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

Area of Science:

• Urology
• Oncology
• Clinical Trials

Background:

• The Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial observed a numerical imbalance in Gleason 8-10 prostate cancers (PCa) between dutasteride and placebo groups in years 3-4.
• Investigating the reasons for this imbalance is crucial for understanding dutasteride's potential effects on aggressive PCa detection.

Purpose of the Study:

• To explore explanations for the observed numerical imbalance of biopsy-detected Gleason 8-10 PCa in years 3-4 of the REDUCE study.
• To evaluate the impact of baseline predictors and prostate volume on PCa diagnosis within the trial.

Main Methods:

• Analysis of data from the 4-year, randomized, double-blind, placebo-controlled REDUCE trial.
• Modeling of Gleason 8-10 PCa incidence and logistic regression analysis.
• Comparison of needle biopsy Gleason scores with corresponding prostatectomy Gleason scores.

Main Results:

• Simulated year 4 biopsy scheduling estimated similar Gleason 8-10 PCa incidence (45 dutasteride vs. 46 placebo).
• Two Gleason 7 cancers in the placebo group were upgraded to Gleason 8-10 upon prostatectomy, versus none in the dutasteride group.
• Logistic regression identified prostate volume at biopsy as a significant factor influencing Gleason 8-10 PCa diagnosis.

Conclusions:

• While year 4 modeling suggests similar underlying incidence, an association between dutasteride and Gleason 8-10 PCa cannot be definitively ruled out.
• Study design biases and prostate size at biopsy likely contributed to the observed numerical imbalance in high-grade PCa detection between years 3-4.