Investigating Association of PNI on Prostate Biopsy with Gleason Score Upgrading at Prostatectomy: a Multi-Institutional Study

Abstract

Perineural invasion (PNI) is a histologic finding observed in up to 84% of patients with prostate cancer (PC), but with conflicting data regarding its prognostic significance. A recent, large, multi-institutional study of PC patients with pT2N0R0 disease found that PNI on histology was not an independent prognostic indicator of biochemical recurrence, but that PNI was associated with higher Gleason score and more diffuse disease within the prostate. We aim to assess whether PNI noted on prostate biopsy in apparently favorable-risk patients is associated with an increased risk of Gleason score upgrading at prostatectomy in patients found to have stage pT2N0M0 disease. We hypothesized that the presence of PNI on prostate biopsy would be associated with an increased risk of surgical Gleason score upgrading in this population. We identified 2,892 patients status post prostatectomy with pT2N0M0 PC from three different institutions diagnosed between 1/1/2008 and 12/31/2014. The electronic medical record was used to obtain age, biopsy and surgical PNI status, biopsy and surgical Gleason score, pre-operative PSA, surgical margin status, clinical and pathological staging, ethnicity, and year of diagnosis for each patient. Multivariable logistic regression (MVA) was used to evaluate for an association between PNI on prostate biopsy and Gleason score upgrading at surgery. Of the 2,892 patients studied, 14.5% (419/2,892) had PNI on biopsy. Of patients with PNI on biopsy, 21.5% (90/419) had Gleason score upgrading at resection, while 28.2% (699/2,473) of patients without PNI on biopsy had Gleason score upgrading at resection (p= 0.0047). On MVA, the odds ratio (OR) of Gleason upgrading at resection for patients with PNI on biopsy relative to patients without PNI on biopsy was 0.69 (p= 0.003, 95% confidence interval (CI) 0.53-0.87). The variables that were statistically significantly associated with Gleason upgrading at resection on MVA were age less than or equal to 60 years (p= 0.018, OR= 1.22, 95% CI 1.03-1.44), and pre-operative PSA greater than 4 ng/mL (p=0.015, OR 1.26, 95% CI 1.05-1.53). In post-prostatectomy patients with favorable-risk PC presence of PNI on initial prostate biopsy was not associated with Gleason score upgrading on resection. This may be due to the association of PNI with more diffuse disease, leading to increased tumor yield on biopsy, and thus more accurate overall grading on biopsy. These findings suggest that for patients with favorable-risk, clinically localized PC, biopsy PNI alone should not be a concern for more aggressive disease requiring pathologic confirmation or intervention. This may help guide treatment decision-making for men debating active surveillance, radiation, and surgery.