Pretreatment Lactate Dehydrogenase-to-Albumin Ratio and Clinical Outcomes in Extensive-Stage Small Cell Lung Cancer:...

Background: Reliable biomarkers that capture tumor-host interactions and predict treatment resistance in extensive-stage small cell lung cancer (SCLC) remain limited. We evaluated the prognostic and predictive value of the pretreatment lactate dehydrogenase-to-albumin ratio (LAR), an integrative biomarker reflecting metabolic activity, systemic inflammation, and host nutritional status. Methods: This multicenter, retrospective cohort study included patients with extensive-stage SCLC treated at five tertiary centers between 2016 and 2024. Pretreatment LAR was calculated using baseline serum lactate dehydrogenase and albumin levels and dichotomized using a Youden index-derived cut-off at the 12-month overall survival (OS) horizon. Time-dependent receiver operating characteristic (ROC) analyses using inverse probability weighting were performed to assess discriminative performance. Survival outcomes were evaluated using Kaplan-Meier estimates and Cox proportional hazards models. Associations with platinum resistance and lack of objective treatment benefit (defined as progressive disease as best response) were examined using logistic regression models. Results: A total of 223 patients were included. Elevated LAR was associated with inferior OS (median, 15.8 vs. 25.2 months; log-rank p < 0.001) and progression-free survival (7.9 vs. 11.5 months; p < 0.001). In multivariable analysis, LAR remained independently associated with OS (HR, 1.43; 95% CI, 1.04-1.95; p = 0.028). LAR demonstrated modest but consistently superior discriminative performance compared with other inflammatory indices for both 12-month OS (area under the curve [AUC], 0.692) and 6-month progression-free survival (PFS) (AUC, 0.646), with statistically significant differences in DeLong comparisons. Higher LAR was independently associated with increased odds of platinum resistance (adjusted odds ratio [aOR], 2.31; 95% CI, 1.41-3.81; p = 0.001) and lack of objective treatment benefit (adjusted OR, 2.04; 95% CI, 1.33-3.14; p = 0.001). Conclusions: Pretreatment LAR is a clinically accessible and biologically integrative biomarker associated with survival and treatment resistance in extensive-stage SCLC. By capturing tumor-host interactions, LAR may support risk stratification and identify patients at increased risk of early treatment failure. Prospective validation is warranted to define its role in biomarker-driven clinical decision-making.