Central nervous system involvement is an uncommon but serious complication of upper tract urothelial carcinoma (UTUC) and typically carries a poor prognosis. Effective treatment strategies for brain and leptomeningeal spread from UTUC are not well defined. This case report describes a multimodal management approach used for a 64-year-old man who developed both brain and leptomeningeal metastases from UTUC, highlighting the use of intrathecal methotrexate as part of palliative and disease-directed care.
The patient, a 64-year-old man with preexisting multiple sclerosis, underwent standard surgical management for UTUC with a nephroureterectomy. Postoperative systemic therapy included platinum-based chemotherapy. Despite initial definitive local therapy and adjuvant or first-line chemotherapy, the patient later experienced disease recurrence.
Following recurrence with pulmonary metastases, the patient received treatment with enfortumab vedotin combined with local ablation of metastatic lesions. This regimen achieved systemic disease control for a period, according to the case report abstract. Details on treatment timelines, response assessments, and duration of control were not reported in the abstract.
The patient subsequently developed neurologic symptoms that prompted neuroimaging and revealed brain metastases. Management included surgical resection of intracranial lesions followed by stereotactic radiation therapy. Systemic immunotherapy was also administered in parallel as part of the multimodal strategy. The abstract does not provide specific operative findings, radiation dose/fractionation, immunotherapy agent or schedule, or neurofunctional outcomes beyond the general treatment sequence.
Despite prior local and systemic interventions, the patient progressed to leptomeningeal disease. Diagnosis was established by cytology-positive cerebrospinal fluid (CSF), confirming tumor involvement of the leptomeninges. The report emphasizes that leptomeningeal spread occurred after progression on multiple systemic therapies. Additional diagnostic details such as CSF cell counts, protein, glucose, or neuroimaging findings specific to leptomeningeal disease were not provided in the abstract.
After exhaustion of several systemic treatment options, the treating team administered intrathecal methotrexate as part of the patient’s multimodal care. The intervention produced a temporary clearance of tumor cells from the CSF, as evidenced by subsequent cytologic testing. The abstract does not specify the intrathecal methotrexate dose, frequency, route (e.g., lumbar puncture vs Ommaya reservoir), number of doses, concurrent supportive measures (such as leucovorin), or procedure-related complications. The cytologic clearance was transient, and the patient later experienced disease progression in the CNS.
The sequence of therapies—including surgery, stereotactic radiation, systemic chemotherapy, immunotherapy, and intrathecal methotrexate—contributed to a period of disease control and prolonged survival relative to what might be expected for leptomeningeal dissemination from UTUC. Ultimately, the patient died from his disease. Specific survival intervals from diagnosis of brain metastases or leptomeningeal disease to death are not reported in the abstract.
This case adds to the sparse literature on CNS metastases from UTUC and illustrates a multimodal, multidisciplinary approach that combined standard-of-care systemic treatments with CNS-directed interventions and intrathecal chemotherapy. The temporary CSF cytologic response to intrathecal methotrexate suggests that intrathecal antimetabolite therapy can have biologic activity in leptomeningeal dissemination from urothelial carcinoma, though the clinical benefit was limited and not durable in this case.
The report deliberately extrapolates certain management principles from experience with leptomeningeal disease in other solid tumors, given the absence of robust UTUC-specific data. Important limitations include the lack of detailed reporting in the abstract on dosing, schedules, adverse events, neurologic functional outcomes, and precise survival times; these data were not available from the source abstract.
In a patient with UTUC who developed brain and leptomeningeal metastases, a multidisciplinary multimodal approach that included surgical resection, stereotactic radiation, systemic therapies, and intrathecal methotrexate produced temporary CSF cytologic clearance and a period of disease control before eventual progression and death. This single-case observation contributes limited evidence to inform decision-making in rare presentations of UTUC with CNS involvement and highlights the need for more detailed data on intrathecal chemotherapy use, dosing, complications, and clinical benefit in this setting.
The abstract does not report key treatment details required to assess reproducibility or safety fully: intrathecal methotrexate dose and schedule, route of administration, total number of intrathecal treatments, local and systemic adverse events, timing relative to other therapies, and quantitative survival intervals. These details were not reported in the source abstract and therefore cannot be provided here.
For rare cases of UTUC with CNS involvement, consider multidisciplinary evaluation including neurosurgery, radiation oncology, medical oncology, and neurology. Intrathecal antimetabolite therapy such as intrathecal methotrexate may produce temporary cytologic responses in CSF, but evidence of durable clinical benefit in UTUC leptomeningeal disease is limited and should be weighed against procedural risks and patient goals of care. Further case series or registries are needed to better define efficacy, safety, and optimal administration parameters for intrathecal therapy in this population.