[¹⁸F]F-FAPI PET/CT is superior to [¹⁸F]F-FDG PET/CT for lymph node staging in lung cancer: a pathologically validated study.

Abstract

Accurate lymph node staging in lung cancer remains challenging. This study evaluates the diagnostic efficacy of fibroblast activation protein inhibitor (FAPI) versus fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) using histopathology as the reference standard. Thirty-two lung cancer patients with FDG-positive lymph nodes underwent [¹⁸F]F-FAPI PET/CT. Pathological confirmation of 71 lymph nodes (23 metastatic, 48 benign) was obtained via surgery or endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Diagnostic efficacy was evaluated on both lymph node-based and patient-based, including maximum standardized uptake value (SUV_max), tumor-to-background ratio (TBR), sensitivity, specificity, accuracy, positive predictive value (PPV) and negative predictive value (NPV) . Metastatic lymph nodes showed significantly higher FAPI uptake vs. benign lymph nodes [SUV_max: (13.6 ± 9.6) vs. (2.7 ± 1.9)]; p < 0.001). Receiver operating characteristic (ROC) analysis showed a significantly larger area under the curve (AUC) for [¹⁸F]F-FAPI compared to [¹⁸F]F-FDG [AUC 0.98 (95% CI 0.95-1.0) vs. AUC 0.78 (0.65-0.89), (p < 0.001)]. In this cohort of patients with FDG-positive lymph nodes, [¹⁸F]F-FAPI presented greater lymph node detection sensitivity, specificity, accuracy, PPV and NPV than [¹⁸F]F-FDG (100% vs. 100%, 91.7% vs. 16.7%, 97.0% vs. 43.9%, 85.2% vs. 36.5% and 100% vs. 100% respectively). When the cut-off value of SUVmax is greater than 5.3, [¹⁸F]F-FAPI can correctly identify all 23 metastatic lymph nodes with much lower false positive rate than [¹⁸F]F-FDG (0% vs. 83.3%). [¹⁸F]F-FAPI shows higher lymph node staging accuracy than [¹⁸F]F-FDG [93.8% (30/32) vs. 43.8% (14/32)], led to downstaging in 15 patients. In 42.9% (9/21) of patients who underwent EBUS-TBNA, the procedure could have been safely avoided. [¹⁸F]F-FAPI PET/CT is a promising tool for lymph node staging of lung cancer, offering higher specificity and reduced false positives, with potential to optimize invasive staging procedures.