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Review Article Open Access
Volume 3 | Issue 2 | DOI: https://doi.org/10.33696/cancerimmunol.3.047

Immune Checkpoint Inhibitors in the Management of Urothelial Carcinoma

  • 1Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA
  • 2Section of Urologic Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA
  • 3Division of Medical Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ 08903, USA
  • #Equal author contribution
+ Affiliations - Affiliations

Corresponding Author

Eric A. Singer, eric.singer@rutgers.edu

Received Date: November 23, 2020

Accepted Date: March 24, 2021

Abstract

Urothelial carcinoma is one of the most common cancers in the United States, yet outcomes are historically suboptimal. Since 2016, the approval of five programmed cell death 1 and programmed death-ligand 1 immune checkpoint inhibitors for locally advanced and metastatic urothelial carcinoma has led to improved oncologic outcomes for many patients in the second-line setting. Two checkpoint inhibitors, pembrolizumab and atezolizumab subsequently earned approval for first-line therapy with restricted indications. More recently, pembrolizumab was approved for bacillus Calmette-Guérin-unresponsive high-risk non-muscle invasive bladder cancer, opening the door for other immune checkpoint inhibitors to be integrated into treatment in earlier disease stages. Recent bacillus Calmette-Guérin shortages have highlighted the need for alternative treatment options for patients with non-muscle invasive bladder cancer. Currently, there are no FDA-approved checkpoint inhibitors for non-metastatic muscle-invasive bladder cancer. Furthermore, many patients are ineligible for standard cisplatin-based chemotherapy regimens. Numerous ongoing clinical trials are employing immune checkpoint inhibitors for muscle-invasive bladder cancer patients in the neoadjuvant, adjuvant, perioperative, and bladdersparing setting. Although up to 10% of urothelial carcinoma tumors arise in the upper urinary tract, few studies are designed for this population. We highlight the need for more trials designed for patients with upper tract disease. Overall, there are numerous clinical trials investigating the safety and efficacy of immune checkpoint inhibitors in all stages of disease as single-agents and combined with dual-immune checkpoint inhibition, chemotherapy, radiotherapy, and other pharmacologic agents. As the field continues to evolve rapidly, we aim to provide an overview of recent and ongoing immunotherapy clinical trials in urothelial carcinoma.

Keywords

Urothelial carcinoma (UC), Bladder cancer, Upper tract urothelial carcinoma (UTUC), Immunotherapy, Immune checkpoint inhibitors, PD-1, PD-L1

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