@article{1f4dadf071fe4ea9a90346cb5c906e29,
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. 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.",
author = "Andriole, {Gerald L.} and Bostwick, {David G.} and Gomella, {Leonard G.} and Michael Marberger and Francesco Montorsi and Tammela, {Teuvo L.} and Tindall, {Donald J.} and Fowler, {Ivy L.} and Garges, {Harmony P.} and Wilson, {Timothy H.} and Ramiro Castro",
note = "Funding Information: Financial Disclosure: Dr. Gerald L. Andriole served as the Chairman of the Steering Committee for the REDUCE trial. He is a paid consultant for Augmenix, Bayer, Genomic Health, GlaxoSmithKline, and Myriad Genetics. He is a study investigator for Johnson & Johnson, Medivation, and WILEX. David G. Bostwick is the owner of Bostwick Laboratories and AIBiotech. Leonard G. Gomella is a member of the Steering Committee for the REDUCE trial. He is also a member of the advisory boards for Abbott, Astellas Pharma, Bayer, Dendreon, Janssen, and Photocure. Michael Marberger is a study participant, speaker, and consultant for GlaxoSmithKline. Francesco Montorsi is a speaker for GlaxoSmithKline. Teuvo Tammela receives funding from GlaxoSmithKline to institution for the REDUCE trial. He is a consultant for Amgen, Astellas Pharma, GlaxoSmithKline, Orion Pharma, and Pfizer. He is also a speaker for Abbott, Amgen, and GlaxoSmithKline. Ivy Fowler is a previous GlaxoSmithKline employee. Harmony P. Garges, Tim H. Wilson, and Ramiro Castro are GlaxoSmithKline employees. Donald J. Tindall declares that he has no relevant financial interests. Funding Information: Funding Support: This work was supported by GlaxoSmithKline . Funding Information: The authors would like to thank Roger Rittmaster, a former GlaxoSmithKline employee, for his input into the concept of the manuscript and critical review of its content. Editorial support in the form of assistance with the preparation of the first draft, collation of author comments, and preparation of tables and figures was provided by Meredith Kalish, Kate Carpenter, Helena Williams, and Kerri Bridgwater at Choice Healthcare Solutions and was funded by GlaxoSmithKline . Responsibility for opinions, conclusions and interpretation of data lies with the authors. ",
year = "2014",
month = aug,
doi = "10.1016/j.urology.2014.04.016",
language = "English",
volume = "84",
pages = "393--399",
journal = "Urology",
issn = "0090-4295",
number = "2",
}