Late cell cycle signatures stratify gemdoce responses for bcg-unresponsive non-muscle invasive bladder cancer

You have accessJournal of UrologyCME1 Apr 2023MP14-16 LATE CELL CYCLE SIGNATURES STRATIFY GEMDOCE RESPONSES FOR BCG-UNRESPONSIVE NON-MUSCLE INVASIVE BLADDER CANCER Andrew Gabrielson, Gabriel Epstein, Mingxiao Feng, Sunil Patel, Max Kates, and Woonyoung Choi Andrew GabrielsonAndrew Gabrielson More articles by this author , Gabriel EpsteinGabriel Epstein More articles by this author , Mingxiao FengMingxiao Feng More articles by this author , Sunil PatelSunil Patel More articles by this author , Max KatesMax Kates More articles by this author , and Woonyoung ChoiWoonyoung Choi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003234.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Patients with BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) are commonly treated with intravesical gemcitabine and docetaxel chemotherapy (GEMDOCE). However, studies evaluating biomarkers of GEMDOCE response in BCG-unresponsive NMIBC have been limited. Docetaxel is a microtubule-stabilizing agent that induces cell cycle arrest and apoptosis through mitotic catastrophe. We evaluated whether early and late cell cycle signatures were associated with GEMDOCE response in BCG-unresponsive NMIBC tumors. METHODS: We performed a retrospective study of patients with BCG-unresponsive NMIBC who underwent intravesical GEMDOCE. Monthly maintenance therapy was given for 52% of patients with a 3-month complete response. RNAseq and DNA panel sequencing were performed on FFPE tissues from pre-treatment TURBT samples. Gene set variation analysis (GSVA) was performed to calculate gene set enrichment scores with cell cycle and immune signatures. Cluster analysis was performed to assess whether cell-cycle signatures and other gene signatures were associated with response and recurrence-free survival. RESULTS: A total of 30 patients with BCG-unresponsive NMIBC were included, of whom 63% (19) experienced disease recurrence. Cluster analysis with cell cycle signatures yielded 2 clusters with high expression of either late (cluster 1) or early (cluster 2) cell cycle signatures (Figure 1). Tumors enriched with late cell cycle signatures showed significant recurrence-free survival benefit compared to tumors with high expression of early cell cycle signatures (Figure 2). TP53 alterations were enriched in cluster 1 which demonstrated a clinical benefit from GEMDOCE. In contrast to prior work from our lab on BCG-treated tumors, response in GEMDOCE-treated tumors was not associated with immune signatures. CONCLUSIONS: These early data suggest that there may be molecular signatures that stratify patients with BCG-unresponsive NMIBC treated with GEMDOCE. Further expansion of these cohorts in both BCG-naïve and BCG-unresponsive cohorts is ongoing. Source of Funding: NA © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e188 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrew Gabrielson More articles by this author Gabriel Epstein More articles by this author Mingxiao Feng More articles by this author Sunil Patel More articles by this author Max Kates More articles by this author Woonyoung Choi More articles by this author Expand All Advertisement PDF downloadLoading ...