State of the art of adjuvant immunotherapy in urothelial cancer: New developments and upcoming changes

Hum Vaccin Immunother. 2025 Dec;21(1):2440165. doi: 10.1080/21645515.2024.2440165. Epub 2024 Dec 19.

Abstract

In recent years, several clinical trials focused on the potential role of immune-checkpoint inhibitors (ICIs) in the adjuvant treatment of muscle-invasive urothelial cancer (UC). Heretofore, only the anti-programmed death protein 1 (anti-PD1) nivolumab received European Medical Agency (EMA) approval for cisplatin-unfit patients. In our work, we deeply analyzed the results of the three pivotal studies in view of the rapidly evolving therapeutic advanced UC's scenario. Furthermore, there are several ongoing research to investigate ICIs and other emerging immune agents in this setting; results are awaited. Additionally, current efforts have been made to assess the role of these agents in earlier disease settings, particularly in high-risk non-muscle-invasive bladder cancer (NMIBC). In our review, we analyzed the potential role of predictive and/or prognostic biomarkers that may improve patient selection and treatment efficacy. To conclude, we highlighted the upcoming changes that could redefine the standard of care for patients with early-stage UC.

Keywords: Urothelial cancer; adjuvant therapy; biomarkers; bladder cancer; immunotherapy; muscle-invasive bladder cancer; non-muscle invasive bladder cancer.

Plain language summary

This review discusses the latest advancements in post-surgery immune treatments given to prevent recurrences from urothelial cancer. Urothelial cancer is the most frequent type of tumor that affects the bladder and the upper parts of the urinary tract. Immunotherapy is a treatment that helps the body’s immune system to fight cancer cells more effectively. Unlike other treatments – such as chemotherapy – that directly kills tumor cells, immunotherapy boosts the natural defenses of the body to attack the cancer. Our article provides a summary of the current state of adjuvant immunotherapy, with the most recent progress and the ongoing clinical trials based on immune checkpoint inhibitors (ICIs). These agents help the immune defenses to recognize and attack cancer cells by blocking specific proteins that prevent the immune system from working properly. Additionally, the review analyzes the innovative drugs that are being developed for earlier stages of the disease, especially for non-muscle-invasive bladder cancer (NMIBC), a type of tumor that has not spread into the muscle layer of the bladder wall. Furthermore, our work also examines potential biological indicators, known as biomarkers that can help clinicians to identify which patients are most likely to benefit from specific treatments, making therapies more effective and personalized. Finally, the article looks at how ongoing research and recent approval of new treatments could lead to significant changes in clinical practice, potentially setting up new standards for treating patients with early-stage urothelial cancer.

Publication types

  • Review

MeSH terms

  • Chemotherapy, Adjuvant / methods
  • Humans
  • Immune Checkpoint Inhibitors* / therapeutic use
  • Immunotherapy* / methods
  • Nivolumab / therapeutic use
  • Treatment Outcome
  • Urinary Bladder Neoplasms* / drug therapy
  • Urinary Bladder Neoplasms* / immunology
  • Urinary Bladder Neoplasms* / therapy

Substances

  • Immune Checkpoint Inhibitors
  • Nivolumab