---
title: "Intrathecal Methotrexate for Leptomeningeal Metastases in Urothelial Carcinoma: Case Report"
id: "pubmed-42607018"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42607018"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42607018/"
doi: "10.12659/AJCR.951572"
published_at: "2026-08-17T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Intrathecal Methotrexate for Leptomeningeal Metastases in Urothelial Carcinoma: Case Report
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42607018
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42607018/)
- **DOI:** [10.12659/AJCR.951572](https://doi.org/10.12659%2FAJCR.951572)
- **Published At:** 2026-08-17T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- A 64-year-old man with a history of multiple sclerosis was diagnosed with **upper tract urothelial carcinoma (UTUC)** and initially treated with nephroureterectomy followed by platinum-based chemotherapy. - The patient developed systemic recurrence with pulmonary metastases that were treated with **enfortumab vedotin** and local ablation, achieving systemic disease control for a period. - He later presented with neurologic symptoms and was found to have **brain metastases**; management included surgical resection, stereotactic radiation therapy, and immunotherapy. - Despite multimodal CNS-directed therapy, he progressed to **leptomeningeal metastases**, confirmed by cytology-positive cerebrospinal fluid (CSF). - After progression on multiple systemic therapies, the patient received **intrathecal methotrexate**, which produced a temporary clearance of tumor cells from CSF before subsequent disease progression. - The multimodal approach—surgery, radiation, systemic chemotherapy and immunotherapy, and intrathecal methotrexate—prolonged the patient’s life, though he ultimately died from his disease. - The case illustrates a rare clinical course for UTUC with CNS involvement and contributes limited observational data on using intrathecal chemotherapy in solid-tumor leptomeningeal disease. - Specific details such as intrathecal methotrexate dosing, schedule, number of administrations, adverse events, timelines, and exact survival duration were not reported in the abstract and therefore are not available from this source. - The authors framed their approach as combining standard-of-care therapies and strategies extrapolated from other solid tumors; this case may inform multidisciplinary decision-making in similar rare presentations.
## Clinical Analysis & Structured Key Points
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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 [Leland F Damron](https://pubmed.ncbi.nlm.nih.gov/?term=Damron+LF&cauthor_id=42607018)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#full-view-affiliation-1 "Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Leigh Kinney](https://pubmed.ncbi.nlm.nih.gov/?term=Kinney+L&cauthor_id=42607018)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#full-view-affiliation-1 "Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Nikhita Kathuria-Prakash](https://pubmed.ncbi.nlm.nih.gov/?term=Kathuria-Prakash+N&cauthor_id=42607018)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#full-view-affiliation-2 "Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Marilena Iliopoulos](https://pubmed.ncbi.nlm.nih.gov/?term=Iliopoulos+M&cauthor_id=42607018)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#full-view-affiliation-3 "Marymount High School, Los Angeles, CA, USA."), [Dimitrios Stefanoudakis](https://pubmed.ncbi.nlm.nih.gov/?term=Stefanoudakis+D&cauthor_id=42607018)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#full-view-affiliation-4 "Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Lidia P Lopez](https://pubmed.ncbi.nlm.nih.gov/?term=Lopez+LP&cauthor_id=42607018)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#full-view-affiliation-2 "Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Marah Sakkal](https://pubmed.ncbi.nlm.nih.gov/?term=Sakkal+M&cauthor_id=42607018)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#full-view-affiliation-5 "Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Negar Khanlou](https://pubmed.ncbi.nlm.nih.gov/?term=Khanlou+N&cauthor_id=42607018)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#full-view-affiliation-6 "Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Steven D Hart](https://pubmed.ncbi.nlm.nih.gov/?term=Hart+SD&cauthor_id=42607018)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#full-view-affiliation-6 "Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Neda A Moatamed](https://pubmed.ncbi.nlm.nih.gov/?term=Moatamed+NA&cauthor_id=42607018)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#full-view-affiliation-6 "Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Nicolaos J Palaskas](https://pubmed.ncbi.nlm.nih.gov/?term=Palaskas+NJ&cauthor_id=42607018)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#full-view-affiliation-2 "Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Alexandra Drakaki](https://pubmed.ncbi.nlm.nih.gov/?term=Drakaki+A&cauthor_id=42607018)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#full-view-affiliation-2 "Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#full-view-affiliation-4 "Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.") Affiliations Expand ### Affiliations * 1 Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. * 2 Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. * 3 Marymount High School, Los Angeles, CA, USA. * 4 Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. * 5 Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. * 6 Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. * PMID: **42607018** * DOI: [ 10.12659/AJCR.951572 ](https://doi.org/10.12659/ajcr.951572) Item in Clipboard Case Reports # 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 Leland F Damron et al. Am J Case Rep. 2026. Show details Display options Display options Format Abstract PubMed PMID Am J Case Rep Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Am+J+Case+Rep%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Am+J+Case+Rep%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42607018/) . 2026 Aug 17:27:e951572. doi: 10.12659/AJCR.951572. ### Authors [Leland F Damron](https://pubmed.ncbi.nlm.nih.gov/?term=Damron+LF&cauthor_id=42607018)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#short-view-affiliation-1 "Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Leigh Kinney](https://pubmed.ncbi.nlm.nih.gov/?term=Kinney+L&cauthor_id=42607018)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#short-view-affiliation-1 "Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Nikhita Kathuria-Prakash](https://pubmed.ncbi.nlm.nih.gov/?term=Kathuria-Prakash+N&cauthor_id=42607018)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#short-view-affiliation-2 "Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Marilena Iliopoulos](https://pubmed.ncbi.nlm.nih.gov/?term=Iliopoulos+M&cauthor_id=42607018)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#short-view-affiliation-3 "Marymount High School, Los Angeles, CA, USA."), [Dimitrios Stefanoudakis](https://pubmed.ncbi.nlm.nih.gov/?term=Stefanoudakis+D&cauthor_id=42607018)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#short-view-affiliation-4 "Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Lidia P Lopez](https://pubmed.ncbi.nlm.nih.gov/?term=Lopez+LP&cauthor_id=42607018)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#short-view-affiliation-2 "Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Marah Sakkal](https://pubmed.ncbi.nlm.nih.gov/?term=Sakkal+M&cauthor_id=42607018)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#short-view-affiliation-5 "Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Negar Khanlou](https://pubmed.ncbi.nlm.nih.gov/?term=Khanlou+N&cauthor_id=42607018)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#short-view-affiliation-6 "Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Steven D Hart](https://pubmed.ncbi.nlm.nih.gov/?term=Hart+SD&cauthor_id=42607018)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#short-view-affiliation-6 "Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Neda A Moatamed](https://pubmed.ncbi.nlm.nih.gov/?term=Moatamed+NA&cauthor_id=42607018)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#short-view-affiliation-6 "Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Nicolaos J Palaskas](https://pubmed.ncbi.nlm.nih.gov/?term=Palaskas+NJ&cauthor_id=42607018)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#short-view-affiliation-2 "Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA."), [Alexandra Drakaki](https://pubmed.ncbi.nlm.nih.gov/?term=Drakaki+A&cauthor_id=42607018)[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#short-view-affiliation-2 "Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.")[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42607018/#short-view-affiliation-4 "Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.") ### Affiliations * 1 Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. * 2 Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. * 3 Marymount High School, Los Angeles, CA, USA. * 4 Department of Urology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. * 5 Department of Radiology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. * 6 Department of Pathology, David Geffen School of Medicine, University of California, Los Angeles, CA, USA. * PMID: **42607018** * DOI: [ 10.12659/AJCR.951572 ](https://doi.org/10.12659/ajcr.951572) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract 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. 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