Prognostic significance of perineural invasion and lymphovascular invasion following robot-assisted radical prostatectomy with negative surgical margins: a retrospective study from a high-volume center.

Purpose: Perineural invasion (PNI) and lymphovascular invasion (LVI) represent tumor escape mechanisms at radical prostatectomy (RP). We assessed their prognostic significance for biochemical recurrence (BCR) following complete resection.

Methods: We analyzed 10,471 men with negative surgical margins after RP, stratified into three groups based on pathological PNI and LVI status: Group 1 (PNI-/LVI-, n = 1,925), Group 2 (PNI+/LVI-, n = 7,849), and Group 3 (LVI+, n = 697; 14 with PNI-/LVI + and 683 with PNI+/LVI+). The cumulative probability of BCR (PSA > 0.2 ng/mL after initial undetectable level), cancer-specific mortality, and all-cause mortality were compared using Kaplan-Meier curves and log-rank tests. Multivariable Cox regression adjusted for age, race, comorbidity, PSA at biopsy, final grade group, pathological T and N stage, and tumor diameter.

Results: The median follow-up was 60 months (IQR: 18-108). Pathological N1 disease was more frequent in Group 3 (5.7%) than in Group 1 (0.1%) and Group 2 (0.3%). Compared with Group 1, the unadjusted hazard ratios (HRs) for BCR were 6.07 (95% CI: 4.30-8.56) in Group 2 and 23.4 (95% CI: 16.3-33.6) in Group 3; adjusted HRs were 2.51 (95% CI: 1.76-3.58) and 3.79 (95% CI: 2.55-5.53), respectively. Mortality outcomes were comparable across groups, both before and after the adjustment.

Conclusion: Our study demonstrated that the combination of PNI and LVI independently predicted BCR following complete resection. Their integration into postoperative risk assessment may improve BCR prediction and guide individualized follow-up planning. Longer follow-up is required to draw definitive conclusions regarding their impact on mortality outcomes.