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5-alpha-reductase inhibitors delay prostate cancer diagnosis, worsen outcomes

A recent study found prior use of 5-alpha-reductase inhibitors for benign prostatic hyperplasia was associated with delayed prostate cancer diagnosis and worse prostate cancer outcomes.

“Randomized trials have shown that PSA screening remain effective for prostate cancer detection among men taking [5-alpha-reductase inhibitors (5-ARIs)] if the observed PSA level is adjusted to obtain the true PSA level,” Reith R. Sarkar, MAS, of the department of radiation medicine and applied sciences at the University of California, San Diego, and colleagues wrote. “However, anecdotal evidence has led to speculation that 5-ARI-induced PSA suppression is not routinely addressed in the general medical community.”

Researchers conducted a population-based cohort study using data from the Veteran Affairs Informatics and Computing Infrastructure (VINCI), an electronic health record within the Veterans Affairs health care system that incorporates tumor registry data from individual VA centers. The primary outcome was prostate cancer mortality. Participants were followed up until Dec 31, 2017 or death. Researchers conducted data analysis from March to May 2018.

The study included 80,875 men diagnosed with stage I to IV prostate cancer from Jan. 1, 2001, to Dec. 31, 2015. The median age of the patients was 66 years at the time of diagnosis, and median follow-up was 5.9 years. Among participants, there were 19,065 all-cause deaths, 4,513 of which were attributed to prostate cancer.

Among the patients, 10.6% (n = 8,587) had been prescribed 5-ARIs at least a year prior to prostate cancer diagnosis, with a mean treatment time duration of 4.85 years prior to diagnosis. In patients with a known biopsy date, those who used 5-ARI had a significantly longer time between their first adjusted PSA to prostate cancer diagnosis than those who did not use 5-ARIs (3.6 [95% CI, 1.79-6.09] years vs 1.4 [95% CI, 0.38-3.27] years).

Patients who had been treated with 5-ARIs were more likely to have a clinical stage of T3 or higher (4.7% vs. 2.9%; P < .001) and have node-positive (3.% vs. 1.7%; P < .001) and metastatic (6.7% vs. 2.9%; P < .001) disease than patients who did not use 5-ARIs. A multivariable regression shows that patients who took 5-ARIs prior to prostate cancer diagnosis had a higher rate of all-cause (HR = 1.1; 95% CI, 1.05-1.15) and prostate cancer-specific (subdistribution HR = 1.39; 95% CI, 1.27-1.52) mortality.

“Although these results are hypothesis generating, they highlight a continued need to raise awareness of 5-ARI–induced PSA suppression, establish clear guidelines for prostate cancer detection, and motivate systems-based practices to facilitate optimal care for5-ARI users,” Sarkar and colleagues wrote. – by Erin Michael

Disclosures: The study was supported by a National Institutes of Health grant. Please see study for all other authors’ relevant financial disclosures.