The impact of multifocal perineural invasion on biochemical recurrence and timing of adjuvant androgen‐deprivation therapy in high‐risk prostate cancer following radical prostatectomy

Perineural invasion (PNI) is a distinct pathologic entity and a recognized source of tumor spread. However, the role of PNI in high-risk prostate cancer (PCa) has not been explored. The aims of the study were to investigate the impact of PNI on biochemical recurrence (BCR) and optimal timing of adjuvant androgen-deprivation therapy (ADT) after radical prostatectomy (RP).A total of 265 prostatectomies, median follow-up 45 months, were assessed for the presence and intensity of PNI (unifocal and multifocal) in RP specimens. Kaplan-Meier curves were used to estimate BCR probabilities. Cox proportional hazard models were used to address predictors of BCR. Harrell's C-index was conducted to further validate prognostic value of multi-PNI.A total of 123 patients (46.4%) were PNI positive, among which, 91 (74%) and 32 (26%) had unifocal PNI (uni-PNI) and multifocal PNI (multi-PNI), respectively. The presence of multi-PNI was strongly associated with increasing incidence of BCR (HR = 3.87, 95%CI: 1.66-9.01, P = 0.002). Patients with uni-PNI had a similar BCR rate to those without PNI after adjuvant ADT. For men with multi-PNI, immediate ADT was superior to delayed ADT in decreasing biochemical failure.Our findings suggest that detection of multi-PNI in high-risk RP specimens could be a prognosticator for early biochemical relapse post-surgery. Initiation of adjuvant therapy may be appropriate in patients with multi-PNI as soon as possible after surgery.