Modeling and analysis of Gleason score 8-10 prostate cancers in the REDUCE study.

Author(s): Andriole GL(1), Bostwick DG(2), Gomella LG(3), Marberger M(4), Montorsi F(5), Tammela TL(6), Tindall DJ(7), Fowler IL(8), Garges HP(9), Wilson TH(9), Castro R(10).

Affiliation(s): Author information: (1)Division of Urologic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, MO. Electronic address: andrioleg@wustl.edu. (2)Bostwick Laboratories, Glen Allen, VA. (3)Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA. (4)Department of Urology, Medical University of Vienna, Vienna, Austria. (5)Department of Urology, Scientific Institute Hospital San Raffaele, Milan, Italy. (6)Department of Urology, Tampere University Hospital, University of Tampere, Tampere, Finland. (7)Department of Urology Research, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, MN. (8)Pharmaceutical Product Development, Wilmington, NC. (9)GlaxoSmithKline, Research Triangle Park, Raleigh-Durham, NC. (10)GlaxoSmithKline R&D, King of Prussia, PA.

Publication date & source: 2014, Urology. , 84(2):393-9

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. CONCLUSION: 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.