A Prospective Study of Chronic Inflammation in Benign Prostate Tissue and Risk of Prostate Cancer: Linked PCPT and SELECT Cohorts

Abstract

Background: We leveraged two trials to test the hypothesis of an inflammation-prostate cancer link prospectively in men without indication for biopsy.Methods: Prostate Cancer Prevention Trial (PCPT) participants who had an end-of-study biopsy performed per protocol that was negative for cancer and who subsequently enrolled in the Selenium and Vitamin E Cancer Prevention Trial (SELECT) were eligible. We selected all 100 cases and sampled 200 frequency-matched controls and used PCPT end-of-study biopsies as "baseline." Five men with PSA > 4 ng/mL at end-of-study biopsy were excluded. Tissue was located for 92 cases and 193 controls. We visually assessed inflammation in benign tissue. We estimated ORs and 95% confidence intervals (CI) using logistic regression adjusting for age and race.Results: Mean time between biopsy and diagnosis was 5.9 years. In men previously in the PCPT placebo arm, 78.1% of cases (N = 41) and 68.2% of controls (N = 85) had at least one baseline biopsy core (∼5 evaluated per man) with inflammation. The odds of prostate cancer (N = 41 cases) appeared to increase with increasing mean percentage of tissue area with inflammation, a trend that was statistically significant for Gleason sum <4+3 disease (N = 31 cases; vs. 0%, >0-<1.8% OR = 1.70, 1.8-<5.0% OR = 2.39, ≥5% OR = 3.31, P_trend = 0.047). In men previously in the finasteride arm, prevalence of inflammation did not differ between cases (76.5%; N = 51) and controls (75.0%; N = 108).Conclusions: Benign tissue inflammation was positively associated with prostate cancer.Impact: This first prospective study of men without biopsy indication supports the hypothesis that inflammation influences prostate cancer development. Cancer Epidemiol Biomarkers Prev; 26(10); 1549-57. ©2017 AACR.

Figure 1. Inclusion and exclusion of participants from the PCPT and SELECT trials to form the PCPT-SELECT linked cohort

Figure 1 depicts the schema for this study. Cases and controls nested in the PCPT-SELECT linked cohort participated for 7 years in PCPT and spent 1 to 3 years before enrollment in SELECT. Men eligible to be selected as controls participated for 5.5 years in SELECT. Cases diagnosed during SELECT participated for up to 5.5 years. The PCPT end-of-study biopsies served as the baseline biopsies for the PCPT-SELECT linked cohort. Cases were diagnosed a mean of 5.9 years after the PCPT end-of-study biopsy. *A total of 5 men who were eligible for and enrolled in SELECT (had PSA ≤4 ng/mL and normal DRE) were considered to not have an indication for biopsy at the time of the PCPT end of study biopsy even though they had a PSA >4 ng/mL. This resulted from the following PCPT study policy: if during the trial a man had an elevated PSA, was biopsied, and cancer was not found, then a subsequent PSA had to have an increase of ≥50% the prior level or be >10 ng/mL to be considered as an indication for biopsy, including at the end of the trial.