The Prognostic Value of FGFR3 Expression in Patients with T1 Non-Muscle Invasive Bladder Cancer

Purpose: Fibroblast growth factor receptor 3 (FGFR3) alterations are frequent in non-muscle-invasive bladder cancer (NMIBC), although current data regarding the prognostic and therapeutic relevance are inconsistent. We analyzed the prognostic role of FGFR3 mRNA expression in stage T1 NMIBC.

Patients And Methods: The mRNA expression of FGFR3 and cyclin-dependent kinase inhibitor 2A (CDKN2A) was measured by RT-qPCR in 80 patients with stage T1 NMIBC treated with transurethral resection of the bladder and correlated with clinical data and KRT5 and KRT20 expression, used as surrogate markers for basal and luminal subtypes, respectively.

Results: FGFR3 and CDKN2A transcript levels were not correlated. FGFR3 expression was associated with the expression of KRT5 (p=0.002) and KRT20 (p < 0.001). CDKN2A expression was negatively correlated with KRT5 (p=0.030). In Kaplan-Meier analysis and univariable Cox regression analysis, high FGFR3 expression was associated with significantly reduced recurrence-free survival (RFS) (HR=3.78; p < 0.001) and improved overall survival (OS) (HR=0.50; p=0.043), while high CDKN2A expression was associated with reduced OS (HR=2.34; p=0.034). Patient age was the only clinicopathological parameter associated with reduced OS (HR=2.29; p=0.022). No parameter was an independent prognostic factor in multivariable analysis. Next, we stratified the patients depending on their lineage differentiation. In univariable analysis, the prognostic effect of FGFR3 and CDKN2A was observed primarily in patients demonstrating high expression of KRT5 or KRT20, whereas high FGFR3 expression was associated with significantly reduced RFS, irrespective of instillation therapy.

Conclusion: Stage T1 NMIBC patients with high FGFR3 expression show shorter RFS but better OS than patients with low FGFR3 expression.