Outcomes of Prostate-specific Antigen-based Prostate Cancer Screening Among Men Using Nonsteroidal Anti-inflammatory Drugs

Background: The Finnish Randomized Study of Screening for Prostate Cancer (FinRSPC), the largest component of the European Randomized Study of Screening for Prostate Cancer (ERSPC), showed a smaller, nonsignificant reduction in prostate cancer-specific mortality by systematic prostate-specific antigen (PSA)-based screening compared with the overall ERSPC results. Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce inflammation and also PSA elevations due to intraprostatic inflammation. Objective: To explore whether NSAID usage modifies the effects of PSA-based screening on prostate cancer incidence and mortality. Design,setting and participants: A cohort of 78 165 men from the FinRSPC were linked to a comprehensive national prescription database to obtain information on NSAID reimbursements prior to screening. Outcome measurement and statistical analysis: Prostate cancer risk and mortality were compared between the FinRSPC screening arm and the control arm among NSAID users and nonusers using an age-adjusted Cox regression model. Results and limitations: Screening increased the detection of Gleason 6 (hazard ratio [HR] 1.59, 95% confidence interval [CI] 1.47-1.72 and HR 1.39, 95% CI 1.26-1.54) and localized prostate tumors (HR 1.25, 95% CI 1.18-1.32 and HR 1.11, 95% CI 1.03-1.20) more among baseline NSAID nonusers than among users, respectively (p for interaction <0.04 for both). This difference was observed in all three screening rounds. Detection of metastatic prostate cancer was similar in both NSAID users and nonusers. Screening decreased prostate cancer mortality among men using NSAIDs at FinRSPC randomization (HR 0.66, 95% CI 0.49-0.90) but not among nonusers (HR 0.95, 95% CI 0.81-1.12); p for interaction = 0.04. Conclusions: Screening detected fewer well-differentiated localized tumors among NSAID users than among nonusers. This suggests that PSA screening may cause less overdiagnosis within this subgroup, whereas mortality benefit may be greater among NSAID users. Patient summary: Prostate cancer screening causes less overdiagnosis of well-differentiated localized prostate tumors among men who use nonsteroidal anti-inflammatory drugs. (C) 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.