Innovation in the medical treatment of advanced prostate cancer

Abstract

Background: Using data from the 4-year REDUCE study we explored the effect of dutasteride on PSA sensitivity and specificity for prostate cancer (PCa) detection. By inhibiting PSA synthe- sis in benign prostate tissue and low-grade PCa, dutasteride may enhance the utility of PSA in diagnosing PCa, particularly high-grade PCa. Methods: REDUCE was a 4-year, randomized, double-blind, placebo-controlled study evaluating the efficacy and safety of dutasteride in PCa risk reduction in men aged 50—75 years with a serum PSA 2.5—10.0 ng/mL and a single prior negative prostate biopsy. The primary endpoint result at 4 years has been reported. Here we compare PCa sensitivity and specificity profiles in dutasteride- and placebo- treated men for the initial decline in PSA, final PSA before biopsy and change in PSA (from Month 6 to final PSA) by calculating area under the curve (AUC) values from receiver operating characteristic (ROC) curves for both treatment groups, separately. Results: Analyses included 3303 men (81.6%) in the dutasteride group and 3423 men (84.1%) in the placebo group, who underwent at least one study biopsy. Following 6 months of dutasteride, similar reductions in mean PSA were observed in men with no cancer, Gleason score 5—6 PCa and Gleason score 7—10 (high-grade) PCa (47.0%, 45.4% and 46.3% decrease, respectively). There- after, for both arms, PSA was highest in men with high-grade PCa, whereas PSA was similar among men with low-grade or no cancer. Final and change from Month 6 to final PSA per- formed better in men who received dutasteride vs. placebo for overall PCa diagnosis (AUC 0.624 vs. 0.572, p = 0.0017; 0.637 vs. 0.529, p < 0.0001, respectively) and Gleason score 7—10 PCa diag- nosis (0.700 vs. 0.650, p = 0.0487; 0.699 vs. 0.593; p = 0.0001, respectively). In men who received dutasteride, any increase in PSA from Month 6 to final was associated with a higher likelihood of biopsy detectable PCa, Gleason score 7—10 PCa, and higher mean tumor volume on biopsy, compared with no increase in PSA. Conclusion: Dutasteride enhances the utility of PSA for PCa detection, particularly high-grade PCa, in men at increased risk for this disease but with a previous negative biopsy. The ini- tial decrease in PSA with dutasteride does not predict the presence or grade of PCa; however, any subsequent increase in PSA from Month 6 in men taking dutasteride can identify men at increased risk of PCa overall and high-grade tumors, who would therefore benefit from confir- matory biopsy.