits. We propose embedding an exercise programme for men on ADT into prostate cancer treatment. This involves training cancer team members to endorse and support exercise, community-based specifically trained gym professionals to deliver supervised exercise and communication between them to provide seamless patient care. We shall examine whether 12 months of supervised exercise with support from the clinical team provides better value for money than current treatment in improving quality of life and reducing side-effects of castration. Our work will demonstrate whether the STAMINA intervention is beneficial, cost-effective and acceptable to patients and clinicians compared with usual care. This model would offer an improved standard of care for men with prostate cancer and provide a blueprint for integration of exercise into other cancer services. If value for money is demonstrated, it would provide evidence for NHS service roll-out.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS
Health categories: CANCER AND NEOPLASMS