title: Modeling and analysis of Gleason score 8-10 prostate cancers in the REDUCE study.
abstract: OBJECTIVE
  To explore explanations for the numerical imbalance of biopsy-detected Gleason 8-10 prostate cancers (PCa) diagnosed in years 3-4 in the dutasteride and placebo groups of the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) study.
  
  
  METHODS
  REDUCE was a 4-year, randomized, double-blind, placebo-controlled trial of dutasteride (0.5 mg/d) vs placebo for PCa risk reduction. We modeled the incidence of Gleason 8-10 cancer and used logistic regression analysis to evaluate the effects of baseline predictors of PCa, as well as post-baseline prostate volume at the time of biopsy, on PCa diagnosis. We compared needle biopsy Gleason scores with corresponding surgery Gleason scores. All statistical tests conducted were 2-sided.
  
  
  RESULTS
  Had there been a scheduled biopsy occurring only at year 4, we estimated a similar incidence of Gleason 8-10 PCa in the dutasteride (n = 45) and placebo (n = 46) groups. Two biopsy Gleason 7 cancers in the placebo group (n = 150) were upgraded to Gleason 8-10 cancer on prostatectomy, and no patients in the dutasteride group (n = 111) were upgraded. Logistic regression analysis demonstrated the effect of prostate volume on Gleason 8-10 cancer diagnosis.
  
  
  CONCLUSIONS
  Although modeling of REDUCE data showed a similar incidence of Gleason 8-10 cancer in the dutasteride and placebo groups at year 4, an association between dutasteride and Gleason 8-10 cancer cannot be definitely excluded. It is likely that several biases, notably study design and prostate size at the time of biopsy, contributed to the numerical imbalance in Gleason 8-10 cancers observed between the treatment groups in years 3-4.
authors.affiliation: Division of Urologic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO. Electronic address: andrioleg@wustl.edu.
authors.forename: Gerald L
authors.initials: GL
authors.lastname: Andriole
authors.affiliation: Bostwick Laboratories, Glen Allen, VA.
authors.forename: David G
authors.initials: DG
authors.lastname: Bostwick
authors.affiliation: Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA.
authors.forename: Leonard G
authors.initials: LG
authors.lastname: Gomella
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Marberger
authors.affiliation: Department of Urology, Scientific Institute Hospital San Raffaele, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.affiliation: Department of Urology, Tampere University Hospital, University of Tampere, Tampere, Finland.
authors.forename: Teuvo L
authors.initials: TL
authors.lastname: Tammela
authors.affiliation: Department of Urology Research, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN.
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Tindall
authors.affiliation: Pharmaceutical Product Development, Wilmington, NC.
authors.forename: Ivy L
authors.initials: IL
authors.lastname: Fowler
authors.affiliation: GlaxoSmithKline, Research Triangle Park, Raleigh-Durham, NC.
authors.forename: Harmony P
authors.initials: HP
authors.lastname: Garges
authors.affiliation: GlaxoSmithKline, Research Triangle Park, Raleigh-Durham, NC.
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Wilson
authors.affiliation: GlaxoSmithKline R&D, King of Prussia, PA.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Castro
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000627:therapeutic use*; D001378:Azasteroids / Q000627:therapeutic use*; D001707:Biopsy, Needle; D000068538:Dutasteride; D006801:Humans; D008297:Male; D015233:Models, Statistical; D060787:Neoplasm Grading; D011471:Prostatic Neoplasms / Q000145:classification* / Q000188:drug therapy* / Q000473:pathology*; D016032:Randomized Controlled Trials as Topic; D013997:Time Factors
chemical_list: D058891:5-alpha Reductase Inhibitors; D001378:Azasteroids; D000068538:Dutasteride