Urologic oncology
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The success of immune checkpoint inhibitors in advanced urothelial carcinoma provides patients with the prospect for durable objective responses. However, the majority of patients do not respond to immune checkpoint blockade. ⋯ Going forward, development of reliable predictive biomarkers is imperative. Likewise, innovative treatment combination approaches to convert non-responders to responders are essential to continue making progress in the field.
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Checkpoint inhibitors have rapidly become a standard treatment option for metastatic urothelial carcinoma. A wave of enthusiasm for these drugs has pushed them also into the setting of localized bladder cancer, including both non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive disease bladder cancer (MIBC). Here, we aimed to review the emerging role of checkpoint inhibition in localized bladder cancer. ⋯ Ongoing trials would determine in the next several years whether checkpoint inhibitors can have a similar effect in localized disease as they have had in metastatic bladder cancer. They would also determine if patients with earlier disease would tolerate the toxicity of systemic therapy. The future holds promise for predictive biomarkers to guide individualized use of these agents and for effective combination therapies to overcome resistances.
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Urothelial bladder cancer is one of the first cancers recognized to be immunogenic since 40 years ago when the use of bacillus Calmette-Guerin was shown to prevent recurrence. Since that time, our knowledge of immune biology of cancer has expanded tremendously, and patients with bladder cancer finally have new active immunotherapeutic drugs on the horizon. Anti-programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PD-L1) therapy has shown impressively durable responses in urothelial bladder cancer (UBC), but the reported response rates warrant improvement. ⋯ As new immunotherapies are developed, predictive biomarkers would also be important to select patients most likely to respond and to better understand tumor biology. Several potential biomarkers are reviewed including PD-L1 expression, identification of T-cell-inflamed/non-T-cell-inflamed tumors based on immune gene expression, intrinsic molecular subtyping based on luminal/basal or the cancer genome atlas (TCGA) groups, T-cell receptor sequencing, and somatic mutational density. Even within the past few years, our current knowledge of immune biology has exploded, and we are highly optimistic about the future of UBC therapy that will be available to patients.
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Systemic therapy for metastatic urothelial carcinoma has seen minimal progress and no new approved therapies in the past 20 years. However, with the approval of the checkpoint inhibitor atezolizumab in May 2016, immunotherapy inserted itself into the standard clinical dogma. ⋯ Current and ongoing trials are investigating ways to increase response rates with rational combinations as well as to uncover predictive biomarkers to identify patients most likely to benefit. In this review, we present updated data regarding immunotherapeutic agents in clinical trials as well as ongoing studies investigating novel designs, intriguing combinations, and alternative immunotherapy strategies.