PATH-53. Clinical and molecular features associated with poor outcomes following surgical resection of brain metastases from urinary tract cancers

INTRODUCTION Brain metastases originating from the urinary tract are rare yet associated with significant morbidity and mortality. Neurosurgical outcomes and molecular characteristics in this patient population remain poorly defined. OBJECTIVE To evaluate overall survival, local central nervous system (CNS) progression, distant CNS recurrence, postoperative leptomeningeal disease (LMD) rates, and molecular alterations in adult patients with resected brain metastases from bladder cancer. METHODS This was a retrospective study of 20 consecutive adult patients (17 urothelial carcinoma, 1 urachal adenocarcinoma, 1 urothelial adenocarcinoma, 1 urothelial small cell neuroendocrine carcinoma) identified in a single-institution registry who underwent resection of a brain metastasis. Targeted DNA sequencing results were reported when obtained as part of routine clinical practice. Time-to-event clinical outcomes were analyzed using Kaplan–Meier curves and Cox proportional hazards regression models. RESULTS Mean age was 66.9 years. 75% were male. Median overall survival from surgery was 6.8 months with median local and distant CNS progression times of 16.1 and 10.3 months, respectively. Postoperative LMD occurred in 4 patients (20%), and the median time to LMD was not reached. DNA sequencing (n=6) demonstrated a tumor mutational burden of 11.6 (6.4) mutations/MB and recurrent alterations in TP53 (n=4, 67%), NF1 (n=3, 50%), TERT (n=3, 50%), or CDKN2A/B (n=2, 33%). In a multivariable Cox proportional Hazards model, postoperative radiotherapy (HR=0.004, 95% CI=0.000-0.277, p=0.011), and tumor volume (HR=1.13, 95% CI=1.02-1.26, p=0.021) were significantly associated with overall survival. Patients with CDKN2A/B homozygous deletion had significantly lower overall survival (median, 3.45 vs. 6.77 months, p=0.027), LMD-free survival (median, 4.47 months vs. not reached, p=0.046), and distant CNS recurrence-free survival (median, 3.13 vs. 10.33 months, p=0.046). CONCLUSION In patients with primary bladder cancers, larger brain metastasis volume may correlate with worse survival, while CDKN2A/B homozygous deletion is associated with worse prognoses for overall survival, LMD, and distant CNS recurrence.