Perineural Invasion in Radical Prostatectomy Specimens and Its Association with Biochemical Recurrence and Survival in Prostate Cancer: A Systematic Review and Meta-analysis.

[BACKGROUND AND OBJECTIVE] Perineural invasion (PNI) in prostate cancer (PC) has been linked to adverse oncological outcomes. The objective of this study was to evaluate the association between PNI identified in radical prostatectomy (RP) specimens and survival outcomes.

[METHODS] A systematic literature search was conducted in December 2024 using PubMed (MEDLINE), Embase, Scopus, and Web of Science Core Collection databases. We included studies reporting on PNI in RP specimens and its association with primary endpoints (biochemical recurrence [BCR] or BCR-free survival) and/or secondary endpoints (cancer-specific survival [CSS], overall survival, recurrence-free survival, disease-free survival [DFS], or metastasis-free survival).

[KEY FINDINGS AND LIMITATIONS] A total of 58 studies met the inclusion criteria. A meta-analysis of 40 studies (27 030 patients) demonstrated that PNI was associated with BCR (pooled hazard ratio [HR] 1.40, 95% confidence interval [CI] 1.28-1.52;  < 0.001). Further analyses showed that PNI was linked to worse CSS ( = 903; pooled HR 2.9, 95% CI 1.1-8.1;  = 0.048). The association with DFS was not statistically significant ( = 1008; pooled HR 1.8, 95% CI 0.7-4.3;  = 0.1). The main limitation is the reliance on predominantly retrospective studies with small samples and high risk of bias.

[CONCLUSIONS] Our findings indicate that PNI identified in RP specimens is associated with higher risk of BCR, as well as worse CSS, which underscores its relevance as a prognostic factor in PC.

[PATIENT SUMMARY] We found that detection of cancer cells around nerves, which is called perineural invasion (PNI), in specimens after surgery to remove the prostate, is linked to a higher chance of worse survival outcomes in prostate cancer. Men with PNI were more likely to experience biochemical recurrence and had worse cancer-specific survival. PNI may help in identifying patients at higher risk after surgery who could benefit from closer follow-up or additional treatment. However, more high-quality studies are needed to confirm its role in guiding long-term care.