5-alpha-reductase inhibitors not efficacious for secondary prevention of prostate cancer

May 15, 2012

Observational data fail to support a role of 5-alpha-reductase inhibitors (5-ARIs) for secondary prevention of clinically significant prostate cancer in men with very low-risk disease.

Key Points

Baltimore-Observational data fail to support a role of 5-alpha-reductase inhibitors (5-ARIs) for secondary prevention of clinically significant prostate cancer in men with very low-risk disease.

The use of 5-ARIs did not delay cancer reclassification, as defined by unfavorable annual biopsy, in men with no use of 5-ARIs before their prostate cancer diagnosis who were enrolled in an active surveillance program, said first author Ashley E. Ross, MD, PhD, a urology resident at Johns Hopkins University, Baltimore, MD, working with Edward M. Schaeffer, MD, PhD, and colleagues.

In two randomized placebo-controlled clinical trials-the Prostate Cancer Prevention Trial (which studied finasteride [Proscar]) and the Reduction by Dutasteride [Avodart] of Prostate Cancer Events-the use of 5-ARIs has been shown previously to reduce the detection of low-grade primary prostate cancer through serial biopsy, but the incidence of high-grade disease increased among 5-ARI users compared to placebo. After a review of these findings, the FDA did not approve labeling to allow 5-ARIs to be used for the primary prevention of prostate cancer.

"The thought was that these drugs, because they act like a weaker form of hormonal suppression, could prevent the growth of low-grade lesions," Dr. Ross told Urology Times. "In indolent disease, the hope was that you could prevent it from becoming clinically significant with the use of 5-ARIs."

The surveillance cohort included 587 men with clinical stage T1c cancer, a PSA density less than 0.15 ng/mL/cc, Gleason score of 6 or less, fewer than three positive biopsy cores, and 50% or less involvement of each core with tumor. Men in the program were monitored twice yearly with digital rectal examination and PSA measurement, and yearly with 12- or 14-core prostate biopsy.

Forty-seven men started 5-ARIs exclusively for the treatment of lower urinary tract symptoms (with the exception of one man who started finasteride to prevent hair loss) after they had been on active surveillance for a mean of 2.4 years. Men who initiated 5-ARIs had significantly larger prostates and higher PSA levels at the time their cancer was diagnosed. These men were also significantly more likely to use alpha-blockers than non-users of 5-ARIs.

Reclassification was based on unfavorable biopsy characteristics (Gleason pattern ≥4 or cancer in three or more cores or involving >50% of any one core).

A similar retrospective study from Canada that did not account for the length of time that a man was on a 5-ARI or the length of time on surveillance before initiating a 5-ARI demonstrated a dramatic decrease in reclassification among 5-ARI users compared to non-users, said Dr. Ross, who presented his group's findings at the 2011 AUA annual meeting in Washington.

When the same type of crude analysis was done in the Johns Hopkins cohort, it also appeared that 5-ARIs were protective (users were less likely than non-users to have their cancer reclassified). But as with the Canadian retrospective study, this type of analysis is flawed because it does account for timing and duration of 5-ARI exposure, Dr. Ross said.