Introduction

Men with persistent clinical risk factors for prostate cancer (PCa) often undergo repeat prostate biopsy for fear of occult disease missed by the first biopsy procedure. Cancer-specific DNA methylation occurs early on during the oncogenic process, and these epigenetic changes can be detected in prostate biopsy tissue at a distance from the actual tumor through a field effect. Several previously reported studies on the epigenetic assay demonstrated a negative predictive value (NPV) of 90% for all PCa and 96% for high-grade disease (Gleason Score (GS) >/=7) in men undergoing repeat prostate biopsy. We evaluated the clinical performance of this assay in a population of African American (AA) men.

Methods

The study population consisted of 237 AA men from seven urology centers across the U.S., all of whom were undergoing standard 12-core trans-rectal ultrasound guided repeat biopsy within 30 months from a negative index biopsy. Men with atypical small acinar proliferation at index biopsy were excluded. All biopsy cores were profiled for the epigenetic biomarkers GSTP1, APC and RASSF1 using a multiplexed quantitative DNA methylation-specific PCR assay.

Results

For each patient, a median of 12 cancer-negative cores from the index biopsy were analyzed. Upon repeat biopsy, 130 (55%) subjects had no PCa detected and 107 (45%) were diagnosed with PCa. Of the 107 subjects with PCa, 72 (67%) were diagnosed with GS 7 disease. Based on the expected PCa prevalence of 18% in the repeat biopsy setting, the epigenetic assay yielded an NPV of 91% and PPV of 28% for detection of all PCa. For men diagnosed with high-grade PCa, the test yielded a NPV of 96%. The epigenetic assay interrogates the DNA methylation intensity of the three cancer-related biomarkers, and higher intensities were observed for men diagnosed with high-grade PCa relative to those men with no PCa detected upon biopsy (p=0.001). _x000D_

Conclusions

In this group of AA men, we successfully validated an epigenetic assay to assess the need for repeat biopsy by profiling PCa-negative index biopsies. Results were consistent with previous studies performed on cohorts that were predominantly Caucasian. The epigenetic assay improved the identification of AA men at risk for occult high-grade disease upon repeat biopsy.

Funding

MDxHealth