Mp35-05 Developing Non-Invasive and Cost-Effective Methods for Urothelial Cancer Detection and Surveillance Using a Urine Dna Panel (Uroscout Assay)

You have accessJournal of UrologyBladder Cancer: Epidemiology & Evaluation II (MP35)1 May 2024MP35-05 DEVELOPING NON-INVASIVE AND COST-EFFECTIVE METHODS FOR UROTHELIAL CANCER DETECTION AND SURVEILLANCE USING A URINE DNA PANEL (UROSCOUT ASSAY) Jussi Nikkola, Thea Veitonmäki, Lauri Ryyppö, Juuso Vuorinen, Heini Kallio, Hanna Selin, Pyry Jämsä, Antti Kaipia, Tarmo Pekkarinen, Jonne Åkerla, Matti Nykter, and Matti Annala Jussi NikkolaJussi Nikkola , Thea VeitonmäkiThea Veitonmäki , Lauri RyyppöLauri Ryyppö , Juuso VuorinenJuuso Vuorinen , Heini KallioHeini Kallio , Hanna SelinHanna Selin , Pyry JämsäPyry Jämsä , Antti KaipiaAntti Kaipia , Tarmo PekkarinenTarmo Pekkarinen , Jonne ÅkerlaJonne Åkerla , Matti NykterMatti Nykter , and Matti AnnalaMatti Annala View All Author Informationhttps://doi.org/10.1097/01.JU.0001009372.61513.54.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The detection of cancer-associated DNA in urine samples has significant potential in urothelial cancer detection and surveillance, but current assays tend to miss low grade tumors. This study aimed to develop a cost-effective diagnostic panel capable of identifying all clinical stages of urothelial cancer. METHODS: Up to 100 mL of urine at the time of the first surgery for urothelial carcinoma was prospectively collected from patients. We developed a hybridization capture assay targeting the coding regions of 21 commonly mutated genes in urothelial tumors, as well as 8 frequently copy number altered loci. Samples were sequenced using Illumina NovaSeq instruments. Mutations, copy number alterations, and chromosomal rearrangements were computationally identified. RESULTS: From January 2021 to September 2023, we collected urine samples from 134 patients with pathologically confirmed bladder cancer and 27 patients with upper tract urothelial carcinoma (UTUC), clinically representing a comprehensive cohort of urothelial cancer cases. Our diagnostic assay achieved high sensitivity in detecting overall bladder cancer (104/106 detected, 98%), pTa low grade bladder cancer (48/49 detected, 98%) and UTUC (21/23 detected, 91%). We also analyzed 177 post-operative urine samples from 94 patients and detected residual cancer in 18/20 (90%) samples where a time-matched cystoscopy or surgical tissue was positive, with only two pTa low grade recurrences missed. We compared urine cell pellet DNA and urine cell-free DNA, finding similar fractions of cancer DNA across these analytes but higher DNA yields (median 9.91 ng/mL vs. 2.95 ng/mL) and higher molecular weight DNA in the urine cell pellet. Three UTUC patients carried germline defects in mismatch repair genes MSH2 or MSH6, indicative of Lynch syndrome. In two of these patients our panel also found a somatic second hit and high mutation load. The assay's specificity was 93%, determined using 95 negative control samples from hematuria, kidney cancer, and healthy individuals. CONCLUSIONS: These results using the UroScout diagnostic assay show promise in urine DNA based cancer diagnostics even in patients with pTa low grade tumors. The panel is designed to offer a non-invasive and cost-effective alternative for cystoscopies. Source of Funding: Jane and Aatos Erkko Foundation, Finnish Medical Foundation, Sigrid Juselius Foundation, Finnish Urological Research Fund, Pirkanmaa Cancer Foundation, Finnish Cancer Foundation, Tampere University Hospital Competitive Research Fund © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e582 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Jussi Nikkola More articles by this author Thea Veitonmäki More articles by this author Lauri Ryyppö More articles by this author Juuso Vuorinen More articles by this author Heini Kallio More articles by this author Hanna Selin More articles by this author Pyry Jämsä More articles by this author Antti Kaipia More articles by this author Tarmo Pekkarinen More articles by this author Jonne Åkerla More articles by this author Matti Nykter More articles by this author Matti Annala More articles by this author Expand All Advertisement PDF downloadLoading ...