Worse Prostate Cancer Outcomes With 5-Alpha-Reductase Inhibitors

By Will Boggs MD

May 10, 2019

NEW YORK (Reuters Health) - Treatment with 5-alpha-reductase inhibitors (5-ARIs) is associated with shorter time to diagnosis and worse mortality in prostate cancer, according to findings from Veterans Affairs electronic health records.

"5-ARIs like finasteride and dutasteride reduce the PSA by about 50%," Dr. Brent S. Rose, from the University of California, San Diego in La Jolla, told Reuters Health. "It is very important to adjust the PSA for men on 5-ARIs to avoid the possibility of delayed prostate cancer detection."

5-ARIs, commonly used to treat benign prostatic hyperplasia (BPH), reduce prostate volume and relieve urinary outflow obstruction. These medications depress serum PSA concentrations, but there are no data on the association of 5-ARI use with prostate cancer detection and outcomes among men who participate in prostate cancer screening.

Dr. Rose and colleagues used data from the Veterans Affairs Informatics and Computing Infrastructure to test their hypothesis that 5-ARI-induced PSA suppression may lead to delays in prostate cancer diagnosis, higher grade and stage at diagnosis, and higher risk of prostate cancer-specific mortality.

The study included 80,875 men who participated in prostate cancer screening, 8,587 (10.6%) of whom were prescribed 5-ARIs at least one year before prostate cancer diagnosis (median treatment duration before diagnosis, 4.85 years).

The median delay from first elevated (adjusted) PSA to prostate biopsy was significantly longer among 5-ARI users (3.60 years) than among those taking alpha-blockers (2.11 years) or those taking neither alpha-blockers nor 5-ARIs (1.17 years), according to the May 6th JAMA Internal Medicine online report.

The unadjusted PSA was similar (but statistically different) between 5-ARI users (6.8 ng/mL), alpha-blocker users (6.4 ng/mL), and users of neither (6.4 ng/mL), whereas the adjusted PSA was approximately twice as high in the 5-ARI group (13.5 ng/mL) as in the other groups (6.4 ng/mL for both).

5-ARI users had their prostate biopsy later than 5-ARI nonusers across all age groups after first elevated PSA.

5-ARI users were significantly more likely than nonusers to present with disease that was higher grade (Gleason score, 8-10), clinically T3 or 4, clinically node positive, and clinically metastatic.

The 12-year cumulative incidence of prostate cancer-specific mortality and all-cause mortality were significantly higher among men who received 5-ARIs (13% and 45%, respectively) than among men who received alpha-blockers (8% and 42%, respectively) or those who received neither medication (8% and 36%, respectively).

Increasing the dose intensity of 5-ARI use increased the risk of prostate cancer-specific mortality.

"While PSA screening is somewhat controversial, physicians and patients who choose to pursue PSA screening need to understanding the effects of 5-ARIs on PSA suppression in order to avoid delayed diagnosis and potentially worse outcomes," Dr. Rose said.

SOURCE: http://bit.ly/2E09JkC

JAMA Intern Med 2019.