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The changing landscape of urothelial carcinoma: on the edge of a paradigm shift
Joshua J. Meeks
Joshua J. Meeks
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Review

The changing landscape of urothelial carcinoma: on the edge of a paradigm shift

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Abstract

Urothelial cancers of the urinary tract are the fourth most common malignancy in men, with a shifting demographic affecting younger patients and an increasing incidence in females. In this Review, we discuss recent discoveries and paradigm-shifting clinical trials that impact all stages of urothelial cancer. New therapeutics and drug-delivery devices have led to multiple approvals for treatments of non-muscle invasive bladder cancer. The addition of chemotherapy, immunotherapy, and antibody-drug conjugates is transforming perioperative treatment for patients with muscle-invasive bladder cancer. The use of liquid biomarkers, circulating tumor DNA, and urinary tumor DNA is aiding the identification of patients at risk for local recurrence and possibly those who can avoid systemic therapy. Finally, integrating biomarkers and systemic treatments is creating a paradigm that could lead to the successful treatment of bladder cancer without requiring bladder removal. Overall, these advancements in biomarkers and novel therapeutics are likely to dramatically improve survival for bladder cancer.

Authors

Joshua J. Meeks

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Figure 1

Novel therapies for early-stage bladder cancer.

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Novel therapies for early-stage bladder cancer.
Multiple new therapeutic...
Multiple new therapeutic strategies are in development for the treatment of non–muscle-invasive bladder cancer. To initiate anticancer immune responses, viral therapies have been developed to drive expression of cytokines, including IFN-α and GM-CSF. Coiled bi-oval devices have been designed to enable sustained, local delivery of chemotherapy. In addition, immunotherapies, including checkpoint inhibitors, are being explored for their potential in bladder cancer, delivered either systemically or locally.

Copyright © 2026 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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