Urinary pH and Checkpoint Inhibitor Outcomes in Advanced Urothelial Carcinoma: An Exploratory Brief Report.

INTRODUCTION: Urinary pH is a low-cost host-related marker, but its association with immune checkpoint inhibitor outcomes in advanced urothelial carcinoma is uncertain. METHODS: We retrospectively reviewed 45 consecutive patients with advanced urothelial carcinoma who received pembrolizumab or avelumab and had urinary pH measured at treatment initiation. Baseline urinary pH was categorized as ≥6.5 or <6.5. Outcomes were objective response rate, progression-free survival, and overall survival. Cox models were adjusted for Bellmunt risk score. Early urinary pH dynamics were examined when available. RESULTS: Baseline urinary pH was ≥6.5 in 20 patients and <6.5 in 25. Objective response rate was 40.0% versus 16.0%, respectively. Baseline urinary pH ≥6.5 was associated with longer progression-free survival after Bellmunt adjustment (hazard ratio, 0.39; 95% confidence interval, 0.17-0.86), whereas the association with overall survival was weaker. Among 32 patients with early urinary pH data, objective response rate was 41.7% in the High-High group, 28.6% in the Low-High group, and 0% in the Low-Low group. In a pembrolizumab-only sensitivity cohort, the direction of association with real-world progression-free survival was preserved but attenuated. CONCLUSION: Urinary pH showed an exploratory association with checkpoint inhibitor outcomes. Because urinary pH is influenced by renal function, infection, medication, hydration, and diet, it should be interpreted as a hypothesis-generating host-related signal rather than a direct surrogate of tumor acidity.