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

Background: 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). Methods: 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. Results: 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. Conclusions: 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.