Risk Factors for Predicting the Occult Hilar-Mediastinal lymph node Metastasis in Non-Small Cell Lung Cancer Patients with negative or symmetric uptake pattern on preoperative F-18 Fluorodeoxyglucose PET/CT

Background: Accurate nodal staging is crucial to the management and prognosis of non-small cell lung cancer (NSCLC) patients. N staging of NSCLC Patients with negative or symmetric uptake pattern in hilar and mediastinal lymph nodes (HMLNs) on preoperative 2- deoxy-2-[ ¹⁸ F] fluoro-D-glucose ( ¹⁸ F-FDG) PET/CT is difficult. This study aimed to explore risk factors for occult lymph node metastasis (OLNM) in NSCLC patients with negative or symmetric uptake patterns in HMLNs on preoperative ¹⁸ F-FDG PET/CT. Methods: We retrospectively analyzed patients with NSCLC who underwent pulmonary resection and regional lymph node dissection within 1 month after ¹⁸ F-FDG PET/CT. Patients with negative or symmetric uptake patterns in bilateral HMLNs and without distant metastasis on preoperative ¹⁸ F-FDG PET/CT were included. Postoperative pathology served as the gold standard for identifying OLNMs. Clinical, pathological characters, and image parameters were compared between patients with and without OLNMs. Results: A total of 91 patients (60 males; mean age 67.2± 9.0 years) were included. The median primary tumor size was 2.2cm. Post-surgery pathology identified OLNM in 12 patients (13.2%, including four in N2 stage and 8 in N1 stage). Among those, 5 (5/59) patients showed a symmetric uptake pattern, 7 (7/32) patients showed a negative uptake pattern in HMLNs. Univariate analysis revealed a significant difference in tumor size (4.0 cm vs. 2.1 cm, P=0.001), MTV (9.1 vs. 2.9, P=0.001), and TLG (81.1 vs. 15.0, P=0.001) between patients with and without OLNMs. Multivariate analysis identified primary tumor size as an independent risk factor for OLNM (OR=2.439, 95% CI: 1.311 to 4.536, P=0.005). The area under the ROC curve (AUC) of primary tumor size for OLNM prediction was 0.804 (P<0.001, 95% CI: 0.684 to 0.925). Conclusions: For NSCLC patients with negative or symmetric uptake pattern in HMLNs on preoperative ¹⁸ F-FDG PET/CT, primary tumor size is an independent predictor for OLNM.