PURPOSE: The Detection Of Cancer Using Methylated Events in Negative Tissue (DOCUMENT) U.S. multicenter trial validated the performance of an epigenetic test as independent predictor of prostate cancer (PCa) risk to guide decision for repeat biopsy.
Confirming an increased negative predictive value (NPV) could help avoid unnecessary repeat biopsies.
MATERIALS AND METHODS: Archived negative-for-cancer prostate biopsy core tissue samples of 350 subjects from five urologic centers in the U.S. were evaluated. All subjects underwent a repeat biopsy within 24 months with a negative (controls) or positive (cases) histopathological result. Centralized, blinded pathology on both biopsy series was performed on all available subjects from each site. Biopsies were epigenetically profiled for GSTP1, APC and RASSF1 relative to the ACTB reference gene using quantitative methylation-specific PCR. Predetermined analytical marker cutoffs were used to demonstrate assay performance. Multivariate logistic regression was used to evaluate all risk factors.
RESULTS: The epigenetic assay resulted in a NPV of 88% (95% CI, 85-91%). In multivariate models, correcting for age, PSA, DRE, histopathological characteristics of the first biopsy and race, the test proved to be the most significant, independent predictor of patient outcome with an odds ratio of 2.69 (95% CI: 1.60 - 4.51).
CONCLUSIONS: The DOCUMENT study validates that the epigenetic assay is a significant, independent predictor of PCa detection in a repeat biopsy collected, on average, thirteen months after an initial negative result. With a NPV of 88%, the addition of this epigenetic assay to other known risk factors may help reduce unnecessary repeat prostate biopsies.
Partin AW, Van Neste L, Klein EA, Marks LS, Gee JR, Troyer DA, Rieger-Christ K, Jones JS, Magi-Galluzzi C, Mangold LA, Trock BJ, Lance RS, Bigley JW, Van Criekinge W, Epstein JI. Are you the author?
James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA; Department of Pathology, GROW, Maastricht University Medical Center, Maastricht, The Netherlands; Glickman Urological Institute, Cleveland Clinic, Cleveland, OH, USA; UCLA Department of Urology, Los Angeles, CA, USA; Lahey Hospital & Medical Center, Burlington, MA, USA; Leroy T. Canoles Jr. Cancer Research Center, East Virginia Medical School, Norfolk, VA, USA; MDxHealth Inc, Irvine, CA, USA; Laboratory of Bioinformatics and Computational Genomics, Ghent University, Belgium. ;
Reference: J Urol. 2014 Apr 16. pii: S0022-5347(14)03341-2.