The clinical significance of perineural invasion in patients with de novo metastatic prostate cancer.

Abstract

The clinical value of perineural invasion (PNI) in patients with localized prostate cancer (PCa) is widely explored. However, its role in metastatic PCa (mPCa) remains unknown. We aim to investigate the clinical significance of PNI in patients with mPCa. Data of 515 mPCa patients between 2012 and 2018 were retrospectively studied. PNI and its intensity were identified by prostate biopsy. The prognostic value of PNI was evaluated by Kaplan-Meier curves and Cox proportional-hazards model. Perineural invasion was detected in 170/515 (33.0%) cases. Among them 73/170 (42.9%) and 97/170 (57.1%) harbored unifocal PNI (uni-PNI) and multifocal PNI (multi-PNI), respectively. Compared to patients without PNI, those with PNI had statistically shorter castration-resistant PCa-free survival (CFS) and numerically shorter overall survival (OS) (mCFS: 15.4- vs. 18.5-Mo, p=0.015; mOS: 63.8- vs. 71.4-Mo, p=0.108). Patients harboring multi-PNI were associated with poorer clinical outcomes than those with uni-PNI (mCFS: 12.4- vs. 18.0-Mo, p=0.040; mOS: 39.7-Mo vs. NR, p=0.018) or those without PNI (mCFS: 12.4- vs. 18.5-Mo, p=0.002; mOS: 39.7- vs. 71.4-Mo, p=0.002). Totally, neither uni-PNI nor multi-PNI was an independent risk factor impacting survival outcomes in multivariate analyses. While remarkably, for patients with favorable/intermediate-risk mPCa, multi-PNI was an independent adverse prognosticator for both CFS and OS (CFS: HR: 1.705, 95% CI: 1.029-2.825, p=0.038; OS: HR: 3.294, 95% CI: 1.464-7.413, p=0.004). This study filled the blank of the clinical significance of PNI in mPCa. We found that multi-PNI could distinguish men with relatively poor prognosis from patients initially regarded as with favorable survival outcomes by other prognosticators, and thus, avoid disease underestimation in this group of patients. Our finding would help physicians have a deeper understanding of the heterogeneity of mPCa and make better individualized therapeutic strategy.