MP65-08 OPTIMIZING AN ORGANOID ASSAY FOR PREDICTING INTRAVESICAL THERAPY RESPONSE IN LOW-GRADE INTERMEDIATE RISK NON-MUSCLE INVASIVE BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology III (MP65)1 May 2024MP65-08 OPTIMIZING AN ORGANOID ASSAY FOR PREDICTING INTRAVESICAL THERAPY RESPONSE IN LOW-GRADE INTERMEDIATE RISK NON-MUSCLE INVASIVE BLADDER CANCER Benjamin I. Joffe, John R. Christin, Clémentine Le Coz, Caroline Laplaca, G. Joel DeCastro, Christopher B. Anderson, James M. McKiernan, Michael Shen, and Andrew T. Lenis Benjamin I. JoffeBenjamin I. Joffe , John R. ChristinJohn R. Christin , Clémentine Le CozClémentine Le Coz , Caroline LaplacaCaroline Laplaca , G. Joel DeCastroG. Joel DeCastro , Christopher B. AndersonChristopher B. Anderson , James M. McKiernanJames M. McKiernan , Michael ShenMichael Shen , and Andrew T. LenisAndrew T. Lenis View All Author Informationhttps://doi.org/10.1097/01.JU.0001008756.24343.22.08AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: For patients with intermediate-risk non-muscle invasive bladder cancer (IR-NMIBC), standard of care involves transurethral resection (TUR) potentially followed by intravesical therapy (IVT). Various conventional chemotherapies are used for IVT; however, limited data exist to compare the efficacy of these options. This assay seeks to quantify the most effective IVT choice for each IR-NMIBC patient with the goal of finding genetic predictors and outcome validation via clinical trial. METHODS: Patients with suspected IR-NMIBC were identified. Cold-cup biopsies were taken to obtain tumor tissue. Patient-derived organoids (PDOs) were created immediately on Day 0 using previously described methods. On Day 1, a selection of IVT were added to PDOs as monotherapies in serial dilutions: cisplatin, gemcitabine, docetaxel, cabazitaxel, mitomycin C (MMC), and valrubicin. On Day 6, PDO viability was calculated using luminometer and dose response curves with IC50s were created. Single cell and cluster formations were compared. RESULTS: Twelve fresh PDOs were tested, of which six are confirmed low grade (LG) IR-NMIBC. Four established bladder cancer organoids (SCBOs) were tested for comparison, including three LG lines. MMC was the most effective IVT in eight (67%), valrubicin was the most effective in three (25%), and cabazitaxel and cisplatin were each most effective in one (8%). Among LG PDOs, most effective IVT was MMC in three (50%), valrubicin in two (33%), and cisplatin in one (17%). Among SCBOs, MMC and valrubicin were each most effective IVT In two (50%). In three PDOs, gemcitabine IC50 could not be calculated as all concentrations produced a response. There was little difference in IC50s between PDOs plated and treated as single cells versus clusters. Further passaging to compare response in early versus late PDOs is ongoing. CONCLUSIONS: This PDO assay can identify the most effective IVT in vitro within a clinically relevant time frame. In multiple patients, the assay-determined most effective IVT would have changed clinical management. Further optimization and implementation of this assay as a corollary in clinical trials could be used to glean meaningful insights into mechanisms of sensitivity and resistance. Source of Funding: N/A © 2024 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 211Issue 5SMay 2024Page: e1079 Advertisement Copyright & Permissions© 2024 by American Urological Association Education and Research, Inc.Metrics Author Information Benjamin I. Joffe More articles by this author John R. Christin More articles by this author Clémentine Le Coz More articles by this author Caroline Laplaca More articles by this author G. Joel DeCastro More articles by this author Christopher B. Anderson More articles by this author James M. McKiernan More articles by this author Michael Shen More articles by this author Andrew T. Lenis More articles by this author Expand All Advertisement PDF downloadLoading ...