The predictive value of HGPIN and ASAP for the subsequent diagnosis of prostate cancer in the Reduction by Dutasteride of Cancer Events (REDUCE) study.

Abstract

4561 Background: REDUCE was a 4-year, randomized placebo (pbo) controlled study of prostate cancer (PCa) risk reduction with once daily dutasteride 0.5 mg (dut). This analysis examines the effect of dut on initial detection of high-grade prostatic intraepithelial neoplasia (HGPIN) and/or atypical small acinar proliferation (ASAP) and the incidence of PCa on subsequent biopsy. Methods: Eligible men were aged 50–75 years, had a serum PSA 2.5–10.0 ng/ml, and a single, negative (no PCa, HGPIN or ASAP) biopsy of 6–12 cores in the 6 months prior to enrollment (4126 subjects randomized to pbo, 4105 dut). Ten-core prostate biopsies were taken at 2 and 4 years and examined for evidence of PCa. For subjects with 2-year biopsies and no PCa (2866 pbo, 2867 dut), the initial incidence of ASAP, HGPIN (without ASAP), and ASAP or HGPIN was compared between treatment groups using Fisher's exact test. PCa incidence in a subsequent biopsy was also compared between treatment groups with Fisher's exact test. Results: PCa incidence in subjects biopsied was 17.2% (pbo) and 13.4% (dut) in Years 1–2; and 11.8% (pbo) and 9.1% (dut) in Years 3–4. Dut was associated with a lower incidence of ASAP and/or HGPIN (p≤0.007; Table). For subjects with ASAP and/or HGPIN in initial study biopsy who had a subsequent biopsy (median time between biopsies 2 years), the incidence of PCa was higher vs. overall PCa incidence during Years 3–4. If a man was diagnosed with HGPIN or ASAP while taking dut, the likelihood of a future PCa diagnosis was similar to that of the pbo group. Conclusions: HGPIN and ASAP conferred a 2- and 3-fold increased risk of subsequent PCa, respectively compared to the overall rates for PCa in Years 3–4. Dut significantly reduced the incidence of HGPIN and/or ASAP with no significant differences vs. pbo observed in the risk of subsequent PCa. Incidence Pbo Dut p value ASAP 1st dx ASAP 206/2,866 (7.2%) 156/2,867 (5.4%) 0.007 Subsequent PCa 39/116 (33.6%) 29/95 (30.5%) 0.66 HGPIN and no ASAP 1st dx HGPIN 243/2,866 (8.5%) 143/2,867 (5.0%) <0.0001 Subsequent PCa 23/109 (21.1%) 12/63 (19.0%) 0.85 ASAP and/or HGPIN 1st dx ASAP/HGPIN 434/2,866 (15.1%) 288/2,867 (10.0%) <0.0001 Subsequent PCa 61/221 (27.6%) 40/153 (26.1%) 0.81 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca, Bostwick Laboratories, Ferring Pharmaceutical, GlaxoSmithKline Astellas Pharma, GlaxoSmithKline, Orion Pharma Bostwick Laboratories, GlaxoSmithKline Astellas Pharma, Ferring Pharmaceutical, GlaxoSmithKline, Orion Pharma GlaxoSmithKline GlaxoSmithKline