Prognostic Value of the Lung Immune Prognostic Index in Advanced Non–Small Cell Lung Cancer Receiving Nivolumab: A Real-World Analysis Beyond PD-L1 Expression

Background: Non–small cell lung cancer (NSCLC) is one of the most commonly diagnosed malignancies and a leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors such as nivolumab have become a standard option in the second-line and later-line settings, identifying patients who derive meaningful benefit remains challenging. Established biomarkers, including PD-L1 expression, have shown limited predictive performance. The Lung Immune Prognostic Index (LIPI), a simple score reflecting systemic inflammation and tumor burden, has emerged as a potential prognostic tool. However, its real-world prognostic value in patients receiving nivolumab after first-line therapy remains insufficiently defined. Methods: This retrospective, single-center study included 109 patients with advanced NSCLC who received nivolumab following disease progression after first-line therapy. LIPI was calculated based on derived neutrophil-to-lymphocyte ratio (dNLR ≥3) and lactate dehydrogenase (LDH) levels above the upper limit of normal. Patients were stratified into three groups (LIPI 0-1-2). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan–Meier method and compared with the log-rank test. Multivariable Cox proportional hazards models were used to identify independent prognostic factors. Results: Patients were categorized as LIPI 0 (n=32), LIPI 1 (n=45), and LIPI 2 (n=32). A clear stepwise deterioration in outcomes was observed across increasing LIPI categories. Median PFS was not reached in the LIPI 0 group, and was 340 days and 109 days in the LIPI 1 and LIPI 2 groups, respectively (p < 0.001). Similarly, median OS was not reached in the LIPI 0 group, while it was 820 days and 201 days in the LIPI 1 and LIPI 2 groups, respectively (p < 0.001). In multivariable analysis, LIPI remained independently associated with both PFS and OS. In contrast, PD-L1 expression and other clinicopathological variables were not independently associated with survival outcomes, suggesting that the prognostic impact of LIPI is independent of PD-L1. Conclusions: LIPI appears to be a robust, readily available prognostic marker in patients with advanced NSCLC treated with nivolumab beyond the first-line setting. Its independent association with survival outcomes, irrespective of PD-L1 expression, suggests that it captures distinct biological processes related to systemic inflammation. Incorporation of LIPI into routine clinical practice may improve risk stratification and support more individualized treatment decisions. Notably, LIPI may provide complementary prognostic information beyond tumor-specific biomarkers such as PD-L1.