Title: A randomised controlled trial of Partial prostate Ablation versus Radical Treatment (PART) in intermediate risk, unilateral clinically localised prostate cancer
Funder: Department of Health and Social Care

Abstract: Aims of the research: _x000D_ To test whether partial treatment of the prostate is as effective in curing prostate cancer as treatment of the whole prostate by surgical removal or radiotherapy (known as ‘radical’ treatments), with fewer side-effects. This will ensure that patients have access to new, critical information about the 'trade-off' between cancer control and side-effects following each treatment option. This will guide decision-making for doctors and patients in future._x000D_ _x000D_ Background to the research: _x000D_ Prostate cancer is the most common cancer in UK men. Some men have cancer on one side of the prostate, but are still offered treatment to the whole prostate. New technologies can now treat part of the prostate only, destroying the cancer but preserving urinary and sexual functions. These technologies may have fewer side-effects, but none has been compared with radical treatments to ensure they are as safe and effective. _x000D_ _x000D_ Design and methods used: _x000D_ We will identify 800 suitable men in 15 UK centres with cancer on one side of the prostate only, and invite them to join the study. If they agree, after receiving full study information, they will be randomly allocated to have a radical treatment (choice of surgery or radiotherapy), or partial treatment. All patients will be assessed regularly to check if the treatments have worked, using blood tests and imaging, and repeat biopsies for the men who receive partial treatment. If there is any sign of the disease returning or worsening, additional treatments will be discussed and offered. We will compare how well the treatments work by measuring the time it takes for additional treatment to be necessary in the radical treatment arm, or to require treatment of the whole prostate in the partial treatment arm. We will also assess quality of life using questionnaires, and costs to the NHS of each treatment._x000D_ _x000D_ Patient and public involvement (PPI): _x000D_ We consulted PPI representatives in the pilot (preliminary) study. Our PPI representatives helped design the pilot and this main proposal, and will help to monitor study progress. The pilot study PPI representatives have agreed to continue to advise us in the main study._x000D_ _x000D_ Dissemination: We will share our results when they become available by publishing papers in scientific journals, making presentations at national and international meetings, and informing the media as appropriate and as advised by our PPI representatives.

Lay abstract: 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)._x000D_ 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)._x000D_ 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. _x000D_ 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. _x000D_ 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._x000D_ 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._x000D_ 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.

Research activity codes: 6.4 SURGERY;6.5 RADIOTHERAPY AND OTHER NON-INVASIVE THERAPIES
Health categories: CANCER AND NEOPLASMS