MP33-10 EVALUATION OF THE CLINICAL UTILITY OF AN EPIGENETIC ASSAY TO REDUCE UNNECESSARY REPEAT PROSTATE BIOPSIES Leander Van Neste, Maastricht, Netherlands; Jack Groskopf, Irvine, CA; Wim Van Crienke*, Ghent, Belgium INTRODUCTION AND OBJECTIVES: Background: Manage- ment of men at risk of prostate cancer (PCa), but with a cancer-negative index biopsy, remains a challenge. PCa diagnosis involves an invasive biopsy procedure that is subject to significant sampling errors, possible negative quality-of-life implications for the patient and high additional costs to the healthcare system. An epigenetic assay assessing PCa- associated DNA-methylation of GSTP1, RASSF1, and APC in histo- logically negative biopsies has previously been clinically validated to improve the negative predictive value (NPV) relative to standard of care (SOC), yielding a NPV of 90% for all PCa and 96% for high-grade PCa (Gleason Score 7 or higher). Examination of the repeat biopsy rate associated with the outcome of this epigenetic assay would provide further evidence of its clinical utility for improving urologists’ manage- ment of previously biopsied patients. Objective:The primary goal of this study was to determine the rate of repeat biopsy in relation to the epigenetic assay and how this impacted the management of patients. METHODS: Practicing urologists used the epigenetic assay to evaluate 986 men (680 in the case group and 306 in the control group) with a previous negative biopsy. Men in the Case group had an epigenetic assay-negative result and were prospectively followed for a minimum of 12 months from the date of epigenetic profiling. The Control group was managed under SOC. RESULTS: The two groups were balanced in terms of patient characteristics, except for median age, which was lower in the Case group compared to the Control group (62 vs. 66 years, p<0.001). Use of the epigenetic assay resulted in significantly fewer first repeat biopsies in the Case group compared to the Control group (7.8% vs. 15.4%, respectively; p¼0.004). There were also significantly fewer second repeat biopsies in the Case group compared to the Control group (12.1% vs. 26.1%, respectively; p<0.001) and significantly lower PCa detection upon repeat biopsy after a negative epigenetic assay result in the Case group compared to the Control group (0.6% vs. 4.9%, respectively; p<0.001). CONCLUSIONS: In this real-world prospective study, the use of the epigenetic assay resulted in a significant reduction in the rate of excess repeat prostate biopsies. Source of Funding: MDxHealth, Inc. MP33-11 GENETIC RISK SCORE CAN DISTINGUISH RISK OF PROSTATE CANCER AMONG FAMILY MEMBERS WITH SIMILAR DEGREES OF RELATIONSHIP Brian Helfand*, Evanston, IL; Haitao Chen, Rong Na, Shanghai, China, People’s Republic of; Carly Conran, Evanston, IL; William Catalona, Chicago, IL; Jianfeng Xu, Evanston, IL INTRODUCTION AND OBJECTIVES: Family history is a well- established risk factor for prostate cancer (PCa). However, family his- tory information assigns equivalent risk to all relatives based upon the degree of relationship. Recent genetic studies have identified single nucleotide polymorphisms (SNPs) that can be used to calculate a ge- netic risk score (GRS) to determine an individual 0 s PCa risk. We sought to determine whether GRS can better estimate PCa risk among in- dividuals with a family history of PCa. METHODS: Patients evaluated at a tertiary referral clinic with a family history of PCa were recruited for this study and were genotyped for 26 SNPs previously associated with PCa. The degree of familial risk (F) was calculated for each subject based on PCa among his relatives (e.g. F value of 0.5¼ 1 first-degree relative with PCa or 2 second-degree relatives with PCa). A GRS value was also calculated for each subject using 26 SNPs. Analyses comparing the distribution of GRS values among affected and unaffected family members with varying F values were performed. RESULTS: Subjects from 811 families with at least two affected members were included. The median GRS was significantly higher among family members with PCa (median 1.31; range 0.21-11.64) compared to unaffected family members (median 1.03; range 0.18-6.32; p¼9.69e-8). There was a wide distribution of GRS values among members of each F group (Table). Higher GRS values were significantly associated with increased PCa risk among all F groups (p<0.05). For example, among subjects with F values of 1-1.49, PCa patients had a high mean GRS (1.64) than non-PCa subjects (1.12), P¼0.0015. Multivariate models to assess the associations between age, GRS, F value and PCa diagnosis demonstrate that higher GRS (P¼1.36e-7) and higher F values (P¼2.64e-9) were independently associated with increased PCa risk. CONCLUSIONS: GRS is an objective measurement that allows for differentiation of PCa risk among family members with similar de- grees of familial risk of PCa. While prospective validation studies are required, this information can help guide relatives in regards to the time of initiation and frequency of PCa screening. Source of Funding: none MP33-12 DEVELOPMENT OF A PROSTATE CANCER GENE EXPRESSION PANEL TO ADDRESS RACIAL DIFFERENCES OF MOLECULAR ALTERATIONS IN PROSTATE CANCER Indu Kohaar*, Lakshmi Ravindranath, Sreedatta Banerjee, Yongmei Chen, Amina Ali, Rockville, MD; Jacob Kagan, Sudhir Srivastava, Bethesda, MD; Albert Dobi, David McLeod, Rockville, MD; Inger Rosner, Bethesda, MD; Shiv Srivastava, Gyorgy Petrovics, Rockville, MD INTRODUCTION AND OBJECTIVES: Prostate cancer (CaP) affects 1 in 7 men in their life time. One of the major risk factors for the development of CaP is race/ethnicity. African American (AA) men have significantly higher incidence and mortality from CaP compared to Caucasian American (CA) men. Emerging data including ours have described significantly lower frequencies of alterations in common CaP driver genes (ERG and PTEN) in AA men as compared to CA men. We have also noted that genes commonly overexpressed in CaP (ERG, AMACR, PCA3), and currently used as diagnostic markers, exhibit much lower frequency and more heterogeneity in AA men. The goal of this study was to define a CaP marker panel that is overexpressed equally well in AA and CA CaP. METHODS: Three platforms (RNASeq, NanoString and qRT- PCR) were used for evaluation of CaP associated gene expression in CA and AA patients (N¼144). Candidate genes with robust tumor overexpression (over 4-fold) in CaP in paired normal and tumor speci- mens from AA and CA patients were selected from Nanostring and RNASeq data for validation by qRT-PCR (TaqMan) in laser micro- dissected (LCM) tumor and benign cells of frozen tissue sections (50 Vol. 197, No. 4S, Supplement, Saturday, May 13, 2017 THE JOURNAL OF UROLOGY â e421