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Updated: Jan 24, 2026
Culture of Bladder Cancer Organoids as Precision Medicine Tools
Published on: December 28, 2021
Role of Checkpoint Inhibition in Localized Bladder Cancer
Noah M Hahn1, Andrea Necchi2, Yohann Loriot3
1The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA; Johns Hopkins Greenberg Bladder Cancer Institute, Baltimore, MD, USA.
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.
Insights
Checkpoint inhibitors (CPIs) show promise for localized bladder cancer, with preclinical and early clinical data supporting further investigation. Ongoing trials will determine if CPIs can offer durable control in earlier stages of urothelial carcinoma.
Area of Science:
- Oncology
- Immunotherapy
- Urothelial Carcinoma Research
Background:
- Checkpoint inhibitors (CPIs) are standard for metastatic bladder cancer, but their use in earlier stages is not yet defined.
- Localized bladder cancer includes non-muscle-invasive and muscle-invasive stages.
Purpose of the Study:
- To review preclinical and clinical evidence supporting CPI investigation in localized bladder cancer.
- To inform ongoing clinical trials of CPIs in non-muscle-invasive and muscle-invasive urothelial carcinoma.
Main Methods:
- Systematic literature review of MEDLINE database (2000-2017) and recent meeting abstracts.
- Search terms included bladder cancer, urothelial carcinoma, PD-1, PD-L1, CTLA-4, and checkpoint inhibitors.
- Inclusion of preclinical models and retrospective/prospective clinical data.
Main Results:
- Preclinical models demonstrate proof-of-concept for CPI therapy in localized urothelial carcinoma (UC).
- Retrospective analyses confirm PD-1, PD-L1, or CTLA-4 expression in localized UC.
- Pilot trials show enhanced immune responses; multiple trials are ongoing.
Conclusions:
- Preclinical and retrospective data justify prospective CPI trials in localized UC.
- Ongoing trials will clarify CPI efficacy and safety in curable bladder cancer stages.
- Refined patient selection may be possible with advanced genomic platforms.
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