Popular drugs used for treating enlarged prostates associated with high-grade prostate cancer

If a man has an enlarged prostate, there’s a good chance he’ll be treated with a type of drug called a 5-alpha reductase inhibitor (5-ARI). These drugs shrink the gland to improve urinary flow, and the approved forms used for treating enlarged prostates come in two varieties: Proscar (finasteride) and Avodart (dutasteride).

However, a side effect of 5-ARI inhibitor treatment is that it suppresses blood levels of prostate-specific antigen (PSA) by about 50%. Doctors measure PSA during prostate cancer screening, and if a man on 5-ARI therapy winds up with results that are artificially low, then he might be falsely reassured that he doesn’t need any additional prostate cancer testing.

A new study with just over 80,000 prostate cancer patients highlights this risk. Men in the study who developed prostate cancer while taking a 5-ARI inhibitor had significant delays in diagnosis compared to nonusers. And because those cancers were discovered at more advanced stages, the men’s outcomes were also comparatively worse. The study was led by Dr. Brent S. Rose, assistant professor in the department of radiation medicine and applied sciences at the University of California, San Diego School of Medicine.

PSA tests raise red flags for cancer when the measured values are 4 nanograms per milliliter (ng/mL) or higher in blood. As a general rule, doctors can double the measured PSA result in men taking a 5-ARI inhibitor to account for the 50% reduction in actual blood levels. So if a man’s test reads 3.5 ng/mL, then the doctor can interpret the value as 7 ng/mL, which would ordinarily trigger a prostate imaging test or a biopsy to look for cancer in the gland.

What the researchers did

Dr. Rose and his colleagues speculated that this doubling occurs infrequently in the general medical community. To investigate, they looked at 80,750 prostate cancer cases documented in the Veterans Affairs database between 2001 and 2015. They focused specifically on differences between men who either were or were not taking 5-ARIs when they were diagnosed with prostate cancer. The men on 5-ARI inhibitors had been taking the drugs for a median of 4.8 years before the prostate cancer was detected.

What they found

According to the study findings, men on 5-ARI inhibitors fared worse in all respects: the time to diagnosis triggered by PSA readings among men using 5-ARI inhibitors was 3.6 years, compared to 1.4 years for nonusers, and there were also statistically higher numbers of high-grade tumors, a higher frequency of cancer in the lymph nodes, and metastatic tumors spreading in the body among men who were taking 5-ARI inhibitors. Lastly, the prostate cancer-specific death rate at 12 years was 13% among 5-ARI inhibitor users, compared to 8% among nonusers and men taking other treatments for enlarged prostates that don’t affect PSA.

Dr. Rose and his colleagues emphasize that the findings don’t mean 5-ARI inhibitors are inherently unsafe, or that PSA screening is ineffective in men who take these treatments. Indeed, other studies have shown no impact on survival for men on 5-ARI inhibitor therapy — and fewer cancer deaths among them compared to nonusers — “but these studies also required strict adjustment of PSA level,” to account for how the drugs suppress PSA levels, the authors wrote.

The authors also admit that they don’t know how many doctors do or do not adjust for PSA suppression among men who take 5-ARI inhibitors. But the new results, they claim, suggest that such adjustments aren’t routinely performed, and that there is a continued need to raise awareness of 5-ARI–induced suppression of PSA, in addition to clear guidelines on how to manage it.

Dr. Marc Garnick, Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of HarvardProstateKnowledge.org, said the findings are disturbing. According to Garnick, 5-ARIs have been extensively studied, and an FDA review panel associated the drugs with an increased risk of higher-grade prostate cancer compared to placebo. “The current study underscores that same finding,” he said. “And whether it is due to a diagnostic delay resulting from lower PSA levels or whether these drugs are affecting the biological behavior of the cancer itself should be a source of continued investigations. In the meantime, these drugs do have good efficacy in controlling the symptoms of an enlarged prostate, and a frank discussion needs to be undertaken with the patient and physician before the prescription is filled.”