ArticleTranslational lung cancer research2025
Survival benefits in non-small cell lung cancer during the immune checkpoint inhibitor era: integrating lymph node burden for prognostic precision.
Article in Translational lung cancer research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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1 citing paper in PubMed, 1 synthesis or guideline pooled it.
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9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Lung cancer remains a global health challenge, with non-small cell lung cancer (NSCLC) comprising the majority of cases. Since 2015, immunotherapy, specifically immune checkpoint inhibitors (ICIs), has significantly shifted treatment paradigms in advanced NSCLC, yet the prognostic role of lymph node metastatic burden remains underexplored. This study evaluates the survival benefit associated with the ICI era in advanced NSCLC and explores the prognostic value of lymph node burden metrics across disease stages. Methods: Using Surveillance, Epidemiology, and End Results data (SEER, 2010-2021), we identified advanced NSCLC patients and divided them into two cohorts based on the treatment era: pre-ICI era cohort (2010-2014) and ICI-introduction era cohort (2015-2021). Overall survival (OS) and cancer-specific survival (CSS) were analyzed in this advanced-stage population. Lymph node burden was assessed using the number of positive lymph nodes (NPLN), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS). Mediation analysis and SHapley Additive exPlanations (SHAP) modeling were used to evaluate their contribution to survival benefits. Additionally, we independently assessed the prognostic value of LNR and LODDS for OS and CSS, both in advanced-stage patients and a separate validation cohort of early-stage NSCLC with nodal metastasis, to evaluate their clinical utility beyond anatomical staging. Results: In patients with advanced NSCLC, the ICI-introduction era cohort demonstrated significantly improved OS and CSS compared to the pre-ICI era cohort, with adjusted hazard ratios (HRs) of 0.80 [95% confidence interval (CI): 0.75-0.85] and 0.76 (95% CI: 0.71-0.81), respectively. Mediation analysis indicated that LNR and LODDS partially explained these survival benefits. Besides, each 1% increase in LNR and each unit increase in LODDS were associated with an 87% (HR =1.87, 95% CI: 1.69-2.06) and 19% (HR =1.19, 95% CI: 1.16-1.22) increase in all-cause mortality risk, respectively. In early-stage NSCLC, both LNR and LODDS were strongly associated with mortality risk, and their integration with anatomical staging provided additional prognostic insight. Kaplan-Meier and Cox regression analyses confirmed enhanced survival stratification when combining rate-based lymph node metrics with anatomic staging. Conclusions: The approval and integration of immunotherapy has contributed, to some extent, to improved OS in advanced NSCLC at the population level, potentially mediated in part by reductions in metastatic lymph node burden. The rate-based metrics can also improve survival stratification in early-stage NSCLC, informing refinements to Tumor-Node-Metastasis (TNM) staging and personalized treatment strategies.
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