PD09-07 ASSESSING THE UTILITY OF A CELL-FREE TUMOR (ct)DNA ASSAY (MSK-ACCESS) IN NODE POSITIVE (N+) MUSCLE INVASIVE BLADDER CANCER (MIBC) PATIENTS (pts) UNDERGOING NEOADJUVANT CHEMOTHERAPY (NAC)

The Journal of Urology(2023)

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You have accessJournal of UrologyCME1 Apr 2023PD09-07 ASSESSING THE UTILITY OF A CELL-FREE TUMOR (ct)DNA ASSAY (MSK-ACCESS) IN NODE POSITIVE (N+) MUSCLE INVASIVE BLADDER CANCER (MIBC) PATIENTS (pts) UNDERGOING NEOADJUVANT CHEMOTHERAPY (NAC) Andrew B. Katims, Andrew T. Lenis, Ronak H. Shah, Carissa E. Chu, Neha Ratna, Ashely M. Regazzi, Eugene J. Pietzak, David H. Aggen, Samuel A. Funt, Min Yuen Teo, Jonathan E. Rosenberg, Dean F. Bajorin, Timothy F. Donahue, Bernard H. Bochner, Michael F. Berger, David B. Solit, and Gopa Iyer Andrew B. KatimsAndrew B. Katims More articles by this author , Andrew T. LenisAndrew T. Lenis More articles by this author , Ronak H. ShahRonak H. Shah More articles by this author , Carissa E. ChuCarissa E. Chu More articles by this author , Neha RatnaNeha Ratna More articles by this author , Ashely M. RegazziAshely M. Regazzi More articles by this author , Eugene J. PietzakEugene J. Pietzak More articles by this author , David H. AggenDavid H. Aggen More articles by this author , Samuel A. FuntSamuel A. Funt More articles by this author , Min Yuen TeoMin Yuen Teo More articles by this author , Jonathan E. RosenbergJonathan E. Rosenberg More articles by this author , Dean F. BajorinDean F. Bajorin More articles by this author , Timothy F. DonahueTimothy F. Donahue More articles by this author , Bernard H. BochnerBernard H. Bochner More articles by this author , Michael F. BergerMichael F. Berger More articles by this author , David B. SolitDavid B. Solit More articles by this author , and Gopa IyerGopa Iyer More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003240.07AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Circulating ctDNA is associated with disease progression, worse overall survival, and recurrence in pts with bladder cancer. This study correlated targeted exome ctDNA sequencing with pathologic response to NAC and metastatic recurrence in pts with N+ MIBC undergoing radical cystectomy (RC). METHODS: We prospectively identified pts with cT2-3N1-2M0 bladder cancer who underwent NAC prior to RC. Node positivity was determined radiographically and/or by node biopsy. Plasma samples were collected pre-NAC, mid-treatment, after NAC completion, and 3 months after RC. Samples were analyzed using MSK-ACCESS, an ultrasensitive ctDNA platform designed to identify somatic mutations in 129 cancer associated genes. Primary bladder tumors were sequenced using targeted exome sequencing. RESULTS: 31 samples from 9 pts (6 men) were analyzed. Median age was 63 years (IQR 58-69). NAC regimens included gemcitabine and cisplatin alone (78%) or with paclitaxel (22%). Seven (78%) pts had >1 detectable mutation pre-NAC. The most altered genes detected in both tissue and ctDNA included: TERT (88% vs 28%), TP53 (76% vs 40%), ARID1A (43% vs 17%), RB1 (43% vs 15%), KDM6A (43% vs 15%), and ATM (17% vs 17%). Four (45%) pts had complete response (ypT0N0), 1 (11%) had a partial response (ypT1N0), and 4 (33.3%) were non-responders (ypT2N0-3). All non-responders had disease recurrence after RC (median 3 months, range 2-11 months). Of 7 pts with on-treatment MSK-ACCESS, 2 (29%) had detectable ctDNA (1 ypT2N0, 1 ypT0N0). The pt with a PR had detectable ctDNA post-NAC with 1 mutation identified that was not detected at 3 months. All pts with >ypT2N0 had detectable ctDNA post-NAC. Pts with recurrence/non-responders had a significantly higher mutation count 3 months after RC compared to responders, with a median of 7 vs. 0 mutations, respectively. Two pts with CR had detectable ctDNA at 3 months post-RC but have not recurred (Table 1). CONCLUSIONS: Clearance of ctDNA post-NAC correlated with pathologic complete response. Approximately 70% of pts had ctDNA clearance on NAC. All pts with residual disease at RC had detectable ctDNA post-NAC. N+ disease correlated with persistent ctDNA detected at 3 months post-RC. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e242 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrew B. Katims More articles by this author Andrew T. Lenis More articles by this author Ronak H. Shah More articles by this author Carissa E. Chu More articles by this author Neha Ratna More articles by this author Ashely M. Regazzi More articles by this author Eugene J. Pietzak More articles by this author David H. Aggen More articles by this author Samuel A. Funt More articles by this author Min Yuen Teo More articles by this author Jonathan E. Rosenberg More articles by this author Dean F. Bajorin More articles by this author Timothy F. Donahue More articles by this author Bernard H. Bochner More articles by this author Michael F. Berger More articles by this author David B. Solit More articles by this author Gopa Iyer More articles by this author Expand All Advertisement PDF downloadLoading ...
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muscle invasive bladder cancer,neoadjuvant chemotherapy,cell-free,msk-access
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