Neurovascular structure-adjacent frozen-section examination vs. standard robot-assisted radical prostatectomy: a systematic review and meta-analysis of two-arm comparative studies on functional and oncological outcomes

Abstract

The precise balance between nerve preservation and tumor control during robot-assisted prostatectomy remains a clinical challenge. The NeuroSAFE technique can guide secondary resection through intraoperative real-time frozen pathology, but its overall value for perioperative safety and oncological and functional prognosis is still a matter of debate. The objective of this study was to carry out a systematic evaluation of the impact of NeuroSAFE technology on perioperative safety and functional and oncological outcomes. In accordance with the PRISMA guidelines, a comprehensive search of the PubMed, Web of Science, and Cochrane Library databases was conducted, with a cutoff date of April 2025. NeuroSAFE technology was comprehensively evaluated from the perspectives of oncology, functionality, and perioperative safety. This meta-analysis included 14 studies (2 randomized controlled trials, 12 non-randomized studies; sample size = 26,442), in which a total of 14,458 patients underwent NeuroSAFE robot-assisted radical prostatectomy (RARP) and 11,984 patients underwent standard RARP. NeuroSAFE significantly reduced the rate of positive surgical margins (OR: 0.59, 95% CI: 0.59-0.87, p < 0.001) and the PSA persistence rate (OR: 0.52, 95% CI: 0.05-5.64, p < 0.05) while also reducing the 2-year biochemical recurrence rate (OR: 0.81, 95% CI: 0.45-1.45). The functional outcomes revealed that NeuroSAFE demonstrated superiority in preserving the neurovascular bundle (OR: 3.86, 95% CI: 1.56-9.58, p < 0.001) and improving postoperative erectile function (OR: 2.40, 95% CI: 1.65-3.50, p < 0.05) but no significant advantage in urinary control (OR: 1.49, 95% CI: 1.07-2.09, p > 0.05). During the perioperative period, NeuroSAFE prolonged the surgical time (mean difference: + 22.84 min, p < 0.001) but did not increase the incidence of serious adverse events (3% vs. 3% SAEs). Rare complications included, among other events, one death due to cecal rupture. Our meta-analysis confirmed that the NeuroSAFE technique offers advantages over standard RARP in terms of tumor control, functional preservation, and nerve preservation rates without increasing the incidence of severe postoperative adverse events. Although this technique prolongs the surgical time, its overall advantages are evident. Its long-term efficacy and safety require validation through multicenter, large-sample randomized controlled trials.

Keywords: Da Vinci; Meta-analysis; NeuroSAFE; Prostate cancer; Standard robot-assisted radical prostatectomy.