Clinical Validation of an Epigenetic Assay to Predict Negative Histopathological Results in Repeat Prostate Biopsies

• Published in: The Journal of urology Vol. 192; no. 4; pp. 1081 - 1087
• Main Authors: Partin, Alan W, Van Neste, Leander, Klein, Eric A, Marks, Leonard S, Gee, Jason R, Troyer, Dean A, Rieger-Christ, Kimberly, Jones, J. Stephen, Magi-Galluzzi, Cristina, Mangold, Leslie A, Trock, Bruce J, Lance, Raymond S, Bigley, Joseph W, Van Criekinge, Wim, Epstein, Jonathan I
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2014
• Subjects: biopsy; Biopsy - methods; DNA Methylation; DNA, Neoplasm - genetics; Epigenesis, Genetic; epigenomics; Epigenomics - methods; Follow-Up Studies; Genes, APC; Glutathione S-Transferase pi - biosynthesis; Glutathione S-Transferase pi - genetics; Humans; Male; methylation; Polymerase Chain Reaction; Predictive Value of Tests; Prognosis; prostate; Prostate - metabolism; Prostate - pathology; prostatic neoplasms; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Tumor Suppressor Proteins - biosynthesis; Tumor Suppressor Proteins - genetics; Unnecessary Procedures - utilization; Urology; Gleason score; MATLOC; Johns Hopkins University; Methylation Analysis to Locate Occult Cancer; United States; HGPIN; PCa; NPV; University of California-Los Angeles; JHU; Detection Of Cancer Using Methylated Events in Negative Tissue; DOCUMENT; PSA; digital rectal examination; high grade prostate intraepithelial neoplasia; UCLA; epigenomics; prostate specific antigen; GS; LHMC; prostate cancer; methylation; DRE; prostatic neoplasms; biopsy; prostate; Lahey Hospital and Medical Center; U.S; negative predictive value
• ISSN: 0022-5347; 1527-3792; 1527-3792
• DOI: 10.1016/j.juro.2014.04.013

Purpose The DOCUMENT multicenter trial in the United States validated the performance of an epigenetic test as an independent predictor of prostate cancer risk to guide decision making for repeat biopsy. Confirming an increased negative predictive value could help avoid unnecessary repeat biopsies. Materials and Methods We evaluated the archived, cancer negative prostate biopsy core tissue samples of 350 subjects from a total of 5 urological centers in the United States. All subjects underwent repeat biopsy within 24 months with a negative (controls) or positive (cases) histopathological result. Centralized blinded pathology evaluation of the 2 biopsy series was performed in 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 polymerase chain reaction. Predetermined analytical marker cutoffs were used to determine assay performance. Multivariate logistic regression was used to evaluate all risk factors. Results The epigenetic assay resulted in a negative predictive value of 88% (95% CI 85–91). In multivariate models correcting for age, prostate specific antigen, digital rectal examination, first biopsy histopathological characteristics and race the test proved to be the most significant independent predictor of patient outcome (OR 2.69, 95% CI 1.60–4.51). Conclusions The DOCUMENT study validated that the epigenetic assay was a significant, independent predictor of prostate cancer detection in a repeat biopsy collected an average of 13 months after an initial negative result. Due to its 88% negative predictive value adding this epigenetic assay to other known risk factors may help decrease unnecessary repeat prostate biopsies.