A Urine-Based Dna Methylation Marker Test To Detect Upper Tract Urothelial Carcinoma: A Pilot Study

You have accessJournal of UrologyBladder Cancer: Upper Tract Transitional Cell Carcinoma I (PD43)1 Sep 2021PD43-04 A URINE-BASED DNA METHYLATION MARKER TEST TO DETECT UPPER TRACT UROTHELIAL CARCINOMA: A PILOT STUDY Alireza Ghoreifi, Sanam Ladi-Seyedian, Paolo Piatti, Benjamin Jara, Taikun Yamada, Lucy Sanossian, Sina Sobhani, Andrew Hung, Sumeet Bhanvadia, Rene Sotelo, Monish Aron, Mihir Desai, Inderbir Gill, Siamak Daneshmand, Gangning Liang, and Hooman Djaladat Alireza GhoreifiAlireza Ghoreifi More articles by this author , Sanam Ladi-SeyedianSanam Ladi-Seyedian More articles by this author , Paolo PiattiPaolo Piatti More articles by this author , Benjamin JaraBenjamin Jara More articles by this author , Taikun YamadaTaikun Yamada More articles by this author , Lucy SanossianLucy Sanossian More articles by this author , Sina SobhaniSina Sobhani More articles by this author , Andrew HungAndrew Hung More articles by this author , Sumeet BhanvadiaSumeet Bhanvadia More articles by this author , Rene SoteloRene Sotelo More articles by this author , Monish AronMonish Aron More articles by this author , Mihir DesaiMihir Desai More articles by this author , Inderbir GillInderbir Gill More articles by this author , Siamak DaneshmandSiamak Daneshmand More articles by this author , Gangning LiangGangning Liang More articles by this author , and Hooman DjaladatHooman Djaladat More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002057.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Upper tract urothelial carcinoma (UTUC) is an uncommon, yet lethal tumor of the urinary tract. Diagnosis and preoperative risk stratification of these patients present distinct challenges given the limitations of current available diagnostic tools, including endoscopic biopsy and imaging. Herein, we explore the feasibility of a urine-based epigenetic assay to detect UTUC. METHODS: Under an IRB approved protocol, urine samples were collected from UTUC patients before radical nephroureterectomy between December 2019 and December 2020. Patients with concomitant bladder cancer (n=4) and those who did not pass the quality control due to low DNA concentration (n=5) were excluded. Samples were analyzed with Bladder CARE™, a urine-based assay that measures methylation levels of 3 cancer biomarkers (TRNA-Cys, SIM2, and NKX1-1) and two internal control loci using methylation-sensitive restriction enzymes coupled with qPCR. Results are reported as Bladder CARE Index (BCI) score and categorized as positive (BCI>5), high-risk (BCI 2.5-5), or negative (BCI<2.5), which correlate to the concentration of cancer DNA in the sample. The findings were compared to 54 sex/age matched healthy (cancer-free) individuals. RESULTS: A total of 19 patients with a median age of 73 (14 male and 5 female) were included in the final analysis. Separate samples were sent from bladder and nephrostomy tube in 2 patients (total urine sample n=21). Final pathology revealed stage Ta (n=11), T1 (n=2), T2 (n=2), and T3 (n=4) UTUC. Among all samples, 20 showed positive and 1 high-risk BCI results. Urine cytology was available in 9 patients, in whom 3 had positive BCI results despite negative cytology. UTUC patients had a significantly higher BCI values compared to the control cases (average BCI value of 227.3 vs. 1.7, respectively; p < 0.0001) (Figure 1-A). The Receiver Operating Characteristic (ROC) curve demonstrating the sensitivity, specificity, positive predictive values, and negative predictive value of 100%, 87.1%, 75%, and 100%, respectively (AUC=0.996, Fig. 1B). CONCLUSIONS: In this pilot study, the proposed urine-based epigenetic assay showed high sensitivity and negative predictive value in the diagnosis of patients with UTUC. A larger sample size study to validate the accuracy of this test is the next step. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e731-e732 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Alireza Ghoreifi More articles by this author Sanam Ladi-Seyedian More articles by this author Paolo Piatti More articles by this author Benjamin Jara More articles by this author Taikun Yamada More articles by this author Lucy Sanossian More articles by this author Sina Sobhani More articles by this author Andrew Hung More articles by this author Sumeet Bhanvadia More articles by this author Rene Sotelo More articles by this author Monish Aron More articles by this author Mihir Desai More articles by this author Inderbir Gill More articles by this author Siamak Daneshmand More articles by this author Gangning Liang More articles by this author Hooman Djaladat More articles by this author Expand All Advertisement Loading ...