Clinical and Molecular Features Associated with Outcomes Following Surgical Resection of Brain Metastases from Urinary Tract Cancers

Brain metastases originating from primary urinary tract cancers are rare, and neurosurgical outcomes and molecular characteristics remain poorly defined. This study evaluated overall survival (OS), local central nervous system (CNS) progression, distant CNS recurrence, postoperative leptomeningeal disease (LMD) rates, and molecular alterations in bladder cancer brain metastases. A retrospective analysis was performed on 20 patients (17 urothelial carcinoma, 1 urachal adenocarcinoma, 1 urothelial adenocarcinoma, 1 urothelial small cell neuroendocrine carcinoma) who underwent resection of a single brain metastasis. Mean age was 67 years. 75% were male. Median postoperative OS was 6.8 months. Postoperative local progression occurred in 4 (20%), distant progression in 8 (40%), and LMD in 4 (20%) patients. 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%), and CDKN2A/B (n=3, 50%). In a multivariable Cox proportional Hazards model, postoperative radiotherapy (HR=0.0415, p=0.009) was associated with longer OS in this cohort, while larger tumor volume (HR=1.109, p=0.034) was associated with worse OS. Patients with CDKN2A/B homozygous deletions had lower distant CNS recurrence-free survival (median, 4.33 vs. 10.33 months, p=0.046). OS (p=0.2), LMD-free survival (p=0.2), and local CNS progression-free survival (p=0.3) did not differ by CDKN2A/B homozygous deletion status. In urinary tract cancer patients, larger brain metastasis volume was associated with worse survival, while CDKN2A/B homozygous deletion was associated with poorer distant CNS control, though findings are exploratory and require validation in larger cohorts.