Perioperative Immune Checkpoint Blockade for Muscle-Invasive and Metastatic Bladder Cancer

Area of Science:

• Oncology
• Immunology
• Cancer Research

Background:

• Checkpoint inhibitors are promising for bladder cancer but optimal timing (neoadjuvant vs. adjuvant) is unclear.
• Combining immunotherapy with chemotherapy is being explored for muscle-invasive and metastatic bladder cancer.

Purpose of the Study:

• To evaluate the efficacy and safety of neoadjuvant anti-PD-1 and anti-CTLA-4 with cisplatin-gemcitabine chemotherapy for muscle-invasive bladder cancer.
• To compare neoadjuvant versus adjuvant anti-PD-L1 efficacy in a murine model of metastatic bladder cancer.

Main Methods:

• Phase II trial of neoadjuvant immunotherapy plus chemotherapy in muscle-invasive bladder cancer patients.
• Murine model of spontaneous metastatic bladder cancer to assess neoadjuvant vs. adjuvant anti-PD-L1 therapy.

Main Results:

• The clinical trial was stopped early; 50% complete pathologic response in 4 patients with manageable adverse events.
• Treatment response correlated with increased urinary CD8+ and IFNγ+ CD4+ T cells.
• In murine models, both neoadjuvant and adjuvant anti-PD-L1 improved survival compared to immunotherapy alone, with no significant difference between timing strategies.

Conclusions:

• Neoadjuvant chemotherapy and immunotherapy combination appears safe for muscle-invasive bladder cancer.
• Perioperative immunotherapy shows potential for locally advanced and metastatic bladder cancer.
• Further randomized trials are needed to confirm immunotherapy efficacy in the neoadjuvant setting.