Men treated with medications for symptoms of benign prostatic hyperplasia (BPH) experienced a two-year delay in diagnosis of their prostate cancer and were twice as likely to have advanced disease upon diagnosis, report University of California San Diego School of Medicine researchers.
Men who took drugs that inhibit the enzyme 5α-reductase, known as 5-ARIs, were diagnosed with prostate cancer 3.6 years after the first signs of elevated levels of a protein called prostate-specific antigen (PSA) compared to 1.4 years for men who did not use 5-ARI. The findings are published in the May 6, 2019 online issue of JAMA Internal Medicine.
"Our study demonstrates how important it is to raise awareness among medical care teams and patients that 5-ARI inhibitors can cause PSA-suppression,” said Brent S. Rose, MD, assistant professor in the Department of Radiation Medicine and Applied Sciences at UC San Diego School of Medicine and senior author on the paper. “In addition, there is a need to create clear guidelines for early prostate cancer detection to facilitate optimal care for men prescribed 5-ARIs.”
Previous studies have shown that treatment with 5-ARIs can result in an approximately 50 percent reduction in the levels of PSA, a protein produced by the prostate gland. Because prostate cancer can cause an increase in PSA levels, the PSA test is used as a screening tool for this cancer type.
Men are prescribed 5-ARI to reduce the effects of BPH, a non-cancerous condition in which the enlarged prostate squeezes or blocks the urethra. This condition affects more than 50 percent of men above the age of 50. It can lead to urinary symptoms, such as difficulty starting or stopping urination and the constant feeling of needing to urinate.
Data from the population-based cohort study of 80,875 men with a PSA-known diagnosis between 2001 and 2015 showed that 29 percent of 5-ARI users had a biopsy performed within two years of first elevated adjusted PSA compared to 59 percent of nonusers.
Twenty-five percent of 5-ARI users were diagnosed with high-grade cancers —malignancies that grow and spread quickly and have a worse prognosis — while 17 percent of nonusers presented with high-grade cancers. In addition, 7 percent of users had metastatic disease compared to 3 percent of nonusers.
"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," said Reith R. Sarkar, clinical research associate in the Department of Radiation Medicine and Applied Sciences and first author on the paper. “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.”
Co-authors include: J. Kellog Parsons, Alex K. Bryant, Stephen T. Ryan, Andrew K. Kader, Rana R. McKay, John P. Einck, Arno J. Mundt, Christopher J. Kane, and James D. Murphy, all at UC San Diego; Anthony V. D’Amico and Paul L. Nguyen, Harvard Medical School; and Benjamin J. Hulley, UC San Diego and Veterans Affairs San Diego Healthcare System.
Funding for this research came, in part, by the National Institutes of Health (TL1TR001443).