MP41-20 DEFINING THE UTILITY OF MSK-ACCESS, A CELL-FREE TUMOR DNA ASSAY, IN PATIENTS TREATED WITH RADICAL CYSTECTOMY FOR MUSCLE-INVASIVE BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Invasive II (MP41)1 Sep 2021MP41-20 DEFINING THE UTILITY OF MSK-ACCESS, A CELL-FREE TUMOR DNA ASSAY, IN PATIENTS TREATED WITH RADICAL CYSTECTOMY FOR MUSCLE-INVASIVE BLADDER CANCER Andrew T. Lenis, Charles Murphy, Timothy Clinton, Manuel de Jesus Escano, Hong Truong, Peter Reisz, Aditya Bagrodia, Nicholas Silva, Priscilla Baez, Ronak Shah, Christine Iacobuzio-Donahue, Eugene Pietzak, Michael Berger, David Solit, Gopa Iyer, Timothy Donahue, and Bernard Bochner Andrew T. LenisAndrew T. Lenis More articles by this author , Charles MurphyCharles Murphy More articles by this author , Timothy ClintonTimothy Clinton More articles by this author , Manuel de Jesus EscanoManuel de Jesus Escano More articles by this author , Hong TruongHong Truong More articles by this author , Peter ReiszPeter Reisz More articles by this author , Aditya BagrodiaAditya Bagrodia More articles by this author , Nicholas SilvaNicholas Silva More articles by this author , Priscilla BaezPriscilla Baez More articles by this author , Ronak ShahRonak Shah More articles by this author , Christine Iacobuzio-DonahueChristine Iacobuzio-Donahue More articles by this author , Eugene PietzakEugene Pietzak More articles by this author , Michael BergerMichael Berger More articles by this author , David SolitDavid Solit More articles by this author , Gopa IyerGopa Iyer More articles by this author , Timothy DonahueTimothy Donahue More articles by this author , and Bernard BochnerBernard Bochner More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002062.20AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Circulating cell-free tumor (cf) DNA in patients with bladder cancer has clinical utility in identification of minimal residual disease and prediction of recurrence after radical cystectomy. We report our experience with cfDNA detection and correlation with recurrence using a targeted exome cfDNA assay in patients with localized muscle-invasive bladder cancer. METHODS: We prospectively identified patients with cT2-3N0M0 bladder urothelial carcinoma undergoing radical cystectomy with curative intent. Plasma samples were obtained after transurethral resection, after neoadjuvant chemotherapy (if administered), and during follow-up for up to 3 years or until disease recurrence. Samples were analyzed with MSK-ACCESS, a cfDNA platform that sequences 129 genes and generates >15,000x coverage with detection of somatic mutations down to 0.1% mutant allele frequency. Primary tumor specimens were sequenced by targeted exome sequencing (MSK-IMPACT). RESULTS: A total of 72 samples were analyzed from 16 patients. The median age was 70 (IQR: 62-78) years, 75% were male, and 50% received 4 cycles of neoadjuvant gemcitabine and cisplatin. Of 11 patients with plasma drawn before treatment, 5 (45%) had detectable cfDNA; an additional 3 patients (73%) had detectable cfDNA when leveraging sequencing data from the primary tumor. All patients with detectable cfDNA had >pT2N0. Of 5 patients without detectable cfDNA, 2 had >pT2N0 and 3 had ≤pT1N0. Of 4 patients with pre- and post-neoadjuvant chemotherapy samples, 3 had detectable cfDNA pre-chemotherapy and 2 of 3 patients had detectable cfDNA post-chemotherapy, had pT3N1 disease at cystectomy, and developed metastatic recurrences. The third patient had clearance of cfDNA after chemotherapy and was pT0N0. Mutations unique to ACCESS were detected in 26 of 69 (38%) samples with available primary tumor sequencing. CONCLUSIONS: MSK-ACCESS can detect cfDNA in ∼75% of patients with localized bladder cancer. ACCESS appears specific for muscle-invasive disease. The negative predictive value was 60%. Up to one third of samples had mutations exclusive to ACCESS which may capture additional alterations missed by primary tumor sequencing due to intra- and inter-tumoral heterogeneity. Source of Funding: This research was supported by the Sidney Kimmel Center for Prostate and Urologic Cancers and funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748 © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e769-e769 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Andrew T. Lenis More articles by this author Charles Murphy More articles by this author Timothy Clinton More articles by this author Manuel de Jesus Escano More articles by this author Hong Truong More articles by this author Peter Reisz More articles by this author Aditya Bagrodia More articles by this author Nicholas Silva More articles by this author Priscilla Baez More articles by this author Ronak Shah More articles by this author Christine Iacobuzio-Donahue More articles by this author Eugene Pietzak More articles by this author Michael Berger More articles by this author David Solit More articles by this author Gopa Iyer More articles by this author Timothy Donahue More articles by this author Bernard Bochner More articles by this author Expand All Advertisement Loading ...