SAN FRANCISCO — Will a presentation here at the American Urological Association (AUA) 2018 Annual Meeting be a turning point in the reputation — and use — of finasteride for the prevention of prostate cancer?
Ian Thompson, MD, hopes so.
The eminent urologist and researcher reported, during a plenary session, that the daily use of finasteride, the commonly prescribed hormone-blocking agent, does not elevate the long-term risk for prostate cancer death.
"Very long-term follow-up" shows that finasteride "is safe," Thompson, who is professor emeritus at the University of Texas Health Science Center at San Antonio, said in a press statement.
"These results are transformational," he explained. "We have found an inexpensive, effective drug that can prevent [prostate cancer]."
The new findings about prostate cancer deaths, from the landmark Prostate Cancer Prevention Trial (PCPT), might seem incongruous at first.
After all, finasteride was so effective in reducing the risk for prostate cancer in that study that the placebo-controlled PCPT was stopped early and the results were published in 2003 in the New England Journal of Medicine.
But that is also when the troubles began, because the investigators simultaneously reported an increase in the number of high-grade cancers with the drug, compared with placebo (280 vs 237).
That finding irreparably tarnished finasteride, said Thompson, who is principal investigator of the PCPT.
"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.
But new data address this old finding.
If high-grade disease is more common with finasteride than with placebo, "there should be more prostate cancer deaths [with finasteride]," he explained.
But that's not what the researchers found in their new analysis. Instead, there were fewer prostate cancer deaths in the finasteride group than in the placebo group (42 vs 56).
The median follow-up was 18.4 years, and the cumulative follow-up was almost 300,000 years.
"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 about an increase in high-grade disease are not consequential.
The new data took 5 years to gather, Thompson reported.
PCPT investigators matched more than 18,000 trial participants to the National Death Index, a centralized database of American death records. With this painstaking process, they were able to determine whether a trial participant had died and, if so, the cause of death.
The lion's share of this laborious work was performed by Phyllis Goodman, MS, a biostatistician at the Fred Hutchinson Cancer Research Center in Seattle, who is a member of the PCPT team, Thompson noted.
With these latest data, which come 25 years after the PCPT trial was started, "we have answered the questions and closed the book," Thompson said. It was in 1994, when he was just 39 years old, when he was named principal investigator of the study.
The PCPT is "one of the most powerful and important cancer prevention trials ever conducted," said Joseph Smith, MD, editor of the Journal of Urology, when he introduced Thompson at the plenary session.
The trial, sponsored by the Southwest Oncology Group, was designed to determine whether daily finasteride for 7 years would prevent prostate cancer in men older than 55 years. The first 5-alpha-reductase inhibitor — which targets and blocks the action of androgens, including testosterone — is approved to treat the symptoms of prostate enlargement and male pattern baldness.
As reported in 2003, the risk for prostate cancer over the initial 7-year study period was 25% lower with finasteride than with placebo. That risk reduction now "goes out to 16 years, at least," said Thompson.
However, more "relatively modest" sexual adverse effects have been consistently reported with finasteride than with placebo.
In affected men, "it's like being maybe 3 years older," he told the AUA audience. The trial also showed that the risk for gynecomastia was higher with finasteride than with placebo (4.5% vs 2.8%). And, notably, the drug has not been shown to improve overall survival.
A New Day? Two Doctors Comment
There is an "astonishing" level of interest in the prevention of prostate cancer, said Thompson. Clinicaltrials.gov has a long list of agents under investigation, such as metformin, statins, aspirin, and green tea.
But none of the studies, which are all relatively small, will ever be as authoritative as the PCPT. "You can prevent a quarter of all prostate cancers with finasteride," he pointed out.
"Who uses it today? Almost nobody," said Thompson.
The chemopreventive agent, which is now generic, costs about $48 to $108 a month.
"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 he will discuss finasteride for prevention with some men. "Most guys, when they hear the data, say, 'that sounds good'," he 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.
In another PCPT study, after 18 years of follow-up, no difference in overall survival was seen between the finasteride and placebo groups (N Engl J Med. 2013;369:603-610). This is also evidence that the high-grade cancer disparity is of no consequence.
However, by that time, the black-box warning issued by the US Food and Drug Administration had destroyed the reputation of finasteride.
Some of Eggener's comments were echoed by Robert Abouassaly, MD, from the Cleveland Clinic.
"I use it when there is another indication, such as urinary symptoms," he told Medscape Medical News, but he does not use it at all for prevention.
However, the data Thompson presented could have had a positive impact.
"The new data may shift the urology community's opinion of the risk–benefit ratio for prevention of prostate cancer," Abouassaly said. "The risks are minimal and the sexual side effects are reversible."
Now, when speaking with a patient about finasteride for prevention, "especially if sexual health is not a high priority, I may put more emphasis on the morbidity and mortality of prostate cancer," he noted. It is especially appropriate for men who are at higher risk for prostate cancer, such as those with a family history.
Abouassaly then gave finasteride — and the concept of prostate cancer prevention — high praise: "Looking at the data today, I would consider taking finasteride daily."
The effect of the initial high-grade cancer finding is a "sticky fact," said Thompson.
"It stuck since the first publication and, despite compelling evidence that the drug actually improves the detection of cancer and high-grade disease [because it shrinks the gland, making detection easier], it remains sticky," he explained. "It will be interesting to see whether you can unstick a fact."
The National Cancer Institute and the National Institutes of Health funded the study. Dr Thompson, Dr Eggener, and Dr Abouassaly have disclosed no relevant financial relationships.
American Urological Association (AUA) 2018 Annual Meeting. Presented May 19, 2018.
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Cite this: New Data: Finasteride Safely Prevents Prostate Cancer - Medscape - May 20, 2018.