Both acute and chronic inflammation are associated with lower perineural invasion in men with prostate cancer on repeat biopsy

Objectives: To evaluate the association between acute and chronic inflammation with the presence of perineural invasion (PNI) in prostate biopsies positive for prostate cancer (PCa). Material and methods: Retrospective analysis of 1399 prostate biopsies positive for PCa in the Reduction by Dutasteride of PCa Events (REDUCE) study. PCa, acute and chronic prostate inflammation, and PNI were assessed by central pathology review. The association between acute and chronic inflammations with PNI was evaluated using chi-square test and Kruskal-Wallis tests, and logistic regression adjusting for clinicopathological and biochemical variables. Results: PNI was identified in 133 (9.5%) biopsies. 267 (19.1%) biopsies had acute inflammation, 1038 (74.2%) had chronic inflammation, and 255 (18.2%) had both. The presence of acute and chronic inflammations was associated with each other (P<0.001). Chronic inflammation was associated with lower Gleason score (P=0.009) and lower tumor volume (P<0.001), while acute inflammation was associated with lower Gleason score (P=0.04), lower tumor volume (P=0.004) and higher prostate-specific antigen levels (P=0.05). In both uni- and multivariable analyses, chronic prostate inflammation was significantly associated with less PNI (univariable OR=0.54; 95% CI=0.37-0.79; P=0.001; multivariable OR=0.65; 95% CI=0.43-0.99; P=0.045). Acute prostate inflammation was associated with less PNI only in univariable analysis (univariable OR=0.51; 95% CI=0.29-0.89, P=0.018; multivariable OR=0.63; 95% CI=0.35-1.13; P=0.12). Conclusion: Acute and chronic prostate inflammation were both associated with a lower prevalence of PNI in prostate biopsies positive for PCa. If confirmed, this suggests that inflammation and immunomodulation can serve as areas of potential therapeutic design to mitigate PNI in PCa patients.