Lactate dehydrogenase-to-lymphocyte ratio predicts overall and progression-free survival among patients with advanced small-cell lung cancer receiving first-line chemoimmunotherapy

Platinum plus etoposide combined with programmed death-ligand 1 (PD-L1) inhibitors is the standard first-line therapy for patients with advanced small-cell lung cancer (SCLC). However, reliable prognostic biomarkers are yet to be identified. The lactate dehydrogenase-to-lymphocyte ratio (LLR) is a potential indicator of tumor metabolism and host immune response; a high LLR is correlated with a poor prognosis in other carcinomas. The LLR may be a more comprehensive indicator of prognosis than the neutrophil-lymphocyte ratio (NLR) or platelet-lymphocyte ratio (PLR), which mainly reflect host immune status. This study evaluates the prognostic value of the LLR in patients with SCLC receiving first-line chemoimmunotherapy. This retrospective, two-center study was conducted at 2 university hospitals in Japan and analyzed 64 patients with extensive-stage SCLC or post-chemoradiotherapy recurrence of limited-stage SCLC who received platinum-etoposide plus a PD-L1 inhibitor as first-line therapy between August 2019 and December 2023. The LLR, NLR, and PLR were calculated from blood tests immediately before the start of first-line therapy, and cutoff values were set using the X-tile software. The prognostic significance of these markers was assessed using Kaplan-Meier survival analysis and the Cox proportional hazards model. Of the 64 patients included, 10 (16%) had high LLR (>471.5). The median duration of observation was 10.5 months (interquartile range: 6.0-19.0 months); by the time of data cutoff, 56 patients (87.5%) had experienced progressive disease and 36 (56.3%) had died. The high LLR group had significantly shorter overall survival (OS) and progression-free survival (PFS). Multivariate analysis was performed using only those factors (LLR/ECOG PS/bone metastasis regarding OS and LLR/bone metastasis regarding PFS) identified as significant in univariate analyses. A high LLR was an independent predictor of worse OS and PFS. While the NLR was an independent prognostic factor for OS, neither NLR nor PLR was a significant predictor of PFS. The LLR is a novel potential prognostic biomarker that integrates tumor metabolism and host immunity in patients with SCLC receiving first-line chemoimmunotherapy. Because it can be readily calculated from routine blood tests, it may serve as a cost-effective tool for risk stratification. However, further prospective validation in larger cohorts is warranted.