Abstract
e16030 Background: Programmed cell death (PD)-1 / PD-ligand 1 (PD-L1) inhibitors have made a breakthrough mainly in the treatment of PD-L1 positive advanced urothelial bladder cancer (UBC). The effect of Fibroblast Growth Factor Receptor 3 (FGFR3) mutation on the treatment outcomes of PD-L1 treatment still remains unclear. Our goal was to assess the frequency of FGFR mutations in different tumor stages, in relation with PD-L1 status. Methods: Enrolled patients were diagnosed with UBC and underwent radical cystectomy between 2006-2016 at the University of Szeged, Hungary. FGFR3 mutation analysis by targeted next-generation sequencing and PD-L1 (28-8 DAKOR and SP142 VentanaR) tests were carried out from the most infiltrative area of tumors, in T0 cases from the earlier resection samples. The treatment and survival data were collected from the National Health Insurance Fund (NHIF), Hungary. Independence between covariates was tested using chi-square tests, survival analysis was performed using Kaplan-Meier models and Cox proportional hazards regression. Results: 215 of all 310 UBC samples (T0:19 (8.8%); superficial 43(20%); muscle invasive 41(19%); extraorgan 112 (52%)) could be tested for both PD-L1 and FGFR successfully. Pairwise dependency between tumor stage, FGFR3 mutation status and PD-L1 expression were all found to be significant (p < 0.01). In cases of less advanced diseases FGFR mutation was more often detected. We have found that FGFR mutated samples are less likely to be PD-L1 positive than wild type ones. The effect of all covariates on survival was found to be in accordance with the effect of tumor stage. Conclusions: FGFR alteration frequency varied with stage of disease, with higher positivity rates in early stages, but that lower PD-L1 expression was observed in FGFR mutant patients across disease stages.
Published Version
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