A New Test May Change the Meaning of a “Negative” Prostate Biopsy

Nearly one million men undergo prostate biopsy yearly in the US. 750,000 (3 in 4) of these biopsies are histologically found to be negative for evidence of prostate cancer by microscopic analysis. Other data suggest that of these 750,000 negative biopsies, 25% (187,000) actually have cancer in the prostate that the initial biopsy might have missed. A new tissue assay (made by ConfirmMDx) 

From MDxHealth.com

looks at the methylation (alteration of the DNA) of three genes to predict that cancer may have been missed and that a repeat biopsy should be recommended. The test relies on the concept that a "halo" of DNA-alterations (methylation) occurs around a foci of cancer within the prostate. With the ability to search for DNA-abnormalities in the "halo," this test effectively increases the size of each biopsy and decreases the likelihood of missing a prostate cancer.

Jonathan I. Epstein, MD

The multicenter DOCUMENT (Detection of Cancer Using Methylated Events in Negative Tissue) study was conducted with 350 PSA-screened men from five major urologic centers, including Johns Hopkins University, Cleveland Clinic Foundation, Lahey Clinic, University of California Los Angeles and East Virginia Medical School. The study involved patients with an initial negative index prostate biopsy who had high-risk variables (e.g. High Grade PIN, Atypia high PSA, etc…) and compared this tissue methylation assay results to cancer detection in subsequent repeat biopsy within 24 months. Index and repeat biopsy tissues were subjected to blinded, centralized pathology review by Jonathan Epstein, MD, Reinhard Professor of Urologic Pathology and Director of Surgical Pathology at Johns Hopkins. The ConfirmMDx for Prostate Cancer test, was used to analyze the DNA from 3,687 negative tissue cores from the index prostate biopsy for epigenetic abnormalities. The study confirmed the previously published results using the same ConfirmMDx for Prostate Cancer test as a significant, independent predictor (odds ratio = 2.85) for the risk of prostate cancer in a repeat biopsy, outperforming standard clinical risk factors such as age, prostate specific antigen (PSA), digital rectal exam (DRE), and pathology in multivariate logistic regression analysis. In addition, the high negative predictive value of the epigenetic assay was confirmed (88%).[1]

Alan W. Partin, MD, PhD

Dr. Alan Partin, MD, PhD, Chairman of the Brady Urological Institute and Urologist-in-Chief at Johns Hopkins Hospital comments, 

"The DOCUMENT study validates the three-gene epigenetic assay as a better predictor of risk for the presence of occult cancer than any other factor in the clinic today. Results from this study provide further clinical evidence that the epigenetic test delivers actionable information to help guide urologists on the decision for repeat prostate biopsy."

"DOCUMENT was a pivotal validation study, demonstrating that the test's high negative predictive value and odds ratio are robust and reproducible in different cohorts of patients," stated Dr. Epstein. "The importance of this blinded, multicentered study is that it validated the performance of the test using predetermined analytical cutoff values in a population of U.S. patients undergoing routine PSA screening for prostate cancer."

The entire manuscript appears in the April 18, 2014 Edition of the Journal of Urology. Click here of follow the link below to read the entire manuscript.

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. Clinical Validation of an Epigenetic Assay to Predict Negative Histopathological Results in Repeat Prostate Biopsies. J Urol. 2014 Apr 18. pii: S0022-5347(14)03341-2. doi: 10.1016/j.juro.2014.04.013.


 
[1] Stewart GD, Van Neste L, Delvenne P, Delrée P, Delga A, McNeill SA, O'Donnell M, Clark J, Van Criekinge W, Bigley J, Harrison DJ. Clinical utility of an epigenetic assay to detect occult prostate cancer in histopathologically negative biopsies: results of the MATLOC study. J Urol. 2013 Mar;189(3):1110-6. doi: 10.1016/j.juro.2012.08.219. Epub 2012 Oct 8.