PD47-11 RAPID ORGANOID DEVELOPMENT, DRUG SCREENING, AND NEOADJUVANT CHEMOTHERAPY RESPONSE PREDICTION FOR PATIENTS WITH LOCALLY-ADVANCED BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology IV (PD47)1 Apr 2020PD47-11 RAPID ORGANOID DEVELOPMENT, DRUG SCREENING, AND NEOADJUVANT CHEMOTHERAPY RESPONSE PREDICTION FOR PATIENTS WITH LOCALLY-ADVANCED BLADDER CANCER Kathryn A Marchetti*, Nathan Merrill, Nathalie Vandecan, Liwei Bao, Xu Cheng, Aaron Udager, Lindsey A Herrel, Jeffery Montgomery, Khaled Hafez, Todd Morgan, Alon Weizer, Ajjai Alva, Matthew Soellner, Sofia Merajver, and Samuel Kaffenberger Kathryn A Marchetti*Kathryn A Marchetti* More articles by this author , Nathan MerrillNathan Merrill More articles by this author , Nathalie VandecanNathalie Vandecan More articles by this author , Liwei BaoLiwei Bao More articles by this author , Xu ChengXu Cheng More articles by this author , Aaron UdagerAaron Udager More articles by this author , Lindsey A HerrelLindsey A Herrel More articles by this author , Jeffery MontgomeryJeffery Montgomery More articles by this author , Khaled HafezKhaled Hafez More articles by this author , Todd MorganTodd Morgan More articles by this author , Alon WeizerAlon Weizer More articles by this author , Ajjai AlvaAjjai Alva More articles by this author , Matthew SoellnerMatthew Soellner More articles by this author , Sofia MerajverSofia Merajver More articles by this author , and Samuel KaffenbergerSamuel Kaffenberger More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000934.011AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Neoadjuvant chemotherapy prior to radical cystectomy (RC) for muscle-invasive urothelial carcinoma is the standard of care despite a small absolute survival benefit and the potential for disease progression during chemotherapy. While progress has been made in the prediction of sensitivity to platinum-based chemotherapies, providing more accurate, personalized, and clinically-relevant chemotherapy response prediction is an unmet need. We present our early and ongoing experience with rapid, organoid-based drug-screening. METHODS: From patients undergoing a transurethral resection of bladder tumor or RC, 1 gram of tumor was procured and divided between DNA/RNA sequencing, organoid drug-screening, and patient-derived xenografts. Tissue was dissociated, filtered, and resuspended in organoid media for serial passage and drug screening. Drugs were tested at the maximum plasma concentration in human trials, so to provide physiologic relevance. Results were normalized to control such that a value of “100” indicated no difference in organoid viability compared to control, and a value of 0 indicated complete response. The number of drugs screened was dependent upon tissue available, but was often 20-30. RESULTS: Thus far, 25 patients have undergone rapid organoid development and drug testing. Drug response analyses were available on average 5-10 days following the procedure. Secondary to limited space, select drug response data from the 20 most recent patient organoid (org) samples are presented (Figure 1). All patients have DNA and RNA sequencing and PDX models in progress. CONCLUSIONS: Rapid organoid development and drug screening allows for the determination of neoadjuvant chemotherapy response within 5-10days. Use of this technique on tissue provided during disease work-up may further guide selection of effective therapeutic agents in patients with bladder cancer. This would overall minimize the morbidity of standard of care therapies. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e929-e929 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kathryn A Marchetti* More articles by this author Nathan Merrill More articles by this author Nathalie Vandecan More articles by this author Liwei Bao More articles by this author Xu Cheng More articles by this author Aaron Udager More articles by this author Lindsey A Herrel More articles by this author Jeffery Montgomery More articles by this author Khaled Hafez More articles by this author Todd Morgan More articles by this author Alon Weizer More articles by this author Ajjai Alva More articles by this author Matthew Soellner More articles by this author Sofia Merajver More articles by this author Samuel Kaffenberger More articles by this author Expand All Advertisement PDF downloadLoading ...