San Diego, CA—Medications for symptoms of benign prostatic hyperplasia (BPH) can help relieve the troublesome symptoms but also might have some downsides, according to a new study.

A report in JAMA Internal Medicine cautioned that patients using drugs that inhibit the enzyme 5-alpha-reductase (5-ARI) were at risk of a 2-year delay in diagnosis of their prostate cancer. Furthermore, according to the University of California San Diego School of Medicine–led researchers, those men also were twice as likely to have advanced disease upon diagnosis.

BPH patients on 5-ARIs were diagnosed with prostate cancer an average of 3.6 years after the first signs of elevated levels of prostate-specific antigen (PSA) versus 1.4 years for men who did not use the drugs.

The information is especially significant because most men above age 50 years have some level of BPH, in which an enlarged prostate can impede on the urethra, according to background information in the article.

“Our study demonstrates how important it is to raise awareness among medical care teams and patients that 5-ARI inhibitors can cause PSA-suppression,” explained senior author Brent S. Rose, MD, assistant professor in the Department of Radiation Medicine and Applied Sciences at UC San Diego School of Medicine. “In addition, there is a need to create clear guidelines for early prostate cancer detection to facilitate optimal care for men prescribed 5-ARIs.”

Past research has indicated that 5-ARI treatment can cause a 50% reduction in the levels of PSA.

Researchers sought to test their hypothesis that prediagnostic 5-ARI use is associated with a delayed diagnosis, more advanced disease at diagnosis, and higher risk of prostate cancer–specific mortality and all-cause mortality than use of other or no PSA-decreasing drugs.

To do that, they conducted a population-based cohort study linking the Veterans Affairs Informatics and Computing Infrastructure with the National Death Index to obtain patient records for 80,875 men with American Joint Committee on Cancer stage I-IV prostate cancer diagnosed from January 1, 2001, to December 31, 2015. Follow-up continued until death or December 31, 2017, with data analysis performed from March 2018 to May 2018.

Overall, median (interquartile range [IQR]) age at diagnosis was age 66 (61-72) years, and median IQR follow-up was 5.90 (3.50-8.80) years, according to the study.

Results indicated, however, that median time from first adjusted elevated PSA to diagnosis was significantly greater for 5-ARI users than 5-ARI nonusers (3.60 [95% CI, 1.79-6.09] years versus 1.40 [95% CI, 0.38-3.27] years; P <.001) among patients with known prostate biopsy date.

In addition, median adjusted PSA at time of biopsy was significantly higher for 5-ARI users than 5-ARI nonusers (13.5 ng/mL vs. 6.4 ng/mL; P <.001). Furthermore, the study team emphasized, patients treated with 5-ARI were more likely to have Gleason grade 8 or higher (25.2% vs. 17.0%; P <.001), clinical stage T3 or higher (4.7% vs. 2.9%; P <.001), node-positive (3.0% vs. 1.7%; P <.001), and metastatic (6.7% vs. 2.9%; P <.001) disease than 5-ARI nonusers.

Researchers pointed out that in a multivariable regression, patients who took 5-ARI had higher prostate cancer–specific (subdistribution hazard ratio [SHR], 1.39; 95% CI, 1.27-1.52; P <.001) and all-cause (HR, 1.10; 95% CI, 1.05-1.15; P <.001) mortality.

“Results of this study demonstrate that pre-diagnostic use of 5-ARIs was associated with delayed diagnosis and worse cancer-specific outcomes in men with prostate cancer,” study authors concluded. “These data highlight a continued need to raise awareness of 5-ARI-induced PSA suppression, establish clear guidelines for early prostate cancer detection, and motivate systems-based practices to facilitate optimal care for men who use 5-ARIs.”

“Using PSA screening continues to be an effective tool for prostate cancer detection among men using 5-ARI, so long as PSA levels are adjusted for PSA suppression that occurs while taking these drugs,” noted first author Reith R. Sarkar, MAS. “Our data suggest that PSA suppression in this population was not routinely accounted for during screening for prostate cancer and that this led to delays in diagnosis, which may have resulted in advanced disease and worsened clinical outcomes.”

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