Presentation Authors: Reith Sarkar, J Parsons*, Alex Bryant, Stephen Ryan, John Einck, A Karim Kader, Rana McKay, Arno Mundt, Christopher Kane, James Murphy, Brent Rose, La Jolla, CA
Introduction: 5Î±-Reductase inhibitors (5-ARIs), commonly used to treat benign prostatic hyperplasia, reduce serum prostate-specific antigen (PSA) concentrations by 50%. The effect of 5-ARIs on prostate cancer detection in a PSA-screened population remains unclear. We tested the hypothesis that pre-diagnostic 5-ARI use is associated with a delayed diagnosis, more advanced disease, and higher risk of prostate cancer-specific mortality and all-cause mortality.
Methods: We linked the Veterans Affairs Informatics and Computing Infrastructure with the National Death Index to obtain patient records. The cohort included 80,875 men with American Joint Committee on Cancer stage I-IV prostate cancer diagnosed from 2001-2015. The exposure was pre-diagnostic 5-ARI use. The main outcomes were time from initial PSA elevation (defined as PSA â‰¥ 4 ng/mL) to diagnostic prostate biopsy, cancer grade and stage at time of diagnosis, and prostate cancer-specific and all-cause mortality. PSA was adjusted by doubling the value for 5-ARI users, consistent with prior clinical trials.
Results: Median follow-up was 5.9 years. Median time from first adjusted elevated PSA to diagnosis was significantly greater for 5-ARI users than 5-ARI non-users (3.60 years vs. 1.40 years; p < 0.001). Median adjusted PSA at time of biopsy was significantly higher for 5-ARI users than 5-ARI non-users (13.5 ng/mL vs. 6.5 ng/mL; p < 0.001). 5-ARI patients were more likely to have Gleason â‰¥ 8 (25% vs. 17%; p < 0.001), clinical stage â‰¥ T3 (5% vs. 3%; p < 0.001), node positive (3% vs. 2%; p < 0.001), and metastatic (7% vs. 3% p < 0.001) disease than 5-ARI non-users. In a multivariable regression, 5-ARI patients had higher prostate cancer-specific (SHR 1.39; 95% CI 1.27-1.52; p < 0.001) and all-cause (HR 1.10; 95% CI 1.05-1.15; p < 0.001) mortality.
Conclusions: Pre-diagnostic use of 5-ARIs was associated with delayed diagnosis and worse cancer-specific outcomes in men with prostate cancer. These data highlight an important need to raise awareness of 5-ARI-induced PSA suppression, establish clear guidelines for early prostate cancer detection, and motivate systems-based practices to facilitate optimal care for men who use 5-ARIs.