5α-reductase inhibitors linked to elevated prostate cancer death rates
medwireNews: Use of 5α-reductase inhibitors (5-ARI), typically for benign prostatic hyperplasia, may delay prostate cancer diagnosis and thus increase mortality risk, show results of a large population-based cohort study.
Brent Rose (University of California, La Jolla, USA) and co-investigators say their findings “highlight a continued need to raise awareness of 5-ARI-induced PSA [prostate-specific antigen] suppression, establish clear guidelines for early prostate cancer detection, and motivate systems-based practices to facilitate optimal care for men who use 5-ARIs.”
The study included 80,875 men within the US Veterans Affairs healthcare system who were diagnosed with stage I–IV prostate cancer between 2001 and 2015. Of these, 8587 (10.6%) were prescribed 5-ARIs a year or more prior to prostate cancer diagnosis, with a median treatment duration before diagnosis of 4.85 years.
The researchers report in JAMA Internal Medicine that, at the time of biopsy, the adjusted PSA value (adjusted by doubling, in line with previous clinical trials) was more than twice as high among the 5-ARI users than among nonusers, at 13.5 ng/mL versus 6.4 ng/mL.
Among men with a known biopsy date, the median time from first adjusted elevated PSA (≥4 ng/mL) to diagnosis was significantly greater for 5-ARI users than nonusers (3.60 vs 1.40 years), with just 29% of 5-ARI users having a biopsy within 2 years of the first elevated PSA result versus 59% of nonusers.
Furthermore, at diagnosis, 5-ARI users were significantly more likely than nonusers to have Gleason grade 8 or higher (25.2 vs 17.0%), clinical stage T3 or higher (4.7 vs 2.9%), node-positive (3.0 vs 1.7), and metastatic (6.7 vs 2.9%) disease.
Rose and team found that the 12-year cumulative prostate cancer-specific mortality rate was significantly higher among 5-ARI users than nonusers, at 13% versus 8%, while multivariate analysis revealed that men who took 5-ARIs had a significant 39% increased risk for death from prostate cancer than those who did not.
5-ARI users also had a 10% increased risk for all-cause mortality relative to nonusers, but there was no difference between the two groups in non-cancer mortality risk.
In sensitivity analyses, the investigators showed that neither decreasing the 5-ARI exposure window to 1.5 months before cancer diagnosis, nor increasing it to 2.0 years, altered the prostate cancer-specific or all-cause mortality findings.
Rose and co-authors conclude: “Our data suggest that PSA suppression in 5-ARI users was not routinely accounted for during prostate cancer screening and led to delays in prostate cancer diagnosis, which in turn may have resulted in advanced disease and worsened clinical outcomes.”
They add: “One reason that clinicians may not routinely address PSA suppression is that published guidelines do not clearly state the optimal method” for doing so.
Rose et al also say that their findings highlight “an opportunity to build systems-based practices to facilitate accurate interpretations of common laboratory tests affected by medication use.”
By Laura Cowen
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