Presentation Authors: Sarah Garnier, Julie Vendrell, Montpellier, France, Bernard Boillot, Grenoble, France, Gilles Karsenty, Jean Michel Guys, Marseille, France, Laurent Soustelle, Nimes, France, Thomas Blanc, Veronique Phe, Paris, France, Alexia Even, Garches, France, Emmanuel Chartier Kasler, Paris, France, Pierre Costas, Nimes, France, François Iborra, Montpellier, France, Ourdia Bouali, Xavier Gamé, Toulouse, France, Jerome Solassol, Nicolas Kalfa*, montpellier, France
Introduction: The aim of this study is to describe the natural history, the prognosis and the molecular analysis of a panel of cancer genes on a large series of patients with malignancy after augmentation enterocystoplasty (AE).
Methods: A multicenter nationwide retrospective study included 16 patients based on operative, oncologic and anatomopathological reports. 11 tumor samples were analyzed using an amplicon-based Next Generation Sequencing assay specifically dedicated to the detection of clinically actionable somatic alterations of 21 relevant cancer genes.
Results: AE were performed for congenital neurogenic bladders (50%) and bladder exstrophies (25%) mainly. The average age at AE was 16.5-years-old. Ileum (44%), stomach (31%), colon (19%) and ileo-colon (6%) were used for AE. The mean latency period was 20 years (5-45). Clinical manifestations, mainly hematuria, were the main circumstance of diagnosis (88%). Three patients underwent systematic endoscopy but only one was diagnosed this way. Histology showed adenocarcinomas (44%), urothelial-cell (31%), squamous-cell (19%) and undifferentiated (6%) carcinomas. 80% of gastrocystoplasties led to adenocarcinomas while urothelial-cell carcinoma was typically found after colocystoplasties. Malignancies were mainly on the bowel segment (56%) and the native bladder (43%). 75% of patients presented with an advanced stage of the disease (lymph nodes involvement: n=9 and/or distant metastasis: n=7). Urinary tract infections were statistically associated with initial metastatic status (p=0,02) but lithiasis, intermittent catheterism, immunosuppression and tumor localization were not. The 1-year overall survival rate was 50%. Only 3 patients are disease-free with a median follow-up of 70 months (10-89). Over half of analyzable samples (n=5/9) harbored missense mutations in known oncodriver genes. Two samples exhibited mutations in KIT and PDGFRA and one sample in KRAS hotspot. Two samples showed an alteration in the exon 3 of CTNNB1. One tumor that harbored a CTNNB1 mutation, also exhibits a concomitant ERBB4 alteration.
Conclusions: Malignancy after AE is lately diagnosed with frequent metastases and a very low 1-year survival rate. Systematic endoscopy is not widely used and its efficiency may be limited. We report for the first time in these tumors mutations of cancer genes for witch target therapies are available or under development.