The Perineural Invasion Paradox: Is Perineural Invasion an Independent Prognostic Indicator of Biochemical Recurrence Risk in Patients With pT2N0R0 Prostate Cancer? A Multi-Institutional Study

PURPOSE: Perineural invasion (PNI) is a histologic feature that is present in as many as 84% of patients with prostate cancer. The prognostic significance of PNI is controversial, with recent studies yielding contradictory results. This study aims to assess whether PNI, on the surgical pathology of patients with pT2N0M0 disease and with negative surgical margins, is an independent prognostic indicator of the risk of biochemical recurrence. METHODS AND MATERIALS: We identified 1549 patients who received a diagnosis of margin-negative pT2N0M0 prostate cancer at 3 separate institutions between January 1, 2008 and December 31, 2014. We reviewed the electronic medical records of these patients and collected clinical and histologic data. A multivariable analysis was performed to assess the association between PNI and biochemical recurrence. RESULTS: Of the 1549 patients identified, 936 (60.4%) had PNI and 96 (6.2%) had biochemical recurrence. The median time until recurrence was 16 months. The median follow-up in patients without recurrence was 26.5 months. PNI was associated with pT2c disease. The proportion of patients with pT2c was 89% in patients with PNI compared with 79% in patients without PNI (P < .001). PNI was also associated with a higher surgical Gleason score (of those with vs without PNI, 21% vs 50% had Gleason score 3 + 3; 62% vs 41% had a Gleason score 3 + 4, 12% vs 5% had a Gleason score 4 + 3; and 5% vs 3% had a Gleason score 8-10; P < .001). On univariate analysis, patients with PNI appeared to be more likely to have disease recurrence (hazard ratio: 1.7; 95% confidence interval, 1.1-2.6; P = .015). However, after adjusting for other variables, there was not a significant association between PNI and recurrence (hazard ratio: 1.1; 95% confidence interval, 0.70-1.8: P = .65). CONCLUSIONS: We found that PNI was not an independent indicator of the risk of biochemical recurrence. Instead, PNI may be an indicator of unfavorable histology such as a high Gleason score or diffuse disease within the prostate in pT2N0 patients.