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Hahn NM , Necchi A , Loriot Y , Powles T , Plimack ER , Sonpavde G , Roupret M , Kamat AM
Role of Checkpoint Inhibition in Localized Bladder Cancer
Eur Urol Oncol. 2018 Aug;1(3) :190-198
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CONTEXT: Checkpoint inhibitors (CPIs) are established as a standard therapy option for metastatic bladder cancer; however, their role in earlier-stage disease remains undefined. OBJECTIVE: 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. EVIDENCE ACQUISITION: 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. EVIDENCE SYNTHESIS: 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. CONCLUSIONS: 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. PATIENT SUMMARY: 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.
2588-9311 Hahn, Noah M Necchi, Andrea Loriot, Yohann Powles, Thomas Plimack, Elizabeth R Sonpavde, Guru Roupret, Morgan Kamat, Ashish M Journal Article Review Netherlands Eur Urol Oncol. 2018 Aug;1(3):190-198. doi: 10.1016/j.euo.2018.05.002. Epub 2018 May 30.