Abstract 2390: Clinical validation of an epigenetic field of susceptibility to detect significant prostate cancer from 2 non-tumor biopsies

Background: An epigenetic field of cancer susceptibility exists for prostate cancer that gives rise to multifocal disease in the peripheral zone. In a previous studies (Neoplasia 2013, J Urol 2014) we identified using methylation arrays over 50 altered regions in normal prostate tissue of men with prostate cancer. In the current multicenter study, a validation was performed to determine the predictive strength of this approach. Methods: We evaluated 2 archived, cancer negative prostate biopsy core tissue from 129 subjects from 4 urological centers. All negative cases (controls) underwent 2 or more repeat negative biopsies within 24 mo with a central review of all histopathology. Cancer cases were negative biopsies selected from patients who ultimately went prostate removal to confirm a final grade >Gleason Score 7. Biopsies were analyzed using pyrosequencing for DNA methylation changes at multiple CpGs surrounding the genes EVX1, CAV1, PLA2G16, FGF1, SPAG4 and NCR2. Analyses used multiplex logistic regression modeling with backward elimination. Results: Patients diagnosed with GS>7 cancer (77) and the control group (52) were similarly matched except for PSA (7 vs 5.8; p 7 prostate cancers (AUC 0.808, p=0.001). Conclusions: A widespread epigenetic field defect can be used to detect GS>7 prostate cancers in patients with histologically negative biopsies. This assay is sensitive in requiring only 2 biopsies and detects alterations in nontumor cells at distance from the cancer. This has the potential to decrease the need for repeat prostate biopsies, a procedure associated with cost and complications. Support: UW Ignitor; Gen X foundation Citation Format: Bing Yang, Johnathon McCormick, Adam Schultz, Glen Leverson, Geoffrey Sonn, Cristina Magi-Galluzi, Eric A. Klein, Michael Fumo, David F. Jarrard. Clinical validation of an epigenetic field of susceptibility to detect significant prostate cancer from 2 non-tumor biopsies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2390. doi:10.1158/1538-7445.AM2017-2390