Metastatic Bladder Cancer: Novel Therapies

Tian Zhang, MD, MHS, FASCO

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How to cite: Zhang T. Metastatic Bladder Cancer: Novel Therapies. Grand Rounds in Urology. December 2025. Accessed Apr 2026. https://grandroundsinurology.com/metastatic-bladder-cancer-novel-therapies/

Summary

Tian Zhang, MD, MHS, FASCO, Director of Clinical Research, Hematology and Oncology, and Associate Professor, Internal Medicine, University of Texas, Dallas, Texas, reviews emerging therapeutic strategies for metastatic bladder cancer, focusing on next-generation antibody-drug conjugates, novel fibroblast growth factor receptor 3 inhibitors, and mechanisms of resistance in the post–enfortumab vedotin plus pembrolizumab era.

She begins by discussing the evolving role of HER2-directed antibody drug conjugates, including disitamab vedotin and trastuzumab deruxtecan, which demonstrate activity in HER2-expressing urothelial carcinoma. Combination strategies with immunotherapy are also highlighted.

Trop-2–directed therapies remain in development despite setbacks in this space. Datopotamab deruxtecan and other agents are under active investigation in refractory disease.

Vepugratinib, a fibroblast growth factor receptor 3–selective inhibitor, shows promising activity with a toxicity profile characterized primarily by grade 1–2 adverse events. A phase 3 triplet study combining vepugratinib with enfortumab vedotin and pembrolizumab is underway.

Additional approaches include bispecific antibodies, bispecific antibody drug conjugates, aryl hydrocarbon receptor inhibition, and personalized neoantigen vaccine platforms.

Dr. Zhang emphasizes the urgent need to understand resistance mechanisms to enfortumab vedotin plus pembrolizumab, including potential downregulation of Nectin-4 or resistance to cytotoxic payloads.

About the 2025 International Bladder Cancer Update Expert Forum™

The International Bladder Cancer Update (IBCU) Expert Forum™ is a physician-led conference bringing together urologists, urologic oncologists, and other healthcare professionals involved in the treatment and diagnosis of bladder cancer. The conference offers interactive expert lectures, panel discussions, and case presentations offers a dynamic look at the latest advancements and state-of-the-art technologies in the field of bladder cancer management. The 2025 IBCU Expert Forum™ encompassed the management of muscle-invasive, non-muscle invasive, and metastatic bladder cancer; upper-tract disease; as well as giving a specific focus on radical vs bladder sparing surgical approaches.

ABOUT THE AUTHOR

Tian Zhang, MD, MHS, FASCO

Tian Zhang, MD, MHS, is the Director of Clinical Research in the Division of Hematology and Oncology and an Associate Professor within the Department of Internal Medicine at the University of Texas at Dallas, and also serves as the Associate Director of Clinical Research for the Simmons Comprehensive Cancer Center at the University of Texas. Dr Zhang specializes in the diagnosis and treatment of genitourinary malignancies, including kidney, prostate, bladder, and testicular cancers. She is an accomplished clinical trialist and translational researcher, with a focus on evaluating clinical development of novel therapeutics and evaluating biomarkers for genitourinary malignancies.

About The Author

Tian Zhang, MD, MHS, FASCO

Tian Zhang, MD, MHS, is the Director of Clinical Research in the Division of Hematology and Oncology and an Associate Professor within the Department of Internal Medicine at the University of Texas at Dallas, and also serves as the Associate Director of Clinical Research for the Simmons Comprehensive Cancer Center at the University of Texas. Dr Zhang specializes in the diagnosis and treatment of genitourinary malignancies, including kidney, prostate, bladder, and testicular cancers. She is an accomplished clinical trialist and translational researcher, with a focus on evaluating clinical development of novel therapeutics and evaluating biomarkers for genitourinary malignancies. Dr. Zhang earned her medical degree from the Harvard-MIT Health Sciences and Technology (HST) program at Harvard Medical School in Cambridge, Massachusetts. She completed a residency in Internal Medicine and a fellowship in Hematology-Oncology at Duke University in Durham, North Carolina. Dr. Zhang earned a Master of Health Sciences in the Clinical Research Training Program, also at Duke University. Dr. Zhang has gained an international reputation for developing clinical trials in kidney, prostate, and bladder cancers. Notably, she serves as the study chair for PDIGREE, an NCI-funded phase III trial in metastatic renal cell carcinoma, and has initiated numerous trials for patients at UT Southwestern. Dr. Zhang is a member of several professional organizations, including the American Society of Clinical Oncology (ASCO), the American Association for Cancer Research (AACR), the European Society for Medical Oncology (ESMO), the Society for Immunotherapy of Cancer (SITC), and the Chinese American Hematology and Oncology Network (CAHON). She serves on numerous committees, including as Co-chair of the National Cancer Institute Genitourinary (GU) Steering Committee Renal Task Force. She is a member of several ASCO and SITC clinical management guidelines committees, as well as the Alliance for Clinical Trials in Oncology GU Oncology and Immuno-Oncology Committees.

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