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• W2806413184 abstract "Checkpoint inhibitors (CPIs) are established as a standard therapy option for metastatic bladder cancer; however, their role in earlier-stage disease remains undefined. To summarize the preclinical and clinical evidence forming the rationale for multiple ongoing investigations of CPIs in patients with localized bladder cancer defined by non–muscle-invasive or muscle-invasive stages. A systematic review of the literature in the MEDLINE database was performed. The central search strategy used the terms bladder cancer, urothelial carcinoma, transitional cell, localized, muscle-invasive, non–muscle-invasive, superficial, PD-1, PD-L1, CTLA-4, and checkpoint inhibitor, both alone and in combination. The search was limited to publications between January 2000 and December 2017. Publicly available relevant abstracts from recent meetings were also included. Preclinical immunocompetent murine, rodent, and canine models have each demonstrated proof-of-concept support for CPI therapy approaches in localized urothelial carcinoma (UC). Retrospective analysis of localized UC tumor samples confirms the presence of PD-1, PD-L1, or CTLA-4 in a proportion of patients. Prospective pilot trials of CPI therapy in localized UC demonstrated enhanced adaptive immune response measures. Improved whole-transcriptome platforms may further refine patient selection for CPI therapy. Multiple clinical trials of CPI therapy in localized UC are under way with significant practice-changing potential. Evidence from preclinical models and retrospective data for patients with localized UC and metastatic UC sufficiently justifies the investigation of CPI approaches in the context of prospective clinical trials. Checkpoint inhibitor (CPI) therapy has provided durable tumor control in a small portion of patients with metastatic urothelial carcinoma (UC). Investigating the potential for similar sustained tumor control in localized UC is logical. Ongoing prospective clinical trials will define whether or not CPI therapy should be extended to patients with curable localized UC in whom standards for successful clinical outcomes are higher and acceptance rates of severe treatment-related toxicity are lower." @default.
• W2806413184 created "2018-06-13" @default.
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• W2806413184 date "2018-08-01" @default.
• W2806413184 modified "2023-09-25" @default.
• W2806413184 title "Role of Checkpoint Inhibition in Localized Bladder Cancer" @default.
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• W2806413184 doi "https://doi.org/10.1016/j.euo.2018.05.002" @default.
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