The ELIPSE Study - a randomised controlled trial comparing the clinical and cost-effectiveness of lymph node removal in patients undergoing curative surgery for localised high-risk prostate cancer.

Research Question Does PLND provide better cancer control compared to no PLND in patients undergoing surgery for localised high-risk PCa? Aims and Objectives To compare the clinical and cost effectiveness of PLND versus no PLND in clinically localised high-risk PCa patients undergoing radical prostatectomy (RP) surgery. 1. Primary objectives: Compare RP+ PLND and RP alone in terms of cancer recurrence and cost-effectiveness at 3 years. 2. Secondary objectives: Compare safety, complete excision of primary prostate tumour, other cancer outcomes, continence and potency, and generic health related quality of life (HRQOL). Model the cost-effectiveness over the lifetime of patients, using data from the trial supplemented with published long-term data. Methods: Design: Two-arm multicentre pragmatic superiority RCT. Health technologies being assessed: Robot assisted laparoscopic radical prostatectomy (RP) with and without PLND. PLND involves excision of lymph glands from standard pre-defined anatomical locations in the pelvis – external iliac, obturator and internal iliac territories. Target population: 25 NHS centres routinely offering surgery for localised high-risk PCa. Inclusion Criteria: Adults (age >18 years) with new localised high-risk PCa; multi-disciplinary review confirming suitability for surgery (RP); conventional staging imaging, Gleason Grade = 4+3=7 or PSA >20 or stage T3. Exclusion Criteria: Previous hormone therapy, previous PCa treatment, unsuitable for surgical treatment. Outcome measures: 1. Primary outcome: Time to cancer recurrence, defined as: PSA recurrence/persistence with two consecutive measures >/= 0.2ng/ml (American & European Urology guidance) OR disease progression (e.g. metastatic disease) OR need for further PCa treatment OR PCa specific death. 2. Secondary measures: - incremental cost per QALY gained with PLND versus no PLND, modelled over the estimated lifetime of patients using trial data, health care resource use and HRQoL - complications - positive surgical margins, - cancer outcomes (progression free survival, metastasis free survival, PCa-specific mortality) - HRQoL using a prostate specific questionnaire, EPIC 26 (15), and EQ-5D-5L collected at baseline, then 3, 12, 24, and 36 months post-surgery. 3. Longer-term follow-up: We will obtain consent from participants to allow future follow-up through efficient means (such as routine data) as part of a separately funded study. Sample size: We will recruit 1080 participants to detect a 10% or more difference in RP + PLND vs RP alone at three years with 90% power and 5% significance assuming 10% loss to follow-up. Timelines for delivery: Start date: 1 Nov2023; Study duration: 72 months; 6 months for study set up, 24-month recruitment, 36-month follow-up for all participants, and 6 months for site close-down and analysis and writing up. Impact and dissemination : Having carefully identified clinician and patient equipoise, outcomes from this study targeting these specific areas of clinical uncertainty will be impactful in informing day-to-day practice. Clinical and cost-effectiveness results will be presented in high-impact journals and conferences. With our PPI team we will produce lay summaries and disseminate through patient organisations (PCUK and The Urology Foundation (TUF) websites), and social media. We will inform policy makers shaping NHS practice, such as NICE, NHS England and international guideline writing committees.