Estimating rates of true high-grade disease in the prostate cancer prevention trial.

The Prostate Cancer Prevention Trial (PCPT) showed a decreased prostate cancer rate but an increased rate of high Gleason grade disease on biopsy for finasteride versus placebo. The results from radical prostatectomy (RP) on 25% of the men undergoing RP have recently been reported and suggest that grading artifacts in biopsy Gleason scoring may have occurred. We used a statistical model to extrapolate the RP Gleason results to all men in the PCPT using a missing-at-random assumption. We estimated the rates of true high-grade (Gleason 7-10) and true low-grade disease, where true Gleason grade is what is (or would have been) found on RP. We also estimated misclassification rates on biopsy of true high-grade and low-grade disease. We show that the rate of upgrading of biopsy low-grade disease to high-grade on RP is a function of misclassification rates as well as the ratio of true low-grade to high-grade disease. The estimated relative risks for true low-grade and true high-grade disease for finasteride compared with placebo were 0.61 (95% confidence interval, 0.51-0.71) and 0.84 (95% confidence interval, 0.68-1.05), respectively. The misclassification rate of true high-grade disease (to low-grade disease on biopsy) was significantly lower for finasteride (34.6%) than for placebo (52.6%). Although misclassification rates differed, upgrading rates were similar in each arm due to the different ratios of true low-grade to high-grade disease in each arm. Results from RP show that misclassification rates on biopsy were higher in the placebo arm and that the rate of true high-grade disease may have been lower in the finasteride arm.