MP49-02 A STUDY TO EVALUATE THE PROGNOSTIC AND PREDICTIVE UTILITY OF CCP AND HRD ASSAYS AND GENETIC SEQUENCING IN PATIENTS UNDERGOING NEOADJUVANT CHEMOTHERAPY IN BLADDER CANCER
2016-03-28

You have accessJournal of UrologyBladder Cancer: Invasive III1 Apr 2016MP49-02 A STUDY TO EVALUATE THE PROGNOSTIC AND PREDICTIVE UTILITY OF CCP AND HRD ASSAYS AND GENETIC SEQUENCING IN PATIENTS UNDERGOING NEOADJUVANT CHEMOTHERAPY IN BLADDER CANCER Hristos Kaimakliotis, Michael Koch, Lee-Wei Kao, Jane Cho, Richard Bihrle, Roberto Pili, Clint Cary, Timothy Masterson, Costantine Albany, Richard Foster, Julia Reid, Kirsten Timms, Liang Cheng, and Steve Stone Hristos KaimakliotisHristos Kaimakliotis More articles by this author , Michael KochMichael Koch More articles by this author , Lee-Wei KaoLee-Wei Kao More articles by this author , Jane ChoJane Cho More articles by this author , Richard BihrleRichard Bihrle More articles by this author , Roberto PiliRoberto Pili More articles by this author , Clint CaryClint Cary More articles by this author , Timothy MastersonTimothy Masterson More articles by this author , Costantine AlbanyCostantine Albany More articles by this author , Richard FosterRichard Foster More articles by this author , Julia ReidJulia Reid More articles by this author , Kirsten TimmsKirsten Timms More articles by this author , Liang ChengLiang Cheng More articles by this author , and Steve StoneSteve Stone More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.415AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In an effort to identify potential biomarkers in urothelial bladder cancer (UBC) that will aid in characterizing disease aggressiveness and/or predict cisplatin chemo-sensitivity, we explored the utility of a combination of nucleic acid-based assays. METHODS Between 2003 and 2014 formalin-fixed paraffin-embedded bladder tumor from time of TURBT was obtained from patients before treatment with neoadjuvant chemotherapy (NACT). All patients had muscle invasive UBC and underwent radical cystectomy. Molecular assays included the cell cycle progression (CCP) score, the homologous recombination deficiency (HRD) score, and genetic sequencing of a set of genes recently implicated as potential drivers in UBC. CCP and HRD scores and gene mutations were correlated to complete pathologic response (pCR) and disease recurrence. RESULTS A total of 90 samples were obtained from patients who underwent NACT followed by cystectomy, of which 70 patient samples were able to yield both CCP and HRD scores. Higher CCP and HRD scores were associated with pCR on univariate analysis (OR 2.39, CI 1.15-4.95, p= 0.011 and OR 2.10, CI 1.04-4.22, p= 0.033, respectively), but not when adjusting for each other, indicating that CCP and HRD do not provide significant independent predictive information. An HRD score greater than 30 (4th quartile) was associated with a decreased risk of recurrence, and remained predictive of decreased recurrence when accounting for pCR (p=0.019). Among 82 genes sequenced, mutations identified in RB1 and TP53 genes were associated with pCR (p=0.0040 and p=0.030, respectively). Best multivariable models for pCR were either RB1 and CCP (OR 3.70, CI 1.14-12.1, p=0.028 and OR 2.50, CI 0.93-6.74, p=0.053, respectively); or RB1 and HRD (OR 4.24, CI 1.38-14.1, p=0.011 and OR 1.95, CI 0.91-4.21, 0.081). CONCLUSIONS RB1 mutations are associated with response to cisplatin NACT in UBC patients. The predictive ability appears to be improved by the addition of either CCP or HRD scores. If validated, these tests could be used to help identify chemo-responsive patients. In addition, HRD could be used to predict risk of recurrence in patients after NACT followed by cystectomy. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e664-e665 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Hristos Kaimakliotis More articles by this author Michael Koch More articles by this author Lee-Wei Kao More articles by this author Jane Cho More articles by this author Richard Bihrle More articles by this author Roberto Pili More articles by this author Clint Cary More articles by this author Timothy Masterson More articles by this author Costantine Albany More articles by this author Richard Foster More articles by this author Julia Reid More articles by this author Kirsten Timms More articles by this author Liang Cheng More articles by this author Steve Stone More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...