BACKGROUND
The central nervous system (CNS) is a rare site for upper tract urothelial carcinoma (UTUC) metastasis and typically carries a poor prognosis. Little is known about effective treatments. This report describes a 64-year-old man with UTUC with brain and leptomeningeal metastases. He was treated with multiple lines of chemotherapy, immunotherapy, surgery, radiation, and intrathecal methotrexate as part of multimodal therapy delivered through multidisciplinary care.
CASE REPORT
A 64-year-old man with multiple sclerosis was diagnosed with UTUC. Initial management included a nephroureterectomy followed by platinum-based chemotherapy. Despite this treatment, his malignancy recurred with pulmonary metastases, treated with enfortumab vedotin and local ablation. After this treatment, he achieved systemic disease control. However, he later presented with neurologic symptoms, and imaging showed brain metastases. He underwent resection followed by stereotactic radiation therapy and immunotherapy. Even with this multimodal treatment, he developed leptomeningeal spread, evidenced by cytology-positive cerebrospinal fluid (CSF). Following progression on multiple systemic therapies, he received intrathecal methotrexate with temporary clearance of tumor cells from his CSF before disease progression. This treatment course, including chemotherapy, immunotherapy, and intrathecal methotrexate, prolonged the patient’s life before he unfortunately died from his disease.
CONCLUSIONS
This case report outlines a treatment approach for a rare complication of UTUC. This regimen includes both standard-of-care therapy and inventive strategies extrapolated from data on other solid tumors. Additionally, it contributes to the limited data on the management of CNS metastasis in rare solid tumor malignancies, which could inform future clinical decision-making.

Keywords: Brain Diseases; Case Reports; Immunotherapy; Methotrexate; Neoplasms