Characterization of brain metastases in urothelial cancers

Abstract Brain metastases are rarely observed in urothelial cancers but confer a uniformly poor prognosis. We sought to evaluate the clinical characteristics and course of brain metastases in four patients with primary urothelial cancer with secondary molecular brain tumor characterization available in 3 patients. Mean age was 68 years. Three of the patients were men. Two patients had both primary upper tract and bladder urothelial cancers, and two had bladder cancer alone. Three patients had initial nephroureterectomy and/or radical cystectomy, with subsequent development of initial distant metastasis at a median of 7.9 months. All four patients received platinum-based systemic therapy following initial metastasis. Median onset of brain metastasis from initial distant metastasis was 11.5 months. Median overall survival (OS) from the diagnosis of brain metastasis was 6 months (range: 3.1 – 12.8 months). Three patients who had comprehensive somatic tumor profiling of the brain metastasis using the Oncomine® panel showed mutations in the APC, TP53, and FGFR3 genes, loss of function in TP53 and BRCA-2, and deletion of MHS2. Our findings suggest brain metastases is a uniformly fatal diagnosis and a need for future exploration of primary tumor and metastatic sequencing in order to better define the role of current therapies for metastatic brain urothelial cancers which remains an area of increased unmet need.