A recent phase 3 trial published in The Lancet Oncology has demonstrated that the NeuroSAFE technique significantly improves postoperative erectile function and short-term urinary continence in patients undergoing robot-assisted radical prostatectomy (RARP) for localised prostate cancer.
Study Overview
The NeuroSAFE PROOF trial was a multicentre, patient-blinded, randomised controlled study that enrolled 407 patients between January 6, 2019, and December 6, 2022. Of these, 381 underwent surgery—190 in the NeuroSAFE group and 191 in the standard RARP group. The primary endpoint was erectile function at 12 months, assessed using the International Index of Erectile Function-5 (IIEF-5) score. Secondary endpoints included urinary continence scores at 3 and 6 months, evaluated using the International Consultation on Incontinence Questionnaire (ICIQ), and the erectile function domain of the IIEF (IIEF-6) scores at 12 months.
Key Findings
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Erectile Function: At 12 months, the mean IIEF-5 score was 12.7 (SD 8.0) in the NeuroSAFE group compared to 9.7 (SD 7.5) in the standard RARP group, yielding an adjusted mean difference of 3.18 (95% CI 1.62 to 4.75; p<0.0001).
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Urinary Continence: At 3 months, the ICIQ score was significantly lower in the NeuroSAFE group than in the standard RARP group (adjusted mean difference –1.41 [95% CI –2.42 to –0.41]; p=0.006), indicating better urinary continence. By 6 months, no significant difference was observed between the groups (adjusted mean difference –0.37 [95% CI –1.35 to 0.62]; p=0.46).
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Oncological Outcomes: At 12 months, prostate-specific antigen (PSA) persistence or biochemical recurrence occurred in 9% of participants in the NeuroSAFE group versus 6% in the standard RARP group.
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Adverse Events: Serious adverse events occurred in 3% of patients in both groups, with no deaths attributed to the study intervention.
Clinical Implications
The NeuroSAFE technique involves intraoperative frozen-section examination of the prostate’s neurovascular margins to guide nerve-sparing decisions during RARP. This approach allows for more precise preservation of the neurovascular bundles, which is crucial for postoperative functional outcomes.
The trial’s findings suggest that incorporating NeuroSAFE into RARP can lead to significant improvements in erectile function and early urinary continence without compromising oncological safety. Notably, the benefits were more pronounced in patients who were not initially considered candidates for bilateral nerve-sparing, indicating that NeuroSAFE may expand the pool of patients who can safely undergo nerve-sparing procedures.
Conclusion
The NeuroSAFE PROOF trial provides robust evidence supporting the use of the NeuroSAFE technique during RARP to enhance postoperative functional outcomes. These findings advocate for the integration of NeuroSAFE into standard surgical practice for localised prostate cancer, potentially improving quality of life for many patients.
Paper: Dinneen, E., et al. Effect of NeuroSAFE-guided RARP versus standard RARP on erectile function and urinary continence in patients with localised prostate cancer (NeuroSAFE PROOF): a multicentre, patient-blinded, randomised, controlled phase 3 trial. The Lancet Oncology, March 24, 2025. Access online here.