Dutasteride (Avodart) reduces the risk of biopsy-detectable prostate cancer by about one-fourth in men at high risk for the disease without increasing the risk of high-grade cancers. In addition, the 5-alpha-reductase inhibitor significantly enhances the utility of PSA as a diagnostic test for prostate cancer.
REDUCE was a 4-year, international, multicenter, parallel-group study in which 8,200 men with a PSA level of 2.5 to 10.0 ng/mL (age 50 to 60 years) or 3.0 to 10.0 ng/mL (>60 years) were randomized to dutasteride or placebo. All men had a single, negative prostate biopsy (six to 12 cores) within 6 months prior to study enrollment, and prostate volume was restricted to 80 cc or less to be eligible.
Over the course of the 4-year study, treatment with dutasteride resulted in a 23% relative risk reduction in biopsy-detectable prostate cancer versus placebo (p<.0001). The relative risk reduction with dutasteride was consistent across pre-specified subgroups based on age, family history of prostate cancer, International Prostate Symptom Score, prostate volume tertiles, and PSA tertiles.
Rates of Gleason score 7 to 10 cancers were 6.8% in the placebo group and 6.7% in the dutasteride group; the rates of Gleason score 8 to 10 prostate cancers were 0.6% and 0.9% in the placebo and dutasteride arms, respectively.
The incidence of Gleason 5 or 6 tumors was 18.1% in the placebo recipients and 13.3% in the dutasteride recipients (p<.0001).
"We've learned from some analyses in the last few years that quite a significant proportion of Gleason 5 and 6 cancers will actually harbor Gleason 7 to 10 components that were not discovered by the biopsy. We also learned that in a placebo-treated man, the probability of such upgrading is more likely than in a man receiving a 5-alpha-reductase inhibitor because his prostate is smaller and his biopsies tend to be more accurate," Dr. Andriole said.
"I think we have substantial reassurance, given that there are more Gleason 5 or 6 cancers eligible to be upgraded in the placebo group, and since the probability of such upgrading is higher in the placebo group than in the dutasteride group, we should be very confident that there is no increase in high-grade tumors over the 4 years of the REDUCE trial."
There was a 39% relative reduction (p<.0001) in the occurrence of high-grade prostatic intraepithelial neoplasia and a 21% relative reduction (p=.04) in atypical small acinar proliferation with randomization to dutasteride.
In men assigned to dutasteride, the number of positive cores was lower for all tumors, including high-grade tumors, and the proportion of cores involved with cancer was lower, including the high-grade tumors.
"If you transform these parameters into an estimate of volume of cancer on biopsy, the tumors in the dutasteride arm appeared smaller, and this included the high-grade tumors," said Dr. Andriole.