Men who take 5-alpha reductase inhibitors (5-ARI) for benign prostatic hyperplasia (BPH) experience delayed prostate cancer (PCa) diagnosis, more advanced disease at diagnosis, and higher mortality risk than men not using these or other PSA-lowering drugs, according to investigators.

Of 80,875 PCa patients within the Veterans Affairs health care system during 2001 to 2015, 10.6% were prescribed 5-ARIs at least 1 year before a PCa diagnosis, including 8406 receiving finasteride and 181 receiving dutasteride. They had a median age at PCa diagnosis of 66 years.

Male veterans treated with 5-ARIs were diagnosed with PCa 2 years later than their counterparts not taking PSA-lowering drugs, Brent S. Rose, MD, of the University of California San Diego (UCSD), and colleagues reported in JAMA Internal Medicine. The median time from first adjusted elevated PSA to diagnosis was 3.6 vs 1.4 years. At time of biopsy, median adjusted PSA was significantly higher in 5-ARI users: 13.5 ng/mL vs 6.4 ng/mL.

Men taking 5-ARIs also had more advanced disease at diagnosis. They were significantly more likely to have Gleason grade 8 or higher (25.2% vs 17.0%), clinical stage T3 or higher (4.7% vs 2.9%), and node-positive (3.0% vs 1.7%), and metastatic (6.7% vs 2.9%) disease than men not taking 5-ARIs.

Of most concern, 5-ARI users had a significant 39% and 10% increased risk of PCa and overall mortality, on multivariable analysis.

“Our study demonstrates how important it is to raise awareness among medical care teams and patients that 5-ARI inhibitors can cause PSA-suppression,” Dr Rose stated in a UCSD news release. “In addition, there is a need to create clear guidelines for early prostate cancer detection to facilitate optimal care for men prescribed 5-ARIs.”

The American Society of Clinical Oncology and the American Urological Association could not recommend a specific PSA cutoff to trigger a prostate biopsy in 5-ARI users, according to investigators. The National Comprehensive Cancer Network Prostate Cancer Early Detection Guidelines suggest 5-ARIs decrease PSA level by approximately 50% but cite substantial variability.

References

Sarkar RR, Kellogg Parsons J, Bryant AK, et al. Association of treatment with 5α-reductase inhibitors with time to diagnosis and mortality in prostate cancer. JAMA Intern Med. doi:10.1001/jamainternmed.2019.0280

Men taking medications for enlarged prostate face delays in prostate cancer diagnosis [news release]. University of California, San Diego; May 6, 2019.