NeuroSAFE PROOF. Update on a multi-centre, pragmatic, RCT for men undergoing robot-assisted radical prostatectomy: Trial in progress

ABSTRACT

Introduction & Objectives: Robot-assisted Radical Prostatectomy (RARP) is an effective cure for organ confined prostate cancer but is associated with considerable post-operative functional toxicity. The NeuroSAFE technique (intra-operative frozen section analysis of the neurovascular structure adjacent margin) may help improve functional outcomes by promoting optimal nerve-sparing (NS) RARP without compromising on oncological outcomes. NeuroSAFE technique has reported favourably in retrospective, single-centre studies but has never been evaluated prospectively by a randomised study. The NeuroSAFE PROOF Feasibility Study has succeeded in demonstrating feasibility and has been succeeded by the fully powered, definitive NeuroSAFE PROOF Randomized Controlled Trial (RCT) (NCT03317990). Materials & Methods: Potent men (IIEF-5>21) with localised prostate cancer at 4 regional uro-oncology centres in the UK (UCLH, Bristol, Sheffield and Glasgow) are eligible. Participants are randomised 11 to RARP with NS decision guided by standard of care (clinical information, DRE and pre-operative mpMRI surgical plan) vs. RARP with NS decision guided by standard of care information and the NeuroSAFE technique. The primary outcome is erectile function (EF) recovery assessed by IIEF-5 score at 12-months. Important secondary outcomes include detailed peri-operative outcomes, histological outcomes, post-operative complications, biochemical recurrence rates, urinary continence (assessed by ICIQ), health related quality of life (assessed by Rand-36 and EQ-5D-5L), and health economics. In order to demonstrate a difference of 15% in EF recovery rates between the arms, a total of 404 men will be randomised and treated. Patient follow-up will continue for 5 years after RARP. Results: At the time of writing, 160 men have been recruited and treated with RARP as per random allocation at 4 participating sites. The independent DMC has met twice to ensure the oncological safety of the trial and will continue to review the data at intervals. Covid-19 has led to significant challenges, including suspension of recruitment and difficulties performing follow-up. The trial team have developed new methods of recruitment, consent and follow-up to ensure conduct of the study remains in line with the highest standards of trial conduct, including electronic remote consent processes and remote collection of PROMs. Conclusions: The NeuroSAFE technique has been reported as a method to optimise outcomes for men undergoing RARP for over a decade, but, in the absence of Level 1 evidence, equipoise remains. Despite the Covid-19 pandemic recruitment continues to be favourable. We hope that our