Objective:

To explore the efficacy and safety of gemcitabine combined with tislelizumab as initial treatment for patients with locally advanced or metastatic urothelial carcinoma who are intolerant to platinum-based drugs.

Key Findings:

• 30 patients were enrolled by the data cutoff date (September 1, 2025).
• Median progression-free survival (mPFS) was 13.9 months (95% CI: 11.4–16.3).
• Median overall survival (mOS) was 23.3 months (IQR: 14.4–33.1; 95% CI: 18.2–28.3).
• Confirmed ORR was 46.7% (14/30; 95% CI: 28.3–65.7) and DCR was 76.7%.
• Most frequent treatment-related adverse events (TRAEs) included leukopenia (43.3%) and neutropenia (40.0%).
• Response rates differed by tumor-associated TLS status, with 66.7% in TLS positive and 35.3% in negative, but not statistically significant (P = 0.218).

Interpretation:

The combination of tislelizumab and gemcitabine showed manageable tolerability and promising preliminary efficacy as a first-line treatment for patients with locally advanced or metastatic urothelial carcinoma who cannot receive cisplatin.

Limitations:

• Single-center study may limit generalizability and applicability to broader populations.
• Small sample size may affect the robustness of findings and statistical power.
• Lack of statistical significance in TLS analysis suggests further investigation is needed.

Conclusion:

The findings warrant further investigation into the combination of tislelizumab and gemcitabine for this patient population, emphasizing the need for larger studies to validate these results.