5-ARIs for Benign Prostatic Hyperplasia Can Lead to Delayed Prostate Cancer Diagnosis

The use of 5α-reductase inhibitors (5-ARIs) to treat benign prostatic hyperplasia (BPH) was associated with a delay in the diagnosis of prostate cancer, according to a new study. Men also had poorer cancer-specific outcomes, highlighting a need for awareness of prostate-specific antigen (PSA) suppression with these agents.

5-ARIs including finasteride and dutasteride can reduce prostate volume and relieve urinary outflow obstruction, and they also depress serum PSA concentrations by approximately 50%. “Randomized trials have shown that PSA screening remains effective for prostate cancer detection among men taking 5-ARIs if the observed PSA level is adjusted to obtain the true PSA level,” wrote study authors led by Reith R. Sarkar, MAS, of the University of California, San Diego. “However, anecdotal evidence has led to speculation that 5-ARI–induced PSA suppression is not routinely addressed in the general medical community.”

The researchers tested whether prediagnostic 5-ARI use would be associated with delayed diagnosis and more advanced disease at diagnosis in a population-based cohort study using the Veterans Affairs Informatics and Computing Infrastructure linked to the National Death Index. They included a total of 80,875 men diagnosed with prostate cancer between 2001 and 2015, followed until death or until the end of 2017; the results were published in JAMA Internal Medicine.

A total of 8,587 men (10.6%) were prescribed 5-ARIs for a minimum of 1 year prior to a prostate cancer diagnosis; most of these (8,406 patients) received finasteride. The median 5-ARI treatment duration before the diagnosis was 4.85 years.

The researchers found that 5-ARI users had a significantly higher prostate cancer–specific mortality, which was the study’s primary endpoint, with a hazard ratio (HR) of 1.39 (95% CI, 1.27–1.52; P < .001). They also had a higher all-cause mortality, with an HR of 1.10 (95% CI, 1.05–1.15; P < .001).

Patients treated with 5-ARIs also had a greater median time from first elevated PSA to diagnosis, at 3.60 years compared with 1.40 years (P < .001). The median adjusted PSA at the time of prostate biopsy was 13.5 ng/mL for 5-ARI users, compared with 6.4 ng/mL in non-users (P < .001).

Users of 5-ARIs also had worse cancer characteristics at the time of diagnosis. They were more likely to have Gleason grade 8 disease or higher (25.2% vs 17.0%; P < .001), as well as clinical stage T3 or higher, node-positive disease, and metastatic disease.

“These data suggest that adjustment for 5-ARI–induced PSA suppression was not routinely incorporated in this population,” the authors concluded. “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 for 5-ARI users.”

E. David Crawford, MD, of the University of Colorado Anschutz Medical Campus, who was not involved with the research, said many “black clouds” have hung over the use of 5-ARIs, including a potential risk for inducing high-grade cancers. He said that once a man is on a 5-ARI for 4 to 8 months, the new PSA level could be considered the new baseline. “If the level elevates, then this is a red flag to trigger evaluation,” Crawford said. “The authors are correct in stating that we need to establish very clear guidelines for cancer detection, which was absent in the VA cohort.”