Neurovascular Structure-adjacent Frozen-section Examination (NeuroSAFE) During Radical Prostatectomy: A Systematic Review and Meta-analysis

Background and objective

A standardized intraoperative frozen section analysis of the prostate resection margin adjacent to the neurovascular bundle according to the NeuroSAFE technique is performed to maximize nerve sparing during radical prostatectomy (RP) for prostate cancer (PCa). The aim of this review was to analyze oncological and functional outcomes of NeuroSAFE.

Methods

A systematic search of the Medline, Embase, and Web of Science databases until July 2024 was performed. Studies were eligible if these included men undergoing RP with NeuroSAFE for PCa, and reported on oncological and/or functional outcomes. A cumulative analysis with random-effect models for oncological outcomes was conducted using Review Manager software, together with a narrative analysis of the procedure and functional outcomes.

Key findings and limitations

We analyzed 14 studies with nine distinct patient populations; 7505 out of 15 446 patients underwent NeuroSAFE. The number of nerve-sparing procedures was higher for patients with NeuroSAFE than for controls in all studies. Cumulative analyses showed a statistically significantly lower risk of positive surgical margins (PSMs) in favor of NeuroSAFE (odds ratio [OR] 0.68, 95% confidence interval [CI] 0.51–0.91, I² = 79%) and no difference in 2-yr biochemical recurrence (BCR; OR 0.79, 95% CI 0.53–1.18, I² = 63%). All studies with control groups showed higher potency rates in the NeuroSAFE group; none reported significant difference in continence rates. Adverse events were scarce. Limitations of the studies include a lack of randomization resulting in a selection bias; the overall risk of bias judgment ranged from low to serious.

Conclusions and clinical implications

We present the first systematic review on NeuroSAFE during RP. The level of evidence is weak. The increased rate of nerve-sparing surgery, reduced PSMs, similar BCR, and low adverse event rates imply that NeuroSAFE is an oncologically safe technique. NeuroSAFE seems to improve functional outcomes, especially potency, but results of randomized trials are awaited.

Patient summary

We know that for patients with prostate cancer who undergo an operation to remove the prostate, sparing the nerve bundles next to each side of the prostate improves continence and erectile function. In this literature review, we evaluated a technique (NeuroSAFE) that aids surgeons in deciding whether they can spare these nerve bundles safely while still operating radically, for example, remove all cancer. We found that the technique is oncologically safe. Furthermore, the impact on potency appears promising but needs further study.