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Finasteride shows long-term safety for prostate cancer prevention
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Finasteride safely prevented prostate cancer, despite previous findings that suggested the drug increased the risk for high-grade disease, according long-term data published in The New England Journal of Medicine.
The latest results report mortality over 2 decades among men in the Prostate Cancer Prevention Trial, which previously found that finasteride reduced risk for prostate cancer by 24.8% compared with placebo.
However, trial results also showed that the drug increased the number of high-grade prostate cancers, leading to a warning label from the FDA. Although additional data showed finasteride improved detection of prostate cancer and high-grade prostate cancer by improving the performance characteristics of PSA testing, digital rectal examination and the prostate biopsy — which could explain the conflicting original results — questions regarding the risk of the drug persisted.
Finasteride, a 5-alpha-reductase inhibitor, also is used to treat lower urinary tract problems and male pattern baldness.
“The men most likely to benefit are those we see in the study — they are 55 years or older and are undergoing PSA testing,” Ian M. Thompson Jr., MD, chair of the genitourinary cancer committee for SWOG Cancer Research Network and president of CHRISTUS Santa Rosa Hospital Medical Center, told HemOnc Today. “The magnitude of the benefit may be greater in men who are at higher risk for prostate cancer, that being a man with a family history or an African-American man. ... But what we found in the original study is that all men — regardless of family history, race, ethnicity and so forth — have a risk reduction.”
Researchers of the trial randomly assigned 18,882 men — enrolled from 1993 to 1997 — to receive finasteride or a placebo for 7 years.
At median follow-up of 18.4 years, 42 men in the finasteride group and 56 men in the placebo group had died of prostate cancer.
The 25% lower risk for prostate cancer death with finasteride was not statistically significant (HR = 0.75; 95% CI, 0.5–1.12).
However, Thompson said the results eliminate concerns about the possible risk for more aggressive cancers with finasteride, which he described as an inexpensive and reliable prostate cancer prevention drug.
He said that he is unaware of a clear process that would take the warning label off the drug.
“But it’s not just changing the warning. It’s also putting in the label that this drug results in an unequivocal reduction in the risk for cancer,” Thompson told HemOnc Today. “This is really a big deal. ... If we had known this at the time the study was originally published, my suspicion is that many or most men who are [aged] 55 years or older would be taking this medication. But because it had a stain on it ... it’s kind of like a sticky fact. The trick will be helping the community get rid of that sticky fact and go back to this original discovery.
“This is the most common cancer in men,” Thompson added. “If men at risk for prostate cancer took this, we could eliminate 40,000 to 50,000 prostate cancer [diagnoses] a year, and that’s a huge deal from a cost and suffering standpoint.” – by John DeRosier
For more information:
Ian M. Thompson Jr., MD, can be reached at: ian.thompson2@christushealth.org.
Disclosures: The NCI and NIH funded this study. Thompson reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
Perspective
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The recent correspondence in The New England Journal of Medicine by Thompson and colleagues details long-term follow-up of the Prostate Cancer Prevention Trial, with particular focus on cumulative incidence of prostate cancer-related death. The trial, originally published in 2003, tested the use of finasteride among men aged 55 years or older as a primary prevention strategy for prostate cancer.
Finasteride was associated with a significant reduction in risk for prostate cancer. However, an associated increase in the diagnosis of intermediate- and high Gleason-grade tumors — with an unknown effect on long-term survival — halted its widespread adoption in clinical practice.
For patients and practitioners, the recently reported findings showing no significant difference in the risk for death of prostate cancer, with a median follow-up of nearly 20 years, is certainly informative. We are now more confident that the increase in nonindolent tumors in the treatment arm of the trial was the result of differences in clinical evaluation (eg, PSA levels, physical examination, prostate biopsy interpretation) influenced by finasteride, as opposed to direct induction of more aggressive disease subtypes by finasteride.
What remains less clear is how we should integrate these findings into practice as we develop personalized approaches to prostate cancer screening and prevention. Prevention strategies should balance relative and absolute benefit against the burdens of treatment in the context of the individual patient. Although finasteride is a widely used agent for urinary symptoms and male pattern baldness, it is associated with sexual and endocrine side effects that may outweigh the prevention benefit. This is particularly true for men who are at low risk for clinically significant (intermediate- or high-grade) prostate cancer.
Although finasteride reduced the risk for prostate cancer, it appeared most effective in reducing the incidence of low-risk disease — the form of prostate cancer that often does not require morbid, curative treatments. This is consistent with the lack of an observable difference in prostate cancer-specific death. A key question, therefore, is how the potential side effects of long-term finasteride therapy are balanced against the effects, both physical and psychological, of a diagnosis of low-risk prostate cancer and its subsequent management. It should also be explained that the trial prescribed frequent monitoring, and this may not reflect real-world practice nor be desirable to some patients.
Lastly, whether an optimal age and duration of therapy exist remains unknown.
The long-term results of the Prostate Cancer Prevention Trial add valuable information to our understanding of finasteride as a preventative agent for prostate cancer and should ultimately continue to inform a nuanced discussion of the benefits and risks of therapy.
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