Abstract
Urothelial bladder cancer is one of the most lethal cancers worldwide with barely 5% five-year survival in patients with metastatic disease. Intravesical immunotherapy with Bacillus Calmette-Guérin and platinum-based chemotherapy are currently the standard of care for non-muscle invasive and advanced or metastatic urothelial cancer (mUC), respectively. Recently, a subset of patients with locally advanced or mUC has shown to be responsive to immune checkpoint inhibitors (ICIs), e.g., the anti-cytotoxic T-lymphocyte-associated protein 4 and programmed cell death -1/programmed death-ligand1 (PD-1/PD-L1) antibodies. Due to the relevant clinical benefit of immunotherapy for mUC, in 2016, the United States Food and Drug Administration (FDA) approved five immunotherapeutic agents as second-line or first-line treatments for patients with advanced bladder cancer who did not profit from or were ineligible for standard therapy. In this review, we discuss the role of immunotherapy in bladder cancer and recent clinical applications of PD-1/PD-L1 blockade in mUC. Furthermore, we evaluate a variable response rate to ICIs treatment and outline potential biomarkers predictive of immunotherapy response.
Highlights
Bladder cancer is the tenth most commonly diagnosed tumor worldwide with high morbidity and mortality of up to 165,000 deaths per year [1]
We evaluate a variable response rate to immune checkpoint inhibitors (ICIs) treatment and outline potential biomarkers predictive of immunotherapy response
We focus on the current status of immunotherapy in bladder cancer, highlighting advances in the identification of genomic and clinical biomarkers for predicting an ICI response
Summary
Bladder cancer is the tenth most commonly diagnosed tumor worldwide with high morbidity and mortality of up to 165,000 deaths per year [1]. Contrariwise, muscle-invasive and metastatic bladder carcinomas entail multimodal treatments including surgery and chemotherapy [5]. Immunotherapy has taken on a prominent role in oncology as a first-line monotherapy in numerous tumor types, including metastatic urothelial cancer (mUC), or, more frequently, in addition to conventional cancer treatments (i.e., surgery, chemotherapy, and radiotherapy) [6]. Intravesical therapy with Bacillus Calmette-Guérin (BCG) or chemotherapy are the mainstay of treatment following transurethral bladder tumor resection (TURBT) in non-muscle invasive carcinomas [9,10,11]. The mechanism behind the dissimilar reactions to ICIs among mUC patients has not been thoroughly elucidated, and variation in the response rate to these drugs for different tumor types have encouraged the search for biomarkers. We focus on the current status of immunotherapy in bladder cancer, highlighting advances in the identification of genomic and clinical biomarkers for predicting an ICI response
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