Design: A study comparing less-invasive partial ablation (PA) of the prostate with standard total ablative surgery in the form of radical prostatectomy (RP). The study will be conducted in two phases: Phase 1, a feasibility phase (HTA funding already secured) followed by Phase 2, the main recruitment phase. Currently funding is secured for Phase 1 of the PART study only. Setting: Phase 1: Four large Urology departments at Oxford, Sheffield, Bristol and UCLH with the appropriate skill mix. Target Population: Men with localised prostate cancer amenable to PA of the prostate or RP. Inclusion Criteria: Men with unilateral clinically significant intermediate risk prostate cancer or dominant unilateral clinically significant intermediate risk & small contralateral low-risk disease: - Gleason grade score 7 (3+4 or 4+3) - High volume Gleason grade score 6 (> 4mm cancer core length) - PSA = 20 ng/ml - = T2b disease Life expectancy of =10 years Fit, eligible and normally destined for radical surgery No concomitant cancer No previous treatment of their prostate cancer An understanding of the English language sufficient to understand written and verbal information about the trial, its consent process and the study questionnaires Health Technology Being Assessed Phase 1 of the PART study will assess the feasibility of identifying and randomising men with unilateral intermediate risk CaP to a RCT comparing RP with PA using minimally invasive technology. Phase 1 will also assess the treatment effectiveness and cost-effectiveness of total surgical versus partial prostate ablation using High Intensity Focal Ultrasound (HIFU). HIFU is a rapidly evolving technology currently being introduced and taken up widely across the NHS without robust evidence about their utility or effectiveness. The aim of PA is to target and treat only the part of the gland harbouring significant cancer. This should minimize morbidity by reducing the principal adverse surgical sequelae of erectile dysfunction and urinary incontinence. Whilst evidence exists from non-randomised Phase I and II trials, these technologies are untested in intermediate risk disease in the context of comparative RCTs. NICE recommends that minimally ablative techniques should only be used with special arrangements for clinical governance, consent and audit or research. The findings of the HTA systematic review 10/136/01: Ablative therapy for men with localised CaP, which is due to publish shortly, conclude that the role of focal therapies in the management of men with localised CaP should be investigated. It may be desirable to incorporate the focal approach into a multicentre RCT, with long-term follow-up and would include predefined assessment of cancer-specific, dysfunction and health-related quality of life measures. Our hypothesis is that a significant proportion of these patients would benefit from focal therapy with minimally invasive rather than radical procedures, with less morbidity, improved QoL, and reduced cost without compromising treatment effectiveness. If this can be established, ablative procedures could eventually replace conventional radical treatments in suitable patients and reduce the burden of treating the disease for the patients and the NHS. Selection of Outcome Measures The most relevant outcome for comparing PA with RP is CaP mortality. We know from previous studies that the benefits of RP compared to active monitoring appear modest and take at least 10 years to emerge. Further data on disease-specific mortality following conventional treatment options will be available when we report our ProtecT study primary outcome at 10-year median follow-up. So, given that differences between partial and radical procedures are likely to be smaller, this would require a 15 or 20-year study including several thousand patients for reliable results. Though such a study would be desirable, our current proposal is for an 18 month feasibility study, which, if successful, may progress to a 5-year study (Phase 2) addressing the key short-term unknowns that will provide important new information to assist patients and health care providers make informed decisions on the complex benefits and risks of partial compared to radical surgery. Selection of Comparator We have selected RP as the comparator for a number of reasons: firstly, evidence to date suggests no significant differences in oncological outcomes between radical treatment options; secondly, surgery will allow careful pathological staging to be performed in the radical arm, which with randomisation should mirror the composition of the minimally intervention cohort; thirdly, criteria of treatment failure are easy to apply following surgery; fourthly, secondary treatment after failure (adjuvant radiotherapy) will be the same in both arms. Measurement of Costs and Outcomes PHASE 1: Primary Objective - Testing the feasibility of a randomised trial of PA using energy-delivery based technologies versus RP (surgical comparator) for intermediate risk unilateral prostate cancer. Primary Outcome measures - Randomisation of 100 participants within the proposed timelines - Uptake of consent & randomisation of =50% among invited, eligible patients. Secondary Objectives - Qualitative Recruitment Investigation (QRI) to understand recruitment challenges for this trial and inform optimal recruitment strategies for Phase 2 of the PART study. - To collect data on quality of life and resource usage and inform power calculations for Phase 2 of the PART study. - To explore methods and feasibility of data capture instruments to inform power calculations and health economic evaluation for Phase 2 of the PART study. Secondary Outcome measure - Findings of the Qualitative Recruitment Investigation (QRI). PHASE 2: Primary Objective - To compare treatment failure rates between the two treatment groups. Primary Outcome measure - Primary treatment failure as demonstrated by the need for whole gland ablation and/or secondary radiotherapy Secondary Objectives - To compare the short, medium and long-term effects of both treatment arms - The effect on Quality of Life and Health Resource Utilisation of both treatment arms - The role of imaging by mpMRI and biopsy protocols in determining suitability of patients for focal therapy Secondary Outcome measures - Short, medium and long-term?adverse events related to treatments - Disease progression including development of metastases - Disease-specific and all-cause mortality - Quality of life using conventional questionnaires (IIEF-15, IPSS, EQ-5D-5L, FACT-P, UCLA-EPIC) - The role of imaging by mpMRI and biopsy protocols in determining the suitability of patients for focal therapy using data collected in the CRF. Sample Size/Project Timetable Phase 1: 18-month feasibility phase aiming to achieve a minimum 50% randomization with an estimated 100 men recruited in 4 centres starting in January 2015.
- Centre for Surgical Research