Predictive Effect of Systemic Immune-Inflammation Index on Immunotherapy in Patients With Advanced Non-Small Cell Lung Cancer

Introduction The platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and systemic immune-inflammation index (SII) are emerging biomarkers for predicting outcomes in lung cancer. However, their prognostic value in advanced non-small cell lung cancer (NSCLC) patients receiving anti-PD-1/PD-L1 therapy remains uncertain. Methods In this retrospective study of 304 advanced NSCLC patients treated with ICIs, we evaluated PLR, NLR, and SII for associations with progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). Stratified analyses were performed based on patient age, lines of immunotherapy, PD-L1 expression, and baseline inflammatory marker levels. Results A total of 304 patients were included in the final analysis, with a median follow-up time of 18.6 months. The area under the curve (AUC) for 6-month PFS prediction was highest for SII (0.84), followed by NLR (0.746) and PLR (0.732). Using the optimal SII cutoff value of 776.415, patients were stratified into high and low SII groups. Multivariate analysis demonstrated that patients in the low SII group had significantly longer PFS (HR = 0.466, 95% CI: 0.319-0.681, P < 0.001) and OS (HR = 0.471, 95% CI: 0.317-0.699, P < 0.001) compared to the high SII group. Additionally, ORR was significantly higher in the low SII group (44.5% vs 29.5%, P = 0.007). In univariate analysis, patients with low PD-L1 expression (<50%) showed significantly shorter PFS (HR = 1.555, 95% CI: 1.059-2.284, P = 0.024) and OS (HR = 1.601, 95% CI: 1.075-2.384, P = 0.021) compared to those with high PD-L1 expression (≥50%). Conclusion For advanced NSCLC patients receiving anti-PD-1/PD-L1 therapy, lower SII values consistently may correlate with superior treatment response and survival outcomes. In clinical practice where conventional biomarkers like PD-L1 expression offer limited predictive value, SII emerges as a robust complementary indicator that may enhance immunotherapy strategy development.