17 August 2026
: Case report 
A Case Report of a 64-Year-Old Man With Urothelial Carcinoma With Brain and Leptomeningeal Metastases Treated With Intrathecal Methotrexate as Part of Multimodal Management
Unusual or unexpected effect of treatment, Rare disease
Leland F. Damron ABCDEF 1, Leigh Kinney ADEF 1, Nikhita Kathuria-Prakash ADEF 2, Marilena Iliopoulos EF 3, Dimitrios Stefanoudakis EF 4, Lidia P. Lopez BDEF 2, Marah Sakkal
BE 5, Negar Khanlou BCD 6, Steven D. Hart BCD 6, Neda A. Moatamed BCD 6, Nicolaos J. Palaskas AEF 2, Alexandra Drakaki ACDEG 2,4*
DOI: 10.12659/AJCR.951572
Am J Case Rep 2026; 27:e951572
Table 1 Summary of systemic and CNS-directed therapies administered during the patient’s disease course. The table outlines the sequence of treatment lines, indications for therapy, best response, and reason for treatment discontinuation in this patient with metastatic upper tract urothelial carcinoma.
| Treatment line | Regimen | Indication | Best response | Reason for discontinuation |
|---|---|---|---|---|
| Adjuvant | Gemcitabine, cisplatin | Post-nephroureterectomy | Complete response | Completed |
| First-line (metastatic) | Enfortumab vedotin | Pulmonary metastases | Complete response | Peripheral neuropathy |
| Second-line systemic | Pembrolizumab, enfortumab vedotin | CNS-confined metastasis | Progressive disease | Radiographic progression |
| Third-line systemic | Nivolumab, ipilimumab | Progression of CNS disease burden | Progressive disease | Radiographic progression |
| Fourth-line systemic | Sacituzumab govitecan | Progression of CNS disease burden | Progressive disease | Radiographic progression |
| CNS-directed | Intrathecal methotrexate | Leptomeningeal disease | Temporary CSF clearance | CNS progression |
| CNS, central nervous system; CSF, cerebrospinal fluid. | ||||