Combined Dna-Methylation Intensity And Clinical Risk Score To Stratify Patients For High-Grade Disease.

51 Background: Prostate cancer (PCa) diagnostics remains challenging due to fear of over-diagnosis and overtreatment. Due to low accuracy of PSA too many men are biopsied that do not have a subsequent PCa diagnosis or that have indolent disease. Furthermore, persistent risk factors and fear of missed PCa leads to many unnecessary repeat biopsies. Most prostate tumors have epigenetic DNA-methylation aberrations, which display a field effect that can be observed in normal-appearing surrounding tissue, and that could help alleviate biopsy-sampling errors. Methods: A training cohort of methylation-positive men with a negative index biopsy followed by either a Gleason score (GS) ≥ 7 (n=43) or cancer-negative (n=226) repeat biopsy was evaluated. Using the initial negative biopsy, men were stratified for the likelihood of harboring high-grade PCa focusing on a methylation intensity algorithm involving GSTP1, RASSF1 and APC. This algorithm was validated in a cohort of 102 men, with either a PCa-free (n=20), GS6 (...