PD58-02 NOVEL USE OF CTDNA TO IDENTIFY LOCALLY ADVANCED AND METASTATIC UPPER TRACT UROTHELIAL CARCINOMA (2022)

You have accessJournal of UrologyCME1 May 2022PD58-02 NOVEL USE OF CTDNA TO IDENTIFY LOCALLY ADVANCED AND METASTATIC UPPER TRACT UROTHELIAL CARCINOMA Heather Huelster, Elizabeth Green, Alex Soupir, Kyle Rose, Esther Katende, Shreyas Naidu, Scott Gilbert, Brandon Manley, Michael Poch, Wade Sexton, Alice Yu, Youngchul Kim, Pan Du, Shidong Jia, Il-Jin Kim, Lu Tan, Liang Wang, and Roger Li Heather HuelsterHeather Huelster More articles by this author , Elizabeth GreenElizabeth Green More articles by this author , Alex SoupirAlex Soupir More articles by this author , Kyle RoseKyle Rose More articles by this author , Esther KatendeEsther Katende More articles by this author , Shreyas NaiduShreyas Naidu More articles by this author , Scott GilbertScott Gilbert More articles by this author , Brandon ManleyBrandon Manley More articles by this author , Michael PochMichael Poch More articles by this author , Wade SextonWade Sexton More articles by this author , Alice YuAlice Yu More articles by this author , Youngchul KimYoungchul Kim More articles by this author , Pan DuPan Du More articles by this author , Shidong JiaShidong Jia More articles by this author , Il-Jin KimIl-Jin Kim More articles by this author , Lu TanLu Tan More articles by this author , Liang WangLiang Wang More articles by this author , and Roger LiRoger Li More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002643.02AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Upper tract urothelial carcinoma (UTUC) is an aggressive cancer for which use of neoadjuvant chemotherapy (NAC) is limited by suboptimal clinical staging prior to nephroureterectomy. Detection of circulating tumor DNA (ctDNA) is associated with locally advanced and metastatic urothelial carcinoma of the bladder and may help identify UTUC patients who would benefit from NAC. Here we examine the feasibility and utility of plasma ctDNA in the diagnosis of non-organ confined high-risk UTUC. METHODS: Patients with high-grade cTa-T2 UTUC without radiographic evidence of metastases undergoing up-front radical nephroureterectomy (RNU) were prospectively accrued. Blood was collected preoperatively, and plasma and buffy coat were processed for extraction of ctDNA. FFPE samples from RNU were used for tissue genomic DNA extraction. Next-generation sequencing (NGS) profiled variants. Plasma and somatic mutations were called by comparing with matched buffy coat samples. Detection of cancer variants with a mutation allele frequency (MAF) ≥ 0.25% and hotspot variants with MAF down to 0.1% were reported for plasma targeted by a NGS panel (PredicineCARE). Variants with MAF ≥ 5% and hotspot variants with MAF to 2% were reported for FFPE. RESULTS: NGS analyses of matched FFPE and plasma were successfully performed for all 15 accrued UTUC patients. Alterations in MYC amplification (62%), TERT promoter (62%), TP53 (38%), FGFR3 (31%), ERBB2 (25%), ARID1A (19%), and PIK3CA (19%) were demonstrated in urothelial tumor tissue. Matched plasma ctDNA showed prevalent alterations in the TERT promoter (47%), TP53 (30%), ARID1A (20%), ERBB2 (20%), FGFR3 (20%), and PIK3CA (17%). Five patients (33%) had detectable plasma ctDNA mutations concordant with tumor-based genotypes using the targeted NGS panel (Figure 1). All patients with detectable preoperative ctDNA had advanced staging (≥pT2 or ≥pN1) and lymphovascular invasion on final pathology, resulting in a 71.4% sensitivity. The panel was 100% specific with no patients with pTis, pTa, pT1 and pN0 having detectable concordant ctDNA mutations. CONCLUSIONS: Prospective ctDNA analysis using a targeted NGS panel is a feasible nonsurgical approach to prediction of high-risk UTUC and has the potential for identification of upper tract urothelial cancer patients that may benefit from NAC. Source of Funding: Predicine Inc © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e1011 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Heather Huelster More articles by this author Elizabeth Green More articles by this author Alex Soupir More articles by this author Kyle Rose More articles by this author Esther Katende More articles by this author Shreyas Naidu More articles by this author Scott Gilbert More articles by this author Brandon Manley More articles by this author Michael Poch More articles by this author Wade Sexton More articles by this author Alice Yu More articles by this author Youngchul Kim More articles by this author Pan Du More articles by this author Shidong Jia More articles by this author Il-Jin Kim More articles by this author Lu Tan More articles by this author Liang Wang More articles by this author Roger Li More articles by this author Expand All Advertisement PDF DownloadLoading ...