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

Urinary pH is a low-cost host-related marker, but its association with immune checkpoint inhibitor outcomes in advanced urothelial carcinoma is uncertain.

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.

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.

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.