Abstracts from the New England Section of the AUA 2020: A Virtual Experience

NE AUA 2020 Abstracts Scientific Session VI: Stones II/ Basic Science Methylation of SRD5A2 Promoter Predicts a Better Outcome for Patients Undergoing Androgen Deprivation Therapy in Patients with Castration Resistant Prostate Cancer Zongwei Wang, PhD 1 , Tuo Deng, MD 1 , Shulin Wu, MD 2 , Xueming Lin, MD 2 , Zhenwei Zhang, PhD 3 , Chin-Lee Wu, MD 2 , Mary-Ellen Taplin, MD 3 , Aria F. Olumi, MD 1 1 BIDMC, Boston, MA; 2 MGH, Boston, MA; 3 Dana Farber Cancer Institute, Boston, MA Introduction: Steroid 5-alpha reductase (SRD5A2) is a critical enzyme for prostatic development and growth. We have found that epigenetic modifications suppress expression of SRD5A2 in one-third of adult prostates, a condition associated with an androgenic to estrogenic switch in adult prostate tissues accounting for changes in hormonal milieu. Our objective is to demonstrate, in a well-defined subset of PCa patients, whether the SRD5A2 promoter methylation is associated with cancer progression during androgen deprivation therapy (ADT) in castration-resistant prostate cancer (CRPC). Materials &Methods: 58 CRPC samples and 36 benign prostatic specimens were studied. The methylation status of CpG site(s) at SRD5A2 promoter regions was tested via Targeted Next-Gen Bisulfite Sequencing (tNGBS). Results: Compared with benign prostatic tissue, CRPC samples demonstrated higher SRD5A2 methylation in the whole promoter region (Local CRPC cohort: P < 0.001; Met CRPC cohort: P < 0.05). Hypermethylation of specific regions (nucleotides -434 to -4 [CpG# -39 to CpG# -2]) was associated with a better overall survival (11.3 ± 5.8 vs. 6.4 ± 4.4 years, P = 0.001) and progression free survival (8.4 ± 5.4 vs. 4.5 ± 3.9 years, P = 0.003) with cutoff value of 37.9%. The protein expression of SRD5A2 was negatively correlatedwith the ratio of SRD5A2 methylation both in the whole promoter region and in the specific region. Conclusions: OurstudydemonstratesthatSRD5A2hypermethylation inspecificpromoter regions of SRD5A2, a condition that favors estrogenic as opposed to an androgenic milieu in the prostate, is significantly associated with better survival in CRPC patients who are treated with ADT. We show that a well-defined subset of prostate cancers with SRD5A2 methylation, specifically at CpG#: -39 to CpG#: -2, predicts better outcomes. Recognition of epigenetic modifications of SRD5A2, which affects the prostatic hormonal environment, may affect the choices and sequence of available therapies for management of CRPC. 62 61 Kidney Stone Volume Measurement using Ultra-Low Dose Computed Tomography and New Software Solutions Ohad Kott, MD 1 , Thomas Yi, MD 2 , Jorge Pereira, MD 3 , David Grand, MD 4 , Adib Karam, MD 4 ,DerekMerck,PhD 4 ,ScottCollins,PhD 4 ,SimoneThavaseelan,MD 5 ,GyanPareek,MD 6 . 1 Minimally Invasive Urology Institute, The MiriamHospital, Providence, RI; 2 The Warren Alpert Medical School of Brown University, Providence, RI; 3 Mount Sinai Medical Center, Miami Beach, FL; 4 Rhode Island Hospital, Providence, RI; 5 Rhode Island Hospital, Warren Alpert Medical School of Brown University, Providence, RI; 6 Minimally Invasive Urology Institute, The MiriamHospital, The Warren Alpert Medical School of Brown University, Providence, RI Introduction: Ultra-low dose computed tomography (UCT) is a promising alternative to standard dose CT (SCT) as imaging modality following nephrolithiasis treatment. Emerging software solutions allow easy stone size measurement including stone volume thatprovidesclinically important information.Thisstudyevaluated twosoftwaresolutions using UCT and SCT: Ziostation and Synapse. Materials & Methods: 29 patients with nephrolithiasis who underwent nephrolithiasis treatment between October 2017-June 2019 were imaged using SCT immediately followed by UCT. Anonymized images were randomized to an Orthanc DICOM viewer prior to a blinded review by board-certified radiologist. Max stone diameters were measured in the axial and coronal planes, using standard electronic calipers. Radiologist stone volume was modeled as ellipsoids based on the max stone diameters. Stone volumes were compared to automated measurements by Ziostation and Synapse software and compared