PD42-01 RESIDUAL MUSCLE-INVASIVE DISEASE AT CYSTECTOMY IS NOT ACCURATELY PREDICTED BY POST-CHEMOTHERAPY RESTAGING PROTOCOLS INCLUDING DNA DAMAGE RESPONSE GENE MUTATION ANALYSIS

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology III (PD42)1 Apr 2020PD42-01 RESIDUAL MUSCLE-INVASIVE DISEASE AT CYSTECTOMY IS NOT ACCURATELY PREDICTED BY POST-CHEMOTHERAPY RESTAGING PROTOCOLS INCLUDING DNA DAMAGE RESPONSE GENE MUTATION ANALYSIS Russell Becker*, Alex Baras, Alexa Meyer, Aaron Brant, Adam Reese, George Netto, Andres Matoso, Jean Hoffman-Censits, Noah Hahn, Woonyoung Choi, David McConkey, Phillip Pierorazio, Michael Johnson, Mark Schoenberg, Max Kates, and Trinity Bivalacqua Russell Becker*Russell Becker* More articles by this author , Alex BarasAlex Baras More articles by this author , Alexa MeyerAlexa Meyer More articles by this author , Aaron BrantAaron Brant More articles by this author , Adam ReeseAdam Reese More articles by this author , George NettoGeorge Netto More articles by this author , Andres MatosoAndres Matoso More articles by this author , Jean Hoffman-CensitsJean Hoffman-Censits More articles by this author , Noah HahnNoah Hahn More articles by this author , Woonyoung ChoiWoonyoung Choi More articles by this author , David McConkeyDavid McConkey More articles by this author , Phillip PierorazioPhillip Pierorazio More articles by this author , Michael JohnsonMichael Johnson More articles by this author , Mark SchoenbergMark Schoenberg More articles by this author , Max KatesMax Kates More articles by this author , and Trinity BivalacquaTrinity Bivalacqua More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000922.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The standard of care for eligible patients with muscle-invasive bladder cancer (MIBC) includes neoadjuvant cisplatin-based chemotherapy (NAC), followed by radical cystectomy and urinary diversion (RC). Deleterious DNA damage response (DDR) gene mutations have been correlated with favorable response to NAC. Several groups have proposed that including DDR mutation analysis in post-NAC restaging algorithms may help define a subset of favorable responders who can safely forego RC. We sought to test this hypothesis in a cohort of patients undergoing NAC and RC. METHODS: We identified patients in our institutional RC registry who underwent a prospective protocol of post-NAC restaging prior to RC, between 2003 and 2016. Tumor DNA was captured from pre-NAC tumor specimens, and sequenced for mutations in the DDR genes ATM, RB1, ERCC2, and FANCC by Illumina HiSeq. Pathologic stages based on post-NAC restaging findings (rT) and final pathologic evaluation of the RC specimen (pT) were categorized into ≤ T1 (including carcinoma in situ) or ≥ T2, as this represents a critical inflection point in both prognosis and management strategy. RESULTS: A total of 47 patients received adequate NAC followed by restaging and RC, and had tumor tissue available for sequencing. Of these, 31 (66%) had DDR mutations, with ATM mutations being the most prevalent (21/47, 45%). Restaging and pathologic T-stage categories were concordant in 38/47 patients overall (81%), and 24/31 DDR(+) patients (77%). For patients with ≤ rT1 on post-NAC restaging, final RC pathology revealed residual muscle-invasive disease (≥ pT2) in 7/25 patients overall (28%), and 5/15 DDR(+) patients (33%, Fisher’s exact test p=0.66). CONCLUSIONS: For some favorable responders, MIBC can be downstaged or even eradicated by NAC alone. However, current restaging protocols lack the precision to reliably identify these patients, as evidenced by the 7 patients falsely downstaged in our series. The addition of DDR gene mutation analysis to restaging protocols does not enhance their accuracy. Until better discriminators are developed, post-NAC restaging and DDR mutations should not be routinely used to guide management decisions. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e827-e827 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Russell Becker* More articles by this author Alex Baras More articles by this author Alexa Meyer More articles by this author Aaron Brant More articles by this author Adam Reese More articles by this author George Netto More articles by this author Andres Matoso More articles by this author Jean Hoffman-Censits More articles by this author Noah Hahn More articles by this author Woonyoung Choi More articles by this author David McConkey More articles by this author Phillip Pierorazio More articles by this author Michael Johnson More articles by this author Mark Schoenberg More articles by this author Max Kates More articles by this author Trinity Bivalacqua More articles by this author Expand All Advertisement PDF downloadLoading ...