PCPT Trial Helps Confirm Role of 5α-Reductase Inhibitors in Prostate Cancer Prevention

Tracey Regan
Published: Tuesday, Dec 17, 2013
Gerald L. Andriole Jr.

Gerald L. Andriole Jr, MD


Robert K. Royce Distinguished Professor
Chief, Division of Urologic Surgery
Barnes-Jewish Hospital
Siteman Cancer Center
Washington University School of Medicine
St. Louis, MO

Two years after the FDA denied a request to expand the indication of finasteride and other 5α-reductase inhibitors to prevent prostate cancer, a major study has cast doubt on the concerns that prompted the denial: that the drug raised the risk of more lethal cancers. Results from an 18-year follow-up study1 of the National Cancer Institute’s landmark Prostate Cancer Prevention Trial (PCPT), which evaluated the drug’s safety and efficacy, found a slightly higher rate of high-grade cancers among the men taking finasteride but no difference in survival rates between treated men and those in the placebo arm, even among men with a high-grade cancer diagnosis (Figure).

The analysis showed that finasteride reduced the risk of low-grade prostate cancer by about one-third. Yet, the drug has seen little use in cancer prevention since the initial report, published in 2003, which found that it reduced the risk of prostate cancer by about 25%, but increased the risk of high-grade cancer by about the same amount. Those findings sparked debate over whether the drug caused more serious cancers or made it easier to detect them. In the latest analysis, Thompson et al collected data on the incidence of prostate cancer among PCPT participants and then searched the Social Security Death Index to assess survival status through October 2011.

Although this follow-up study may have allayed some concerns about finasteride, it remains unclear whether clinicians will now use the drug as a cancer prevention tool. Proponents of cancer prevention with finasteride and other 5α-reductase inhibitors are reassured by these findings but other considerations, such as the reduced emphasis on prostate-specific antigen (PSA) screening and the need for clinicians to use PSA differently in men receiving these agents, may result in little change in the use of these medications. These drugs remain approved and widely prescribed as treatments for benign prostatic enlargement, however, and use for that indication may well rise.

For more than a decade, Gerald L. Andriole Jr, MD, of Barnes-Jewish Hospital and the Siteman Cancer Center, has been conducting research into the optimal use of finasteride and other 5α-reductase inhibitors. In this interview with OncologyLive, Andriole discusses the implications of the latest finasteride findings.

OncologyLive: Does finasteride have a role in cancer prevention going forward?

I think it does, and I think it should be used selectively for this purpose. If a man is going to be screened with PSA, I think that 5α-reductase inhibitors will improve the overall effectiveness of screening for two reasons: They reduce the diagnosis of low-grade cancers that do not warrant treatment and they improve the ability of PSA to detect more aggressive cancer. Reducing the diagnosis of trivial cancers is important, as a major problem with screening is overtreatment of lowgrade cancers. This causes real harm to patients as they may experience side effects from treatment while getting no benefit from it.

Finasteride also makes PSA a better marker for aggressive cancers. For men taking [finasteride], PSA initially falls. If PSA subsequently rises above the nadir, then that is a strong signal that an aggressive cancer may be developing. The interpretation of PSA is different for men taking this drug. While urologists are sensitized to these nuances, many primary care providers and family doctors may not know that a rising PSA for men receiving finasteride, even if it is still under 4, is not normal and is a serious warning sign that an aggressive cancer may be developing. The potential for misinterpretation of PSA in this way was one of the reasons the FDA decided not to modify the label.

How should clinicians interpret the updated results of the PCPT?

Individuals who were concerned that finasteride use promoted aggressive prostate cancer should find reassurance from this analysis. The results show that the drug is safe if patients are closely monitored and PSA is interpreted correctly. But will that message get out to primary care physicians? I doubt it. Will they prescribe it for prostate cancer prevention? Probably not. It’s a complicated issue in which they hear that experts disagree, and there is a movement against widespread PSA screening at the moment anyway. This drug is most beneficial for men at higher risk of prostate cancer who should be getting screened. On the other hand, use of this drug for men with benign prostatic hyperplasia [BPH] could well increase.

How has finasteride’s use evolved over time?

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