MP7-13 GENETIC SIGNATURES ARE ASSOCIATED WITH ADVERSE PATHOLOGIC AND CLINICAL OUTCOMES IN PATIENTS WITH UPPER TRACT UROTHELIAL CARCINOMA (UTUC)

Abstract

You have accessJournal of UrologyBladder Cancer: Upper Tract TCC II1 Apr 2015MP7-13 GENETIC SIGNATURES ARE ASSOCIATED WITH ADVERSE PATHOLOGIC AND CLINICAL OUTCOMES IN PATIENTS WITH UPPER TRACT UROTHELIAL CARCINOMA (UTUC) Aditya Bagrodia, Eugene Cha, John Sfakianos, Gopa Iyer, Byron Lee, Sasinya Scott, Emily Zabor, Ronak Shah, Qinghu Ren, Philip Kim, Ari Hakimi, Irina Ostrovnaya, Jonathan Rosenberg, Guido Dalbagni, Dean Bajorin, Victor Reuter, Michael Berger, Bernard Bochner, Hikmat Al-Ahmadie, David Solit, and Jonathan Coleman Aditya BagrodiaAditya Bagrodia More articles by this author , Eugene ChaEugene Cha More articles by this author , John SfakianosJohn Sfakianos More articles by this author , Gopa IyerGopa Iyer More articles by this author , Byron LeeByron Lee More articles by this author , Sasinya ScottSasinya Scott More articles by this author , Emily ZaborEmily Zabor More articles by this author , Ronak ShahRonak Shah More articles by this author , Qinghu RenQinghu Ren More articles by this author , Philip KimPhilip Kim More articles by this author , Ari HakimiAri Hakimi More articles by this author , Irina OstrovnayaIrina Ostrovnaya More articles by this author , Jonathan RosenbergJonathan Rosenberg More articles by this author , Guido DalbagniGuido Dalbagni More articles by this author , Dean BajorinDean Bajorin More articles by this author , Victor ReuterVictor Reuter More articles by this author , Michael BergerMichael Berger More articles by this author , Bernard BochnerBernard Bochner More articles by this author , Hikmat Al-AhmadieHikmat Al-Ahmadie More articles by this author , David SolitDavid Solit More articles by this author , and Jonathan ColemanJonathan Coleman More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.220AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Genomic characterization of presurgical biopsy specimens and final pathology of patients with UTUC may allow for thoughtful integration of systemic and targeted therapies. We report the association of genetic profiles with clinicopathologic outcomes in patients with UTUC. METHODS Tumor and germline DNA from patients with UTUC (n=70) were analyzed using a next -generation exon capture sequencing assay to identify somatic mutations and copy number alterations in 300 cancer-associated genes. Fishers test was used to assess the association between altered genes and tumor grade, stage, and organ-confined (OC) status (T3/T4±N+). Kaplan Meier and regression analyses were used for clinical outcomes. RESULTS Pathologic stage was Ta, T1, T2, T3, T4 in 19 (27.5%), 14 (20.3%), 8 (11.6%), 21 (30.4%), and 7 (10.1%) patients, respectively. 17 patients (24.6%) had positive lymph nodes. 29 patients had distant recurrences and 22 patients died from their disease. Of 24 commonly mutated genes within 9 genomic pathways, TP53/MDM2 and FGFR3 were the only two genes uniformly associated with grade, stage, OC status, RFS, and CSS. A risk score was assigned: 0=WT TP53/MDM2 and Mut FGFR3 (n=30), 1=WT TP53/MDM2 and WT (n=19), and 2=Mut TP53/MDM2 and WT FGFR3 (n=17). 3 patients with both Mut TP53/MDM2 and Mut FGFR3 were excluded from risk score analyses. The frequencies of high grade (60 vs 100 vs 100%, p<0.001), advanced stage (16.7 vs 47.4 vs 76.5%, p<0.001), and non-OC disease (20 vs 47.4 vs 76.5%, p<0.001) were greater for risk scores of 0, 1, and 2, respectively. RFS (81%, 44%, and 21%, log-rank p<0.001) and CSS (93%, 71%, and 54% log-rank p=0.008) worsened at 3 years for risk scores 0, 1, and 2, respectively (Figure 1A/1B). Risk score remained significant in multivariable analysis adjusted for concomitant CIS, another factor known preoperatively, for both RFS (HR 2.6, 95% CI 1.6-4.4, p<0.001) and CSS (HR 2.3, 95% CI 1.3-4.3, p=0.007). CONCLUSIONS TP53/MDM2 mutations are associated with adverse clinicopathologic outcomes whereas FGFR3 mutations are associated with favorable outcomes. This information may be combined for enhanced risk stratification, particularly in the biopsy setting. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e68-e69 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Aditya Bagrodia More articles by this author Eugene Cha More articles by this author John Sfakianos More articles by this author Gopa Iyer More articles by this author Byron Lee More articles by this author Sasinya Scott More articles by this author Emily Zabor More articles by this author Ronak Shah More articles by this author Qinghu Ren More articles by this author Philip Kim More articles by this author Ari Hakimi More articles by this author Irina Ostrovnaya More articles by this author Jonathan Rosenberg More articles by this author Guido Dalbagni More articles by this author Dean Bajorin More articles by this author Victor Reuter More articles by this author Michael Berger More articles by this author Bernard Bochner More articles by this author Hikmat Al-Ahmadie More articles by this author David Solit More articles by this author Jonathan Coleman More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...