A randomised controlled trial of Partial prostate Ablation versus Radical Treatment (PART) in intermediate risk, unilateral clinically localised prostate cancer

Background: Prostate cancer (PCa) is the most common cancer in UK men. Patients with intermediate-risk, clinically localised disease are offered radical treatments such as surgery or radiotherapy, which achieve good disease control but can result in urinary, bowel, and sexual side effects. Alternative partial ablation (PA) technologies are being introduced that have fewer such side-effects, however, their effectiveness compared to radical treatments has not been evaluated rigorously. The applicants have completed a feasibility study [HTA - 12/35/54] and now propose to undertake a full randomised controlled trial (RCT). Objectives: To assess the clinical and cost-effectiveness of PA versus the standard radical treatments currently available on the NHS (i.e. radical prostatectomy [RP], radical radiotherapy [RRT] and low dose-rate brachytherapy [LDR-B]) for unilateral intermediate-risk PCa; and to provide high-quality evidence on the comparative benefits and risks of these treatment options in terms of oncological outcome and quality of life (QoL). Design: A prospective, multi-centre RCT incorporating an integrated QuinteT Recruitment Intervention (QRI) to understand, monitor and address barriers to participation. The setting will be 10 or more large Urology departments in NHS hospitals. 800 men with intermediate-risk unilateral clinically localised PCa will be randomised to radical treatment or PA. Follow-up will be conducted using standard NHS care protocols for the radical treatment group, and a combination of multi-parametric Magnetic Resonance Imaging (mpMRI) and repeat targeted or systematic prostate biopsies in the PA group. Outcome measures: The co-primary outcome will be 1) treatment failure (defined using conventional criteria in the radical treatment group, and the indication of need for whole gland treatment in the PA group), and 2) QoL assessed using the Patient Oriented Prostate Utility Scale (PORPUS-P) questionnaire. Secondary outcomes include cost-effectiveness, further QoL measures assessed using validated PROMs questionnaires, disease progression, PCa-specific death, and all-cause death. Methods: The feasibility study demonstrated that the full RCT is possible and highlighted design modifications (e.g. adding radiotherapy as a radical treatment option, providing the PA treatment free-of-charge) that should facilitate recruitment. Participants will be recruited following identification at Urology departments’ Multidisciplinary Team meetings. Treatment failure will be compared using survival analysis techniques according to the intention-to-treat principle. QoL analyses will use mixed models for repeated measures. Timelines for delivery: Set up and start of recruitment by Q4Y1, complete embedded pilot phase by Q2Y3, complete recruitment Q4Y6, and report Y7 with approximately 3 years’ median follow up. Anticipated impact and dissemination: This RCT will provide the first high-quality data on the comparative benefits and risks of PA and radical treatment in the management of unilateral intermediate-risk PCa. The findings will inform decision-making for commissioners, clinicians and patients with this common disease by determining the trade-off between these treatment options. Dissemination will be through publications, presentations and other media. A full Patient and Public Involvement programme is included.