5-Alpha reductase inhibitor use and prostate cancer survival in the Finnish Prostate Cancer Screening Trial

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Abstract

Randomized clinical trials have shown that use of 5α-reductase inhibitors (5-ARIs) lowers overall prostate cancer (PCa) risk compared to placebo, while the proportion of Gleason 8–10 tumors is elevated. It is unknown whether this affects PCa-specific survival. We studied disease-specific survival by 5-ARI usage in a cohort of 6,537 prostate cancer cases diagnosed in the Finnish Prostate Cancer Screening Trial and linked to the national prescription database for information on medication use. Cox proportional hazards regression was used to estimate hazard ratios and 95% confidence intervals for prostate cancer-specific deaths. For comparison, survival among alpha-blocker users was also evaluated. During the median follow-up of 7.5 years after diagnosis a total of 2,478 men died; 617 due to prostate cancer and 1,861 due to other causes. The risk of prostate cancer death did not differ between 5-ARI users and nonusers (multivariable adjusted HR 0.94, 95% CI 0.72–1.24 and HR 0.98, 95% CI 0.69–1.41 for usage before and after the diagnosis, respectively). Alpha-blocker usage both before and after diagnosis was associated with increased risk of prostate cancer death (HR 1.29, 95% CI 1.08–1.54 and HR 1.56, 95% CI 1.30–1.86, respectively). The risk increase vanished in long-term alpha-blocker usage. Use of 5-ARIs does not appear to affect prostate cancer mortality when used in management of benign prostatic hyperplasia. Increased risk associated with alpha-blocker usage should prompt further exploration on the prognostic role of lower urinary tract symptoms.

What's new

Inhibitors of 5alpha-reductase enzyme (5-ARIs) are commonly used in the treatment of benign prostatic hyperplasia (BPH). But while clinical trials showed that 5-ARIs lower overall prostate cancer (PCa) risk compared to placebo, they reported a higher proportion of high-grade tumors among long-term users. Here, the authors evaluated PCa-specific survival for 5-ARIs users and non-users among men diagnosed with prostate cancer. The previously reported elevated risk of high-grade PCa among 5-ARIs users does not affect the risk of PCa death, at least in the short-term. Alpha-blockers, also commonly used in BPH management, appear indicative of an impaired prognosis in PCa patients.

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