Diagnostic Accuracy of Preoperative PET-CT for Mediastinal Lymph Node Staging in NSCLC

ABSTRACT Background: Accurate mediastinal lymph node staging is essential in NSCLC treatment. While FDG-PET/CT is widely used for non-invasive staging, its diagnostic reliability, particularly for nodal assessment, remains debated. Methods: A retrospective multicenter analysis included 278 patients with histologically confirmed NSCLC who underwent FDG-PET/CT followed by surgery with systematic lymphadenectomy between 2015 and 2021. PET/CT-based nodal staging was compared with histopathology. Diagnostic performance was evaluated using sensitivity, specificity, positive and negative predictive values and Cohen’s κ. Logistic regression was performed to identify predictors of correct N-staging. Patients receiving neoadjuvant therapy were excluded from subgroup analyses (n = 252). Results: Histopathology revealed nodal metastases in 112 patients (40.3%). PET/CT detected nodal involvement with sensitivity of 66.8% and specificity of 85.2%. PPV was 50.7% and NPV 85.5%, with an overall concordance of 43.3%. Sensitivity for N1 disease was 38.2%, while N2 and N3 metastases were detected with sensitivities of 55.3% and 100.0%. The false-negative rate was 25.2%, with intrapulmonary nodes (station 11) most frequently missed. False-positive findings occurred in 20.1%, predominantly in hilar nodes. Multivariable analysis identified lymph node involvement and tumor stage as independent predictors of staging accuracy, whereas extracapsular extension showed a non-significant trend. Conclusion: FDG-PET/CT demonstrates high specificity and NPV but limited sensitivity for mediastinal nodal staging in NSCLC under real-world conditions. These findings are primarily driven by disease characteristics rather than methodological factors. A multimodal approach remains essential, with histopathological confirmation of PET-positive findings and selective invasive staging in PET-negative patients to ensure accurate treatment allocation.