Rates of Nodal Upstaging following Systematic Endobronchial Ultrasound Lymph Node Staging in Non-Metastatic Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis

INTRODUCTION: Accurate hilar and mediastinal staging is critical for prognosis and treatment selection in non-metastatic non-small cell lung cancer (NSCLC). While current guidelines recommend systematic mediastinal lymph node staging by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for early-stage disease, its utility in wider populations is increasingly recognized. We aimed to determine the rate of nodal upstaging following systematic endoscopic mediastinal staging in non-metastatic NSCLC. METHODS: MEDLINE, Embase, and Cochrane databases were searched from inception to February 2025. We included prospective and retrospective studies of adults with curative-intent NSCLC undergoing systematic EBUS-TBNA staging that reported per-patient nodal upstaging. Two reviewers independently extracted data. A random-effects meta-analysis assessed the pooled proportion of PET-occult lymph node metastases. Upstaging rates were quantified across clinical N stages. Subgroup analyses and meta-regression assessed methodological variables (PROSPERO: CRD42024547873). RESULTS: Twenty-six studies comprising 5,161 participants were included. The pooled rate of PET-occult nodal metastases was 8.6% (95% CI: 6.7-11.0%), corresponding to a number needed to test of 12. Nodal upstaging rates varied by clinical stage: 7.2% for cN0, 10.6% for cN1, 5.0% for cN2, and 0.3% for cN3. Statistical heterogeneity was substantial (I2 = 82.0%); however, subgroup analyses and meta-regression did not identify significant sources of variance. CONCLUSION: This is the first published systematic review to evaluate the rate of PET-occult nodal disease in non-metastatic NSCLC using systematic staging EBUS-TBNA. Approximately 1 in 12 patients were identified to have PET-occult nodal metastases. These findings support the routine implementation of systematic endoscopic staging to guide curative-intent treatment decisions across non-metastatic disease stages.