title: Estimating rates of true high-grade disease in the prostate cancer prevention trial.
abstract: 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.
authors.affiliation: Division of Cancer Prevention, National Cancer Institute, 6130 Executive Boulevard, EPN 3064, Bethesda, MD 20892, USA. pp4f@nih.gov
authors.forename: Paul
authors.initials: P
authors.lastname: Pinsky
authors.forename: Howard
authors.initials: H
authors.lastname: Parnes
authors.forename: Leslie
authors.initials: L
authors.lastname: Ford
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001706:Biopsy; D018450:Disease Progression; D005189:False Positive Reactions; D018120:Finasteride / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010919:Placebos; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology* / Q000517:prevention & control
chemical_list: D000970:Antineoplastic Agents; D010919:Placebos; D018120:Finasteride