5-alpha Reductase Inhibitors Help Prostate Cancer Patients on Active Surveillance

Antonio Finelli, MD

Men with low-risk prostate cancer who have opted for a strategy of active surveillance are about half as likely to experience pathologic progression or abandon active surveillance if they take a 5-alpha reductase inhibitor (5-ARI) as men who are not taking a 5-ARI, Canadian researchers announced at the European Association of Urology (EAU) 27th Annual Congress held in Paris in February.

Antonio Finelli, MD, University Health Network, Princess Margaret Hospital, Toronto, Ontario, Canada, and colleagues reviewed outcomes in men who were taking a 5-ARI while on active surveillance for prostate cancer and men who were not undergoing 5-ARI treatment.

More than 200,000 new cases of prostate cancer were diagnosed in the United States in 2010, and low-risk prostate cancer accounted for roughly half of the new diagnoses, Finelli said. Active surveillance is gaining traction in this population, given that surgery and radiation have an adverse impact on quality of life. Both the National Comprehensive Cancer Network and the National Institute for Health and Clinical Excellence have recommended that active surveillance be considered a first-line strategy for patients with low-risk disease, he said.

Treatment with 5-ARIs inhibits the conversion of testosterone to dihydrotestosterone, which drives both benign and malignant growth of prostatic tissue, Finelli said. These drugs, which are indicated for the treatment of benign prostatic hyperplasia, were associated with a roughly 25% relative reduction in prostate cancer diagnoses compared with placebo in two large randomized, controlled trials. However, no studies to date have demonstrated an effect for 5-ARIs on individuals diagnosed with low-risk prostate cancer.

The study included men with a prostate-specific antigen (PSA) <10 ng/mL, clinical stage T1c/T2a, Gleason score ≤6, and ≤3 cores positive cores with no more than 50% of a core involved at initial diagnostic biopsy. The primary endpoint of pathologic progression was defined as Gleason score >6, or maximum core involvement >50% or >3 positive cores on a follow-up prostate biopsy.

A total of 288 men on active surveillance satisfied the inclusion criteria. The median follow-up was 38.5 months. Overall, 93 men (32%) experienced pathologic progression and 96 men (33%) abandoned active surveillance. Only 13 (18.6%) of 70 men taking a 5-ARI had pathologic progression versus 80 (36.7%) of 218 men not taking a 5-ARI (P = .004).

The median time to progression was longer in the 5-ARI group than the non-5-ARI group (42.5 months vs 31.5 months; P < .026). The 5-ARI group was also less likely to abandon active surveillance (20% vs 37.6%; P = .006).

On multivariate analysis, lack of 5-ARI use was the strongest predictor of pathologic progression (odds ratio [OR], 2.98; 95% CI, 1.5—5.9), followed by age and baseline maximum percentage involvement of any biopsy core.

Finelli said that study limitations included its retrospective design and the lack of uniform duration of 5-ARI therapy or type of 5-ARI used. He added that these findings are supported by the double-blind, placebo-controlled Reduction by Dutasteride of Clinical Progression Events in Expectant Management of Prostate Cancer (REDEEM) trial, which was recently published in The Lancet.

Finelli A, Trottier G, Lawrentschuk N, et al. 5-alpha reductase inhibitors diminish the rate of progression in men with low risk prostate cancer on active surveillance. Presented at the European Association of Urology 27th Annual Congress; February 24-28, 2012; Paris, France. Abstract 1092.