Predicting Prostate Biopsy Result in Men With Prostate Specific Antigen 2.0 to 10.0 ng/ml Using an Investigational Prostate Cancer Methylation Assay

Purpose: The inadequacies of prostate specific antigen testing have created a need for novel markers for prostate cancer screening. The investigational ProCaM (TM) prostate cancer methylation assay detects aberrant methylation of DNA in cells associated with prostate cancer. We describe a large, prospective, multicenter study done to verify the performance of this assay. Materials and Methods: The assay is designed to detect epigenetic modifications in the 3 markers GSTP1, RAR beta 2 and APC, which are indicative of prostate cancer. A total of 232 men with cancer and 283 without cancer from 18 clinical sites were evaluated by trained operators at central testing laboratories. Study inclusion criteria were age 40 to 75 years, total prostate specific antigen between 2.0 and 10.0 ng/ml, and a digital rectal examination result. All participants signed an informed consent form and underwent transrectal ultrasound guided needle biopsy with 10 or more cores. Results: Assay sensitivity was 60%, specificity was 80% and the informative rate was 97%. Assay predictive accuracy was higher than that of age, digital rectal examination, family history, prostate specific antigen, prior negative biopsy and prostate volume (AUC 0.73 vs 0.52 to 0.66, p < 0.038). Risk factors plus the assay improved overall predictive power (AUC 0.79, p = 0.001). A man with a positive prostate cancer methylation result was 7.7 times more likely to have high grade cancer. Conclusions: The prostate cancer methylation assay correlated with positive biopsy and with Gleason score. This assay has the potential to add value to the biopsy decision making process by improving current prostate cancer screening algorithms to more accurately identify men with prostate cancer.