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The evolving treatment landscape of metastatic urothelial cancer

Nature Reviews Urology (2024)Cite this article

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Abstract

Cisplatin-based chemotherapy is currently the first-line standard of care for patients with metastatic urothelial cancer (mUC); however, up to 50% of patients are ineligible for cisplatin, necessitating alternative treatment options. Immune checkpoint inhibitors have been shown to be effective in cisplatin-ineligible patients. However, despite advances in the first-line setting, the prognosis remains poor, and challenges persist in selecting optimal therapies, treatment sequences and combination regimens. Maintenance therapy with avelumab revealed improved overall (OS) and progression-free survival (PFS) compared with best supportive care alone in patients with platinum-responsive mUC. Antibody–drug conjugates and targeted therapy with fibroblast growth factor receptor (FGFR) inhibitors have shown promise in selected patients, particularly in patients with metastatic disease that has progressed despite platinum-based chemotherapy. At the European Society of Medical Oncology Congress in 2023, groundbreaking results were presented from two phase III trials, EV-302/KEYNOTE-A39 and CheckMate 901, focusing on previously untreated mUC. In the former, the combination of enfortumab vedotin and pembrolizumab showed significant improvements in OS, PFS and overall response rate compared with chemotherapy alone; the combination of nivolumab with gemcitabine–cisplatin chemotherapy demonstrated a significant extension in median OS, PFS and overall response rate compared with chemotherapy alone. In addition, erdafitinib therapy resulted in significantly longer OS than chemotherapy among patients with mUC and FGFR alterations after previous treatment with immune checkpoint inhibitors. This comprehensive summary of the current treatment landscape for mUC incorporates clinical trial evidence and discussion of agents that are currently under investigation to provide support for clinical decision making and understanding of future therapeutic approaches.

Key points

  • Bladder cancer is the tenth most diagnosed cancer worldwide, affecting about 2.4 per 100,000 women and 9.5 per 100,000 men worldwide per year.

  • Between 5% and 10% of people with urothelial cancer have metastatic disease at diagnosis.

  • Cisplatin-based chemotherapy is currently the standard of care for first-line treatment of mUC, with a median overall survival of about 14 months.

  • Up to 50% of individuals with mUC are ineligible for cisplatin based on the Galsky criteria; carboplatin, gemcitabine and immunotherapeutic agents are alternatives.

  • Immunotherapy, antibody–drug conjugates and targeted agents, such as FGFR inhibitors, have revolutionized the mUC treatment landscape.

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Fig. 1: Timeline of approved drugs for metastatic urothelial carcinoma.
Fig. 2: Type and mechanism of drug classes used in the treatment landscape of metastatic urothelial carcinoma.
Fig. 3: Current and future management of patients with metastatic urothelial carcinoma.

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Authors and Affiliations

  1. Department of Health Sciences, University of Florence, Florence, Italy

    Giandomenico Roviello & Martina Catalano

  2. Oncology Unit, Macerata Hospital, Macerata, Italy

    Matteo Santoni

  3. Dana-Farber Cancer Institute, Boston, MA, USA

    Guru P. Sonpavde

  4. University of Central Florida, Orlando, FL, USA

    Guru P. Sonpavde

  5. AdventHealth Cancer Institute, Orlando, FL, USA

    Guru P. Sonpavde

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Roviello, G., Santoni, M., Sonpavde, G.P. et al. The evolving treatment landscape of metastatic urothelial cancer. Nat Rev Urol (2024). https://doi.org/10.1038/s41585-024-00872-0

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