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J Urol. 2014 Oct;192(4):1081-7. doi: 10.1016/j.juro.2014.04.013. Epub 2014 Apr 18.

Clinical validation of an epigenetic assay to predict negative histopathological results in repeat prostate biopsies.

Author information

1
James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland. Electronic address: apartin@jhmi.edu.
2
Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, The Netherlands; MDxHealth, Inc., Irvine, California.
3
Glickman Urological Institute, Cleveland Clinic, Cleveland, Ohio.
4
Department of Urology, University of California-Los Angeles, Los Angeles, California.
5
Lahey Hospital and Medical Center, Burlington, Massachusetts.
6
Leroy T. Canoles Jr. Cancer Research Center, East Virginia Medical School, Norfolk, Virginia.
7
James Buchanan Brady Urological Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland.
8
MDxHealth, Inc., Irvine, California.
9
MDxHealth, Inc., Irvine, California; Laboratory of Bioinformatics and Computational Genomics, Ghent University, Ghent, Belgium. Electronic address: wim.vancriekinge@mdxhealth.com.

Abstract

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.

KEYWORDS:

biopsy; epigenomics; methylation; prostate; prostatic neoplasms

PMID:
24747657
PMCID:
PMC4337855
DOI:
10.1016/j.juro.2014.04.013
[Indexed for MEDLINE]
Free PMC Article

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