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Salvage systemic therapy for metastatic urothelial carcinoma: an unmet clinical need
Kamaneh Montazeri1, Guru Sonpavde2
1Massachusetts General Hospital, Harvard Medical School, Boston, USA.
Introduction:
Metastatic urothelial carcinoma (mUC) remains a fatal malignancy, despite the recent addition of immune check point inhibitors (ICIs), an FGFR inhibitor and an antibody-drug conjugate (ADC) to the therapeutic armamentarium. The survival rates are particularly dismal after first-line treatment failure, entailing an urgent need for more effective therapies. Advances in understanding biomarkers and identifying targetable molecules have broadened the pathways under investigation in mUC.
Areas Covered:
This review summarizes mUC salvage therapy options, including chemotherapy, ICI, and novel promising agents, including targeted therapies, ADCs, cytotoxic agents and vaccines. For the literature review, a PubMed search and relevant data presented at international conferences were used.
Expert Opinion:
The approval of ICIs, FGFR inhibitor erdafitinib and ADC enfortumab vedotin in the salvage setting has transformed the mUC landscape. Yet there are additional promising agents currently under study. Toxicities are observed with ADCs and FGFR inhibitors, but appear manageable in most patients. The molecular heterogeneity and complex tumor biology are challenging barriers for progress in the therapy of mUC. Advances in molecular profiling, defining validated predictive markers, rational combinations of agents and therapeutically actionable targets will help develop personalized compounds with higher efficacy and less toxicity with hopes to improve outcomes for mUC.
Insights
Metastatic urothelial carcinoma (mUC) treatment needs improvement, especially after initial therapy failure. Novel agents like antibody-drug conjugates (ADCs) and immune checkpoint inhibitors (ICIs) offer new hope for patients with this fatal cancer.
Area of Science:
- Oncology
- Urothelial Carcinoma Research
- Cancer Therapeutics
Background:
- Metastatic urothelial carcinoma (mUC) has a poor prognosis, particularly after first-line treatment failure.
- Current treatments including immune checkpoint inhibitors (ICIs), FGFR inhibitors, and antibody-drug conjugates (ADCs) have improved outcomes but challenges remain.
- Understanding molecular biomarkers and targetable pathways is crucial for advancing mUC therapy.
Purpose of the Study:
- To review current and emerging salvage therapy options for metastatic urothelial carcinoma (mUC).
- To discuss the impact of recent approvals and ongoing investigations in mUC treatment.
- To highlight challenges and future directions in mUC therapy.
Main Methods:
- Comprehensive literature review of PubMed.
- Inclusion of relevant data presented at international oncology conferences.
- Focus on chemotherapy, ICIs, targeted therapies, ADCs, cytotoxic agents, and vaccines for mUC salvage.
Main Results:
- Immune checkpoint inhibitors (ICIs), erdafitinib (FGFR inhibitor), and enfortumab vedotin (ADC) have transformed the salvage setting for mUC.
- Additional promising agents are under investigation, with observed toxicities generally manageable.
- Molecular heterogeneity and complex tumor biology present significant challenges in mUC treatment.
Conclusions:
- Advances in molecular profiling and biomarker identification are essential for developing personalized mUC therapies.
- Rational combinations of agents and identification of actionable targets are key to improving efficacy and reducing toxicity.
- Future progress relies on a deeper understanding of mUC biology to enhance patient outcomes.
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