Immune Checkpoint Inhibitors in the Management of Urothelial Carcinoma
Open Access
- 30 June 2021
- journal article
- Published by Scientific Archives LLC in Journal of Cancer Immunology
- Vol. 3 (2), 115-136
- https://doi.org/10.33696/cancerimmunol.3.047
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-fine 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 bladder-sparing 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
This publication has 68 references indexed in Scilit:
- Adjuvant Chemotherapy for Invasive Bladder Cancer: A 2013 Updated Systematic Review and Meta-Analysis of Randomized TrialsEuropean Urology, 2014
- Incidence and survival of patients with carcinoma of the ureter and renal pelvis in the USA, 1973–2005BJU International, 2010
- Environmental factors involved in carcinogenesis of urothelial cell carcinomas of the upper urinary tractBJU International, 2009
- Healthcare economics of bladder cancer: cost-enhancing and cost-reducing factorsCurrent Opinion in Urology, 2008
- PD-1 and Its Ligands in Tolerance and ImmunityAnnual Review of Immunology, 2008
- Management of BCG Failures in Superficial Bladder Cancer: A ReviewEuropean Urology, 2006
- The PD-1–PD-L pathway in immunological toleranceTrends in Immunology, 2006
- Adjuvant Chemotherapy in Invasive Bladder Cancer: A Systematic Review and Meta-Analysis of Individual Patient Data: Advanced Bladder Cancer (ABC) Meta-analysis CollaborationEuropean Urology, 2005
- Long-Term Survival Results of a Randomized Trial Comparing Gemcitabine Plus Cisplatin, With Methotrexate, Vinblastine, Doxorubicin, Plus Cisplatin in Patients With Bladder CancerJournal of Clinical Oncology, 2005
- Neoadjuvant Chemotherapy plus Cystectomy Compared with Cystectomy Alone for Locally Advanced Bladder CancerThe New England Journal of Medicine, 2003