Uric Acid-Driven Biomarkers and Clinical Outcomes in Metastatic Pancreatic Cancer: A Multicenter Real-World Cohort Study

Background/Objectives: Metastatic pancreatic cancer is a highly lethal disease, and clinically useful biomarkers for outcome stratification are limited. Uric acid reflects systemic metabolic stress and inflammatory signaling, suggesting potential relevance as a tumor–host biomarker. However, the clinical significance of uric acid-based composite biomarkers in pancreatic cancer remains unclear. Methods: In this multicenter retrospective cohort study, 110 patients with metastatic pancreatic adenocarcinoma treated between 2015 and 2024 were analyzed. Sex-adjusted uric acid-based biomarkers were calculated using uric acid z-scores normalized by sex and integrated with markers of nutritional and immune status, including the uric acid z-score-to-albumin ratio (UAzAR) and uric acid z-score-to-lymphocyte ratio (UAzLR). Associations with overall survival (OS), progression-free survival (PFS), and chemotherapy response were evaluated using Kaplan–Meier analysis, Cox proportional hazards models, receiver operating characteristic (ROC) analyses, and multivariate logistic regression. Results: The median OS and PFS for the entire cohort were 12.6 months (95% CI 11.3–13.9) and 7.5 months (95% CI 6.6–8.4), respectively. Patients with high UAzAR had significantly shorter OS than those with low UAzAR (7.3 vs. 16.4 months; log-rank p < 0.001), and similar findings were observed for UAzLR (7.4 vs. 16.4 months; p < 0.001). In multivariate Cox models, elevated UAzAR independently predicted inferior OS (HR] 3.10, 95% CI 1.58–6.09; p = 0.001) and PFS (HR 2.35, 95% CI 1.22–4.52; p = 0.010), while elevated UAzLR was similarly associated with reduced OS (HR 3.28, 95% CI 1.68–6.39; p < 0.001) and PFS (HR 2.47, 95% CI 1.30–4.70; p = 0.006). High UAzAR and UAzLR were also independently associated with chemotherapy failure (adjusted odds ratio [OR] 5.52, 95% CI 2.16–14.06 and OR 6.42, 95% CI 2.49–16.55; both p < 0.001). In ROC analyses, UAzAR and UAzLR demonstrated moderate discrimination for 12-month OS (AUC 0.659 and 0.658) and stronger discrimination for 6-month PFS (AUC 0.705 and 0.692). Conclusions: Sex-adjusted uric acid-derived composite biomarkers independently predict survival and chemotherapy response in metastatic pancreatic cancer and may identify a high-risk metabolic phenotype relevant for clinical risk stratification.