MP22-19 URINARY COMPREHENSIVE GENOMIC PROFILING PREDICTS UROTHELIAL CANCER UP TO 12 YEARS AHEAD OF CLINICAL DIAGNOSIS. AN EXPANDED ANALYSIS OF THE GOLESTAN COHORT STUDY (2023)

You have accessJournal of UrologyCME1 Apr 2023MP22-19 URINARY COMPREHENSIVE GENOMIC PROFILING PREDICTS UROTHELIAL CANCER UP TO 12 YEARS AHEAD OF CLINICAL DIAGNOSIS. AN EXPANDED ANALYSIS OF THE GOLESTAN COHORT STUDY Yair Lotan, Keyan Salari, Adam Feldman, Debasish Sundi, Jason J Lee, Gabrielle DiFiore, Hossein Poustchi, Masoud Khoshnia, Gholamreza Roshandel, Arash Etemadi, Mahdi Goudarzi, Peter S. Lentz, Kevin G. Phillips, Vincent T. Bicocca, Theresa M. Koppie, Joe W. Gray, Trevor Levin, Reza Malekzadeh, Mahdi Sheikh, and Florence Le Calvez-Kelm Yair LotanYair Lotan More articles by this author , Keyan SalariKeyan Salari More articles by this author , Adam FeldmanAdam Feldman More articles by this author , Debasish SundiDebasish Sundi More articles by this author , Jason J LeeJason J Lee More articles by this author , Gabrielle DiFioreGabrielle DiFiore More articles by this author , Hossein PoustchiHossein Poustchi More articles by this author , Masoud KhoshniaMasoud Khoshnia More articles by this author , Gholamreza RoshandelGholamreza Roshandel More articles by this author , Arash EtemadiArash Etemadi More articles by this author , Mahdi GoudarziMahdi Goudarzi More articles by this author , Peter S. LentzPeter S. Lentz More articles by this author , Kevin G. PhillipsKevin G. Phillips More articles by this author , Vincent T. BicoccaVincent T. Bicocca More articles by this author , Theresa M. KoppieTheresa M. Koppie More articles by this author , Joe W. GrayJoe W. Gray More articles by this author , Trevor LevinTrevor Levin More articles by this author , Reza MalekzadehReza Malekzadeh More articles by this author , Mahdi SheikhMahdi Sheikh More articles by this author , and Florence Le Calvez-KelmFlorence Le Calvez-Kelm More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003247.19AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Detecting pre-clinical urothelial carcinoma (UC) using urinary comprehensive genomic profiling (uCGP) may provide a valuable opportunity for early detection and screening of high-risk populations. The UroAmp (Convergent Genomics) uCGP test uses DNA sequencing to identify mutations across 60 genes. We study a subset of these genes, considering 10 genes with the highest performance, testing the potential of a screening modified uCGP (muCGP) to detect preclinical UC. METHODS: A UC screening model was developed using muCGP data from a training cohort consisting of 140 urology controls & 96 tumors (56 de novo, 40 recurrent). Model validation was performed in two studies: first a multi-institutional case-control design with 96 controls & 70 UC cases (22 de novo, 48 surveillance); a second using a nested case-control design within the prospective Golestan Cohort Study (50,045 participants). The nested cohort consisted of 29 asymptomatic individuals who subsequently developed primary UC (median time to UC 7.3 yrs) and 98 matched controls (median f/u 6.1 yrs). RESULTS: The UC screening model was trained to a sensitivity of 88% (97% sensitivity for HG) and specificity of 94%. In the first validation, a sensitivity of 86% in de novo (87% for HG), 71% overall (de novo + recurrent tumors), and specificity 94% was observed. In the Golestan cohort, baseline muCGP had a prediction sensitivity of 66% (71% for HG) and specificity 94% was observed (Figure 1A). In contrast baseline TERT predicted 48% percent of cancers with a specificity of 100%. Cancer-free survival was significantly worse in muGCP-predicted positives vs. muGCP-predicted negatives (HR 8.5, 95% CI 3.8 – 18.4, p<0.0001). When limited to UC diagnosis within five years, UroAmp detected pre-clinical UC in 90% of future cancers (Figure 1B), compared to a sensitivity of 57% using TERT mutations alone. CONCLUSIONS: Our results provide the first evidence from a population-based prospective cohort study of pre-clinical UC detection with muCGP. muCGP identifies 9 of 10 cancers that occur within the first 5 years while detecting 10 of 19 cancers that occur beyond 5 years. Further studies will determine the frequency of muCGP screening required to maximize cancer detection and refine clinical interventions to save lives. Source of Funding: Convergent Genomics with a grant from the National Cancer Institute Small Business Innovation Research Program, 5R44CA200174-05 © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e304 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yair Lotan More articles by this author Keyan Salari More articles by this author Adam Feldman More articles by this author Debasish Sundi More articles by this author Jason J Lee More articles by this author Gabrielle DiFiore More articles by this author Hossein Poustchi More articles by this author Masoud Khoshnia More articles by this author Gholamreza Roshandel More articles by this author Arash Etemadi More articles by this author Mahdi Goudarzi More articles by this author Peter S. Lentz More articles by this author Kevin G. Phillips More articles by this author Vincent T. Bicocca More articles by this author Theresa M. Koppie More articles by this author Joe W. Gray More articles by this author Trevor Levin More articles by this author Reza Malekzadeh More articles by this author Mahdi Sheikh More articles by this author Florence Le Calvez-Kelm More articles by this author Expand All Advertisement PDF downloadLoading ...