between doses. Stone location was recorded as upper/mid/lower pole or ureter. Site specific stone burden (SSB) was calculated as cumulative stone volume in each site. Radiation exposure was calculated from CT dose reports. SSB were considered concordant if < 30 mm^3. P-value of 0.05 was used as significance cutoff. Results: 74 unique stones were identified in 29 patients. Mean exposure of UCT was significantly lower than SCT with 2.6 and 10.2 (mSv, p < 0.01) respectively. Overall radiologist measurement concordance rate was 90% between UCT and SCT, with no significant difference between doses (p = 0.91). SSB concordance rates within dose for Ziosoft and Synapse were 100% and 87% respectively. Conclusions: No statistically significant difference was detected in SSB between UCT and SCT across all exams. UCT can be used for follow-up imaging post nephrolithiasis treatment exposing the patients to less radiation. Kidney stone volume measurement of post-operativeSSBusingZiostationandSynapseisreproducibleandoperator-independent both in SCT and UCT. Adoption of such tools may benefit patients and surgeons. Dis- concordance rates in SSB between radiologist and software measurement warrant further research to determine the gold standard in SSB measurement. Genetically Defined Ancestry Reveals Unique Prostate Cancer Associated Polymorphisms in Men of African Ancestry: Analysis of the ELLIPSE Prostate Cancer Cohort Meghana S. Pagadala, BS 1 , Joshua A. Linscott, MD, PhD 2 , Hannah Carter, PhD 1 , Karim A. Kader, MD, PhD 3 , Stephen T. Ryan, MD 2 1 University of California San Diego School of Medicine, San Diego, CA; 2 Maine Medical Center, Portland, ME; 3 University of California San Diego Health, San Diego, CA Introduction: Prostatecancer(PrCa) isthesecond leadingcauseofcancerdeath inU.S.men and while PSAscreening can aid in detection, better tools are needed to stratify risk. Prior Genome-wide association studies (GWAS) using self-reported ancestry have identified PrCa associated Single Nucleotide Polymorphisms (SNPs), but the majority of these findings are specific to patients of European ancestry. We hypothesized that genetically defined ancestral groups would be a more accurate assessment of PrCa associated SNPs. Materials & Methods : Genetic, phenotype, and self-identified ethnicity (European, African American, Latino, Asian) data was obtained from the ELLIPSE Prostate Cancer Meta-Analysis and Genotyping study (a case-control study of over 99,000 men). SNPs were imputedwith theMichigan Imputation Server using the 1000 Genomes Project as the reference population. Genetic ancestry analysis was conducted using a merged identity- by-state matrix (ELLIPSE andHAPMAPstudy) and Principal ComponentAnalysis (PCA). A k-means clustering model trained on HAPMAP data was used to determine that the ELLIPSE cohort best fit with 5 ancestral groups from the HAPMAP data: European n = 82551,African n = 6355, Mexican n = 1925, Indian n = 522 andAsian n = 291. Self-identified andgenetically definedancestralgroups werecomparedwithPCA.Genome-wide analysis were performed and SNPs passing the p-threshold of 5x10 -8 were analyzed. Results : Genetically defined ancestral groups better controlled for effects of population stratification than self-identified ancestral groups (p < 3.47x10 -9, Figure 1). European and African ancestral groups were well-powered for analysis with numerous SNPs passing the p-threshold. Manhattan plot of the African ancestral group showed significant associations on chromosome 8, with multiple SNPs aligning with described loci in European populations. Unique SNPs were noted on chromosomes 6 and 11 (Figure 2). The Mexican, Indian and Asian ancestral groups were not sufficiently powered for analyses. Conclusions : Patients in the ELLIPSE cohort have significantly better grouping when stratified by genetic ancestry compared to self-identified ancestry. Specifically, the cohort can be sorted into 5 ancestral groups that align with groups described by the International HAPMAP Project. Furthermore, GWAS using genetically identified ancestry uncovered SNPs specific to minority ethnic groups. Future characterization of these PrCa risk SNPs could aid individualized screening recommendations within the African American population. 60 27