Epigenetic risk score improves prostate cancer risk assessment

BackgroundEarly detection of aggressive prostate cancer (PCa) remains crucial for effective treatment of patients. However, PCa screening remains controversial due to a high rate of overdiagnosis and overtreatment. To better reconcile both objectives, more effective methods for assessing disease severity at the time of diagnosis are needed.MethodsThe relationship between DNA-methylation and high-grade PCa was examined in a cohort of 102 prospectively enrolled men who received standard 12-core prostate biopsies. EpiScore, an algorithm that quantifies the relative DNA methylation intensities of GSTP1, RASSF1, and APC in prostate biopsy tissue, was evaluated as a method to compensate for biopsy under-sampling and improve risk stratification at the time of diagnosis.ResultsDNA-methylation intensities of GSTP1, RASSF1, and APC were higher in biopsy cores from men diagnosed with GS7 cancer compared to men with diagnosed GS 6 disease. This was confirmed by EpiScore, which was significantly higher for subjects with high-grade biopsies and higher NCCN risk categories (both PConclusionsIn men diagnosed with PCa, DNA-methylation profiling can detect under-sampled high-risk PCa in prostate biopsy specimens through a field effect. Predictive accuracy increased when EpiScore was combined with other clinical risk factors. These results suggest that EpiScore could aid in the detection of occult high-grade disease at the time of diagnosis, thereby improving the selection of candidates for Active Surveillance.