MP7-12 DETECTION OF FGFR3 MUTATIONS FROM URINE SEDIMENT DNA TO PREDICT THE RISK OF INTRAVESICAL RECURRENCE AFTER RADICAL NEPHROURETERECTOMY FOR UPPER TRACT UROTHELIAL CARCINOMA

You have accessJournal of UrologyBladder Cancer: Upper Tract TCC II1 Apr 2015MP7-12 DETECTION OF FGFR3 MUTATIONS FROM URINE SEDIMENT DNA TO PREDICT THE RISK OF INTRAVESICAL RECURRENCE AFTER RADICAL NEPHROURETERECTOMY FOR UPPER TRACT UROTHELIAL CARCINOMA Thomas Seisen, Morgan Rouprêt, Géraldine Cancel-Tassin, Priscilla Léon, Eva Compérat, Sarah Drouin, Véronique Phé, Raphaële Renard-Penna, Pierre Mozer, and Olivier Cussenot Thomas SeisenThomas Seisen More articles by this author , Morgan RouprêtMorgan Rouprêt More articles by this author , Géraldine Cancel-TassinGéraldine Cancel-Tassin More articles by this author , Priscilla LéonPriscilla Léon More articles by this author , Eva CompératEva Compérat More articles by this author , Sarah DrouinSarah Drouin More articles by this author , Véronique PhéVéronique Phé More articles by this author , Raphaële Renard-PennaRaphaële Renard-Penna More articles by this author , Pierre MozerPierre Mozer More articles by this author , and Olivier CussenotOlivier Cussenot More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.219AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES To assess the role of FGFR3 mutations, detected from urine sediment DNA, in intravesical recurrence (IVR) after radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC). METHODS Freshly voided urine samples were obtained from 46 patients before undergoing RNU to treat UTUC. DNA was extracted from urine sediments to perform allele-specific PCR assays for the detection of R248C, S249C, G372C and Y375C mutations. Kaplan Meier method and log-rank test have been used to analyze IVR-free survival according to FGFR-3 status. Univariate and multivariate Cox regression analyses have been conducted to determine predictors of IVR. RESULTS Overall, FGFR3 mutations occurred in 21 (46%) patients. The mutation in codon 249 was the most frequent (13/61%), followed by Y375C (4/19%), R248C (2/10%) and G372C (2/10%). Patients with FGFR3 mutations were more likely to develop ureteral (57% vs 40%; p=0.04) superficial (81% vs 52%; p=0.04), low-grade (67% vs 8%; p<0.001) tumors without concomitant CIS (10% vs 40%; p<0.001) or lymphovascular invasion (5% vs 60% ; p<0.001). An IVR was diagnosed in 13 (28%) patients within a median time of 19.9 [15-27] months. The incidence of IVR was significantly greater in patients with FGFR3 mutations (43% vs 16%; p=0,04). The five-years IVR-free survival rates were 52% and 82% in wild type and mutant patients, respectively (p=0,12). In multivariate analysis, current smocker status (HR=2.42; p=0.006), previous bladder cancer (HR=2.14; p<0.001), positive pre-operative urinary cytology (HR=2.25; p<0.001), ureteral tumor location (HR=1.55; p=0.002), multifocality (HR=2.69; p<0.001), invasive pT stage (HR=1.78; p=0.004) were significantly correlated to IVR. However, FGFR3 mutations were not an independent predictor of IVR (HR=2,39; p=0,09). CONCLUSIONS We found clinical evidence that supported the general idea that both the intra-luminal seeding of a single transformed cell and the pan-urothelial field defect mechanisms are deeply involved with IVR after RNU. Furthermore, although FGFR3 mutations were not an independent predictor of IVR, there was an increased risk for developing a bladder cancer after RNU in FGFR3 mutant patients. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e68 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Thomas Seisen More articles by this author Morgan Rouprêt More articles by this author Géraldine Cancel-Tassin More articles by this author Priscilla Léon More articles by this author Eva Compérat More articles by this author Sarah Drouin More articles by this author Véronique Phé More articles by this author Raphaële Renard-Penna More articles by this author Pierre Mozer More articles by this author Olivier Cussenot More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...