MP63-14 MULTICENTER VALIDATION STUDY OF A TISSUE METHYLATION ASSAY TO PREDICT HISTOPATHOLOGICALLY CANCER-NEGATIVE REPEAT PROSTATE BIOPSIES

Abstract

You have accessJournal of UrologyProstate Cancer: Detection & Screening III1 Apr 2014MP63-14 MULTICENTER VALIDATION STUDY OF A TISSUE METHYLATION ASSAY TO PREDICT HISTOPATHOLOGICALLY CANCER-NEGATIVE REPEAT PROSTATE BIOPSIES Alan Partin, Eric Klein, Leonard Marks, Jason Gee, Dean Troyer, Leslie Mangold, Kimberly Christ, Joseph Bigley, Leander Van Neste, and Jonathan Epstein Alan PartinAlan Partin More articles by this author , Eric KleinEric Klein More articles by this author , Leonard MarksLeonard Marks More articles by this author , Jason GeeJason Gee More articles by this author , Dean TroyerDean Troyer More articles by this author , Leslie MangoldLeslie Mangold More articles by this author , Kimberly ChristKimberly Christ More articles by this author , Joseph BigleyJoseph Bigley More articles by this author , Leander Van NesteLeander Van Neste More articles by this author , and Jonathan EpsteinJonathan Epstein More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.1951AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A negative initial prostate biopsy in conjunction with persistent risk factors, such as increased PSA, often lead to rebiopsy. A multicentered US trial was performed among PSA-screened men to validate a multiplex epigenetic assay used to detect DNA-methylation events in histopathologically negative for cancer initial prostate biopsies. The epigenetic assay complements the pathologic review resulting in a higher negative predictive value (NPV). The assay provides additional molecular information, based on cancer-associated epigenetic changes, to avoid unnecessary repeat prostate biopsies METHODS The DOCUMENT (Detection of Cancer Using Methylated Events in Negative Tissue) study evaluated 3687 histopathologically-negative biopsy core samples from 350 men from 5 urologic centers. All subjects had a repeat biopsy within 24 months with a positive (cases) or negative (controls) histopathological result. All cores from the initial and repeat biopsies were subjected to blinded centralized pathology (J.E.). Patients with ASAP in the first biopsy were excluded, however HGPIN was accepted. Gene markers GSTP1, APC and RASSF1 were tested with a multiplexed methylation-specific PCR (MSP) assay to validate the results from the European MATLOC study. The cancer prevalence rate of the DOCUMENT cohort was adjusted to 18% to allow direct comparison. The predetermined analytical gene marker cutoffs from MATLOC were used to demonstrate clinical performance. RESULTS The epigenetic assay resulted in an NPV of 88% (95% confidence interval (CI), 85-91%), a sensitivity of 60% (95% CI, 50-71%) and specificity of 64% (95% CI, 57-70%). Detection of cancer-associated DNA-methylation in the first biopsy was associated with an odds ratio of 2.33 (95% CI, 1.27-4.01; p = 0.004) when corrected for other risk factors such as histopathology (p=0.040), age (p=0.046), PSA (p=0.254) and race (p=0.758). CONCLUSIONS The DOCUMENT study validates this epigenetic assay as a significant, independent predictor for the absence of prostate cancer in a repeat biopsy in this US population. These findings are consistent with and confirm the results from the earlier European MATLOC study, demonstrating an NPV of 90% (95% CI, 86-94%). The consistently high NPV of the epigenetic assay is significantly higher than the use of standard histopathology alone. The addition of this test to other commonly known risk factors can be used to reduce unnecessary repeat prostate biopsies. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e713-e714 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Alan Partin More articles by this author Eric Klein More articles by this author Leonard Marks More articles by this author Jason Gee More articles by this author Dean Troyer More articles by this author Leslie Mangold More articles by this author Kimberly Christ More articles by this author Joseph Bigley More articles by this author Leander Van Neste More articles by this author Jonathan Epstein More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...