1249 STATINS SLOW PROSTATE GROWTH: RESULTS FROM THE REDUCTION BY DUTASTERIDE OF CANCER EVENTS (REDUCE) TRIAL

Vol. 187, No. 4S, Supplement, Monday, May 21, 2012

THE JOURNAL OF UROLOGY姞

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the dutasteride arms (5.0% decrease in PV growth, P⬍0.001). However, after adjusting for multiple confounders, statin use was not associated with PV growth from the 2- to 4-year time in either the placebo (0.0% change PV growth, P⫽0.52) and dutasteride arms (0.0% change in PV growth, P⫽0.64). CONCLUSIONS: In men with an elevated PSA and a negative prostate biopsy, statin use was associated with a modest reduction in PV growth, which occurs within 2-years with no further reductions over the next 2 years. The degree of PV growth reduction (⬃4%) is consistent with our prior results that statins reduce PSA levels by 4.1% suggesting the declines in PSA in our prior study may be due to reductions in PV. Further prospective studies are needed to confirm these findings as well as to understand the mechanisms by which statins reduce PV. Source of Funding: Supported by GlaxoSmithKline

1250 THE ROLE OF DUTASTERIDE IN PREVENTING BPH CLINICAL PROGRESSION IN ASYMPTOMATIC MEN WITH AN ENLARGED PROSTATE Paul Toren*, David Margel, Girish Kulkarni, Antonio Finelli, Alexandre Zlotta, Neil Fleshner, Toronto, Canada

Source of Funding: GlaxoSmithKline

1249 STATINS SLOW PROSTATE GROWTH: RESULTS FROM THE REDUCTION BY DUTASTERIDE OF CANCER EVENTS (REDUCE) TRIAL Roberto Muller*, Leah Gerber, Durham, NC; Daniel Moreira, New Hyde Park, NY; Gerald Andriole, Saint Louis, MO; J. Kellogg Parsons, San Diego, CA; Neil Fleshner, Toronto, Canada; Stephen Freedland, Durham, NC INTRODUCTION AND OBJECTIVES: Statins are cholesterollowering agents with anti-inflammatory and apoptotic properties. We previously found starting a statins was associated with 4.1% reduced PSA levels within 1 year and, given PSA correlates with prostate volume (PV), we hypothesized statins may affect PV. Indeed, a study of 416 men with PV⬍30mL and PV measured serially by transrectal ultrasound (TRUS) over many years found statin use reduced the risk of a PV ⬎30mL. However, a 6-month trial of atorvastatin vs. placebo showed no effect on PV. We tested if statins were associated with PV changes in REDUCE, a 4-year randomized trial of dutasteride vs. placebo for prostate cancer prevention wherein TRUS PV was obtained from mandated on-study biopsies regardless of PSA. METHODS: Men were aged between 50-75 yrs, had a PSA between 2.5-10 ng/mL, a prior negative prostate biopsy, and a prestudy PV of ⬍80cc. PV was obtained from TRUS at 2- and 4-year biopsies and compared to baseline. Of 8122 men in the efficacy population, after excluding PV after prostatic surgery, 6423 men (79.1%) had serial PV data, of which we excluded 330 (5.1%) due to missing data or extreme PV change from baseline. Statin use was assessed at baseline. We used multivariable linear regression to test if statin use was associated with PV changes at 2- and 4-years stratified by placebo and dutasteride arms. Models were adjusted for confounders. RESULTS: Of 6093 men, 1032 used statins at baseline (16.9%). They were older (63.3 vs. 62.7 years, P⫽0.001) but had similar baseline PV (P⫽0.55) vs. non-statin users. At 2-years, after adjusting for multiple confounders, prostate growth was less for statin users in both the placebo (3.9% decrease in PV growth, P⫽0.02) and

INTRODUCTION AND OBJECTIVES: Benign prostatic hypertrophy (BPH) commonly causes lower urinary tract symptoms (LUTS) among men as they age. Treatment with 5-alpha reductase inhibitors has been studied in men with moderate-severe LUTS. Although a relationship exists between prostate size and LUTS, it is not absolute and variability exists. Prostatic enlargement, however, is a risk factor for events such as acute urinary retention (AUR) and need for surgery, as well as development of clinical symptoms. Our study aims to assess the role of dutasteride in preventing clinical progression in asymptomatic or mildly symptomatic men with larger prostates using data obtained from the REDUCE study. METHODS: Using data obtained from the REDUCE study, we assessed the outcomes of men with a prostate size ⬎40 mL and baseline International Prostate Symptom Score (IPSS) ⬍8. Men treated with any medications for BPH at time of study entry or who did not complete the end-of-study IPSS questionnaire were excluded. We compared the risk of BPH clinical progression at four years between those randomized to dutasteride versus placebo. BPH clinical progression was defined as a ⬎4 point worsening on IPSS, AUR related to BPH, urinary tract infection, or BPH related surgery. A multivariable logistic regression assessed the effect of dutasteride on BPH clinical progression adjusting for age and baseline variables (IPSS, prostate volume, post-void residual, and peak urinary flow rate). Adverse effects were assessed. RESULTS: Our study cohort consisted of 1617 men; 825 on placebo, 792 on dutasteride. A total of 464 patients (29%) experienced BPH clinical progression; 297(36%) on placebo, 167(21%) on dutasteride (P⬍0.001). The relative risk reduction was 44% and the absolute risk reduction was 15%, with a number needed to treat(NNT) of 7. Seventy-six patients (4.7%) had AUR: 63 on placebo and 13 on dutasteride (P⬍0.001). Forty-six patients had BPH related surgery: 29 on placebo and 7 on dutasteride (P⬍0.001). On multivariable logistic regression analysis, dutasteride significantly reduced BPH clinical progression with an odds ratio of 0.47(95% CI 0.37-0.59, P⬍0.001). The most common drug-related adverse effects were erectile dysfunction, at 5.1% and 9.0%(P⫽0.02) and decreased or no libido, at 2.3% and 6.8% (P⬍0.001) in the placebo and dutasteride arms, respectively. CONCLUSIONS: This study is the first to explore the benefit of treating asymptomatic or mildly symptomatic men with enlarged prostates. In this cohort, dutasteride significantly decreased the incidence of BPH clinical progression over 4 years, with a NNT of 7. Source of Funding: None