title: Dutasteride for the prevention of prostate cancer in men with high-grade prostatic intraepithelial neoplasia: results of a phase III randomized open-label 3-year trial.
abstract: OBJECTIVE
  High-grade prostatic intraepithelial neoplasia (HGPIN) is a potential precursor of prostate cancer (PCa), and patients with HGPIN are at high risk for PCa development. Objective of our study was to evaluate the efficacy of dutasteride 0.5 mg in PCa prevention among men with isolated HGPIN on biopsy.
  
  
  METHODS
  This prospective, randomized, phase III, open-label 3-year trial assessed dutasteride versus active surveillance in patients with HGPIN. Patients were randomized to dutasteride 0.5 mg daily or active surveillance. Per-protocol prostate biopsies were performed at 6, 12, 24, and 36 months until cancer detection or study end. The primary end point was cancer-free survival (CFS). An intention-to-treat analysis was done for patients who underwent at least one per-protocol biopsy. An efficacy analysis was done for patients who completed the study. CFS was evaluated using Kaplan-Meier and log-rank analysis.
  
  
  RESULTS
  In total, 220 men were randomized (dutasteride, n = 107; surveillance, n = 113). PCa was detected in 47.6: 49.1 % in the surveillance group and 45.9 % in the treatment group (p = 0.66). The detected PCa differentiation by Gleason score (GS) was GS 6 in 76.9 %, GS 7 in 19.8 %, and GS ≥ 8 in 3.3 %, with no difference between groups. The 3-year PCa-free survival was 43.6 % in the surveillance and 49.6 % in the dutasteride group (log rank p = 0.57). Limitations include a relatively high non-adherence rate, open-label design, and baseline sextant biopsy scheme.
  
  
  CONCLUSIONS
  Dutasteride 0.5 mg for 3 years did not lower the PCa detection rate but did not worsen detected PCa characteristics in men with HGPIN.
authors.affiliation: Department of Urology, Lithuanian Health Science University, Eiveniu 2, 50009, Kaunas, Lithuania. daimantas.milonas@kaunoklinikos.lt.
authors.forename: Daimantas
authors.initials: D
authors.lastname: Milonas
authors.affiliation: Department of Urology, Lithuanian Health Science University, Eiveniu 2, 50009, Kaunas, Lithuania.
authors.forename: Stasys
authors.initials: S
authors.lastname: Auskalnis
authors.affiliation: Department of Urology, Lithuanian Health Science University, Eiveniu 2, 50009, Kaunas, Lithuania.
authors.forename: Giedrius
authors.initials: G
authors.lastname: Skulcius
authors.affiliation: Department of Pathology, Lithuanian Health Science University, Kaunas, Lithuania.
authors.forename: Inga
authors.initials: I
authors.lastname: Gudinaviciene
authors.affiliation: Department of Urology, Lithuanian Health Science University, Eiveniu 2, 50009, Kaunas, Lithuania.
authors.forename: Mindaugas
authors.initials: M
authors.lastname: Jievaltas
authors.affiliation: Department of Urology, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Steven
authors.initials: S
authors.lastname: Joniau
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000627:therapeutic use*; D000368:Aged; D001706:Biopsy; D002277:Carcinoma / Q000473:pathology / Q000517:prevention & control*; D000068538:Dutasteride / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D019048:Prostatic Intraepithelial Neoplasia / Q000188:drug therapy* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*
chemical_list: D058891:5-alpha Reductase Inhibitors; D000068538:Dutasteride
keywords: Chemoprevention; Dutasteride; High-grade prostatic intraepithelial neoplasia; Prostate cancer