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

Abstract

Background: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. Objectives: We aim to investigate the clinical significance of PNI in patients with mPCa. Materials and methods: 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. Results: 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). Discussion and Conclusion: 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.

Impact of positive surgical margin location and perineural invasion on biochemical recurrence in patients undergoing radical prostatectomy

“…Our results showed that 30.5% of patients had PNI, while the incidence in other research ranged from 21.1 to 50.2% [ 13 , 27 – 30 ]. The variation between these studies may be associated with different patient groups or pathological criteria.…”

Schwann Cell-Derived CCL2 Promotes the Perineural Invasion of Cervical Cancer

“…Neoplastic cells infiltrating into the perineurium space were spared by tumor resection, leading to local recurrence (31). PNI has been reported as an important danger factor for independent survival, indicating poor prognosis for many malignancies, including prostate cancer (32)(33)(34), colon cancer (35)(36)(37), head and neck cancer (38), gastric cancer (39), and cervical cancer (40). In cervical cancer, PNI could be considered as an indication guiding the operation and postoperative adjuvant therapy (41).…”

Quantification of perineural invasion focus after radical prostatectomy could improve predictive power of recurrence

“…Furthermore, Ciftci et al (43) reported that biopsy PNI was associated with increased bone metastasis in PCa. In addition, Zhao et al (44) found that multifocal PNI in biopsy specimen was an independent adverse prognosticator for both castration-resistant PCafree survival and OS in patients with favorable/intermediate-risk metastatic PCa patients when compared to PNI-patients. However, due to the present under-reporting of PNI in clinical practice which hampered the precise evaluation of its true clinical significance, it was reported that only 43% of all the urologists would consider biopsy PNI in pathology reports to have an influence on their decisions when selecting treatment options for PCa patients.…”