Ability of an epigenetic assay to identify anterior prostate tumors based on a negative 12-core biopsy.

Abstract

131 Background: There is increasing awareness that anterior-predominant prostate cancers (PCa) are poorly sampled by 12-core transrectal ultrasound-guided (TRUS) prostate biopsies. Approximately one-fifth of all prostate tumors occur in this area, and many are high grade and extend beyond the prostatic capsule. An epigenetic assay, detecting PCa-specific DNA-methylation of GSTP1, RASSF1 and APC has shown to be a significant predictor for the presence of PCa in histopathologically cancer-negative biopsies through a cancer-associated field effect. It is currently unknown whether the field effect from an anterior-predominant cancer may be detected in standard posteriorly-directed sextant biopsy specimens. Methods: Seven patients with at least one prior negative TRUS biopsy were subsequently diagnosed with anterior-only PCa based on a transperineal mapping template prostate biopsy (MTPB). Three patients were diagnosed with low-grade Gleason score (GS) 6 tumors and four patients with GS ≥7 tumors. The outcome of the MTPB was compared with the result of the epigenetic test performed on the prior cancer-negative TRUS biopsy. Results: MTPB included a median of 68 cores (IQR 53-76). A total of 6 patients (86%) were methylation-positive at initial biopsy, suggesting that the field effect from these anterior-predominant cancers extends to the region of TRUS biopsy sampling. No methylation was found for one patient with only one GS6 positive core at MTPB and a tumor volume of 4%. Methylation intensities were higher for patients with GS ≥7 compared to those with GS6. A logistic regression model combining these intensities with traditional risk factors (PSA, age, TRUS-biopsy pathology and DRE) indicated higher risk scores for high-grade tumors. Conclusions: Aberrant DNA-methylation patterns are present in normal-appearing tissue from TRUS biopsy of patients with anteriorly located tumors. Although a small study, this is a unique cohort that underwent extensive sampling at re-biopsy demonstrating the presence of an anterior-predominant tumor. These results indicate that an epigenetic assay may be valuable even in patients with negative posteriorly-directed TRUS biopsies to detected anterior-predominant PCa.