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 1:1 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