Long-standing concerns about the consequences of finasteride increasing the risk of high-grade prostate cancer "have not been borne out," report investigators from the landmark Prostate Cancer Prevention Trial (PCPT).
This trial previously indicated that finasteride, a 5-alpha-reductase inhibitor commonly used for benign prostatic hyperplasia and male pattern baldness, is an effective chemopreventive agent for prostate cancer.
However, the drug has never been fully accepted for this use, mainly because earlier results from the trial showed an increased risk of high-grade prostate cancer.
Now, longer-term results from this trial (median follow-up of 18.6 years) show that there has been no increase in prostate cancer-related deaths with the drug, the researchers point out in correspondence published online today in The New England Journal of Medicine.
Such an increase would be expected if finasteride truly caused more high-grade cancers.
"Finasteride is safe, inexpensive, and effective as a preventive strategy for prostate cancer," summarized Ian Thompson Jr, MD, principal investigator of the PCPT and professor emeritus at the University of Texas Health Science Center at San Antonio.
Thompson hopes that physicians give finasteride, which is the only proven method for preventing prostate cancer, a chance in the clinic.
"Doctors should share these results with men who get regular prostate-specific antigen tests that screen for the presence of prostate cancer. The drug will have its greatest effect in this group of men," he said.
New Long-Term Data Show No Increase in Deaths
The story of the PCPT starts in the 1990s, when Thompson and co-trialists randomized more than 18,000 American men ages 55 and older to receive finasteride (5 mg daily) or placebo for 7 years to prevent prostate cancer.
When initial results were first published in 2003, the trial was both a success and a failure.
On the one hand, the risk of prostate cancer with finasteride was 24.8% lower than with placebo.
But at the same time, there was a significant increase in the number of high-grade cancers with the drug compared with placebo (280 vs 237).
This latter finding torpedoed use of the hormone blocker as a cancer prevention agent.
"There is no question that the reason finasteride is not used for prostate cancer prevention is because of the small but statistically significant increase in high-grade disease. Absolutely no question," Thompson told Medscape Medical News at the 2018 annual meeting of the American Urological Association (AUA), where the newly published data were first presented.
This finding has been paradoxical, say Thompson and his coauthors in their correspondence to the NEJM.
So the team initiated a long-term analysis — to see if the increase in high-grade disease resulted in more prostate-cancer related deaths in the finasteride group of the PCPT, as might be expected.
But that's not how it played out. Instead, in the new analysis, there were fewer prostate cancer deaths in the finasteride group than in the placebo group (42 vs 56).
This translated to a 25% lower risk of death from prostate cancer with finasteride compared to placebo in the trial (hazard ratio 0.75, 95% confidence interval [CI] 0.50 - 1.12), which was sponsored by SWOG Cancer Research Network.
"We have no evidence that there's an increase in prostate cancer death in the finasteride arm," Thompson said.
In other words, the initial study findings in 2003 showing an increase in high-grade disease are not consequential 16 years later.
Side Effects Not Mentioned
The newly published letter from the PCPT investigators does not discuss the side effects of finasteride in men. At the AUA meeting, Thompson indicated that more sexual adverse effects have been consistently reported with finasteride than with placebo. However, he described them as "relatively modest."
In affected men, "it's like being maybe 3 years older," he said. The trial also showed, among other side effects, that the risk for gynecomastia was higher with finasteride than with placebo (4.5% vs 2.8%). Notably, the drug has not been shown to improve overall survival.
The chemopreventive agent, which is now generic, is inexpensive, about $48 to $108 a month.
At AUA last year, another urologist endorsed finasteride. "I do use it for some patients, but they tend to have concomitant urinary symptoms," said Scott Eggener, MD, from the University of Chicago.
He said that he discusses finasteride for cancer prevention with some men. "Most guys, when they hear the data, say, 'that sounds good,' " Eggener added.
The sexual adverse effects are concerning, but in his experience and in clinical trials, only a small percentage of men are affected, and problems such as low libido and reduced ejaculate are reversible, Eggener told Medscape Medical News.
The reputation of finasteride — that it increases the risk for high-grade disease — is unfair. "I think it's been completely disproven, given the totality of the research," he said.
The National Cancer Institute and the National Institutes of Health funded the study. Thompson and Eggener have disclosed no relevant financial relationships.
N Engl J Med. Published online January 23, 2019. Full text
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