PET/CT nodal pitfalls: The reality of false positivity and negativity in non- small cell lung cancer

Aim: To evaluate the diagnostic accuracy of preoperative 18F-FDG PET/CT for mediastinal and hilar lymph node staging in non-small cell lung cancer (NSCLC), using postoperative histopathology as the reference standard.

Materials and Methods: This retrospective single-center study included 37 NSCLC patients who underwent anatomical lung resection and systematic lymph node dissection between 2015 and 2020. PET/CT findings were compared with histopathology to calculate sensitivity, specificity, positive and negative predictive values, and accuracy. True-positive (TP) and false-positive (FP) cases were compared using Mann–Whitney U and Fisher exact tests. Firth penalized logistic regression assessed predictors of TP nodal metastasis.

Results: Of 37 patients, 89.2% were male, and mean age was 60.9 ± 7.7 years. Mean tumor diameter was 4.11 ± 2.02 cm, and mean SUVmax was 16.8 ± 7.5. PET/CT indicated nodal involvement in 33 patients (89.2%), while histopathology confirmed metastasis in 19 (51.4%). Sensitivity was 89.5%, specificity 11.1%, positive predictive value 51.5%, negative predictive value 50.0%, and accuracy 51.4%. Among PET-positive patients, TP cases had higher primary tumor SUVmax and larger tumors, with more frequent extracapsular extension (ECE) and pathological stage III disease. Firth regression identified tumor diameter (OR 1.74), ECE (OR 2.96), and stage III (OR 3.21) as independent predictors of TP status. FP findings clustered in stations 4 and 10, whereas false-negative findings occurred most often in stations 7 and 11.

Conclusion: PET/CT alone was insufficient for definitive nodal staging because of substantial false positivity and clinically relevant false negativity. Histopathological confirmation of PET-positive nodes, when indicated, may prevent mis-staging and inappropriate treatment selection while preserving curative surgical opportunities.