PD46-11 ASSESSING THE ROLE OF NEOADJUVANT CHEMOTHERAPY IN UPPER TRACT UROTHELIAL CARCINOMA EVOLUTION

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You have accessJournal of UrologyCME1 Apr 2023PD46-11 ASSESSING THE ROLE OF NEOADJUVANT CHEMOTHERAPY IN UPPER TRACT UROTHELIAL CARCINOMA EVOLUTION Neeta D'Souza, Andrew B. Katims, Ali Mouzannar, Eugene J. Pietzak, David Solit, Kwanghee Kim, and Jonathan A. Coleman Neeta D'SouzaNeeta D'Souza More articles by this author , Andrew B. KatimsAndrew B. Katims More articles by this author , Ali MouzannarAli Mouzannar More articles by this author , Eugene J. PietzakEugene J. Pietzak More articles by this author , David SolitDavid Solit More articles by this author , Kwanghee KimKwanghee Kim More articles by this author , and Jonathan A. ColemanJonathan A. Coleman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003359.11AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Systemic neoadjuvant chemotherapy (NAC) may apply selective pressure on tumors and shape cancer evolution. In bladder cancer, intratumor genetic heterogeneity can help predict response to NAC, with RB1, ERCC2, ATM, and FANCC mutations significantly associated with a positive response to NAC. Molecular studies have shown upper tract urothelial carcinoma (UTUC) to be genetically distinct from bladder cancer with a significantly worse response to NAC, yet still harboring significant intratumor heterogeneity. This study aims to assess the effect of NAC in selecting chemotherapy-resistant mutations among the intratumor heterogeneity in UTUC. METHODS: We identified patients with UTUC who underwent platinum-based NAC followed by nephroureterectomy treated at Memorial Sloan Kettering Cancer Center. Patients with complete response to NAC were excluded. Pre-NAC biopsy and post-NAC nephroureterectomy samples underwent next generation targeted gene sequencing through MSK-IMPACT. Mutational frequency among the 505 tested genes was compared in the pre-and post- treatment cohorts to assess for significant changes (p<0.05). RESULTS: We identified 15 patients with UTUC that had an incomplete response/progression of disease after NAC with gemcitabine/cisplatin as determined by final pathology at radical nephroureterectomy. The median age at the time of NAC was 60 (IQR 55-70). The most common mutations are seen in Figure 1. The most common mutated genes in pre-NAC UTUC biopsy were TERT (53.3%), KMT2D (40.0%), and ARID1A (33.3%). Post-chemotherapy, the most common mutations were TERT (56.3%), FGFR3 (31.3%), and KMT2D (31.3%). There were no significant differences between the frequency of mutations pre- and post-NAC. There was no decrease in the frequency of RB1, ERCC2, ATM, and FANCC post-NAC. CONCLUSIONS: Administration of NAC did not select for specific resistant mutations in the global tumor landscape. It is possible that changes to the tumor microenvironment, sub-clonal expansion, or differences in expression may be identified through RNA based studies. Source of Funding: N/A © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e1174 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Neeta D'Souza More articles by this author Andrew B. Katims More articles by this author Ali Mouzannar More articles by this author Eugene J. Pietzak More articles by this author David Solit More articles by this author Kwanghee Kim More articles by this author Jonathan A. Coleman More articles by this author Expand All Advertisement PDF downloadLoading ...