Is nerve-sparing radical prostatectomy oncological appropriate for all ISUP 2 cancers?

BACKGROUND: The aim of this study is to evaluate the impact of perineural invasion (Pn1) as an independent predictor of biochemical recurrence (BCR) in patients undergoing nerve-sparing radical prostatectomy (NSRP) for ISUP 2 prostate cancer (PCa).METHODS: A retrospective analysis was conducted comprising 435 patients with ISUP 2 PCa treated with NSRP at our department between 2010 and 2020. All patients had a pure adenocarcinoma and a preoperative levels of PSA<10 ng/mL. Clinical parameters, mpMRI findings and pathological outcomes were assessed using univariate and multivariate logistic regression models to determine predictors of Pn1 and BCR after radical prostatectomy (RP).RESULTS: Out of 435 patients, 330 (76%) had Pn1 histology in the RP specimens. Type II Diabetes Mellitus (P=0.038), smaller prostate volume (P=0.012), and high PI-RADS scores (P=0.037) were identified as independent predictors of Pn1. Patients with Pn1 showed a significantly higher incidence of R1 resection margins (22% vs. 10%; P=0.005) and BCR (43 vs. 12 cases; P=0.004) after a median time of 29.4 months (mean 40±37.2 months). In addition, the lesion in the peripheral medial and right transition zones showed a significant correlation with Pn1 (P=0.016 and P=0.044 respectively). Conversely, the lesion in the left lateral base was found to be protective to perineural invasion risk (coefficient of -0.996, P=0.032).CONCLUSIONS: Pn1 is a prevalent finding in patients with ISUP 2 PCa undergoing NSRP and is linked to worse oncological outcomes. Preoperative T2DM, smaller prostate volume, and high PI-RADS lesions (PI-RADS 4 or 5) should be carefully evaluated to optimize patient selection and surgical planning.