Occult mediastinal lymph node metastasis in FDG‐PET/CT node‐negative lung adenocarcinoma patients: Risk factors and histopathological study

BACKGROUND: The aim of this study was to investigate predictive factors of occult mediastinal lymph node metastasis (MLNM) in preoperative (18)F‐fluorodeoxy‐glucose PET/CT node‐negative lung adenocarcinoma patients. METHODS: We reviewed the clinical data and PET/CT parameters of 360 consecutive pulmonary adenocarcinoma patients who were scheduled to undergo anatomical pulmonary resection and systemic mediastinal node dissection. The nodal metastasis was pathologically defined and all resected tumors were classified according to the 2011 IASLC/ATS/ERS classification. Univariate and multivariate analysis were conducted to evaluate the associations between clinicopathological variables and MLNM. RESULTS: Of all 360 patients, 54 (15.0%) had pathological N2 diseases. The serum CEA level, nodule type, hilar nodal SUVmax, tumor SUVmax, size, location and histologic subtype were associated with MLNM significantly on univariate analysis. On multivariate analysis, CEA ≥ 5.0 ng/mL (P < 0.001), solid nodule (P = 0.012), tumor SUVmax ≥ 3.7 (P < 0.027), hilar nodal SUVmax ≥ 2.0 (P < 0.001) and centrally located tumor (P = 0.035) were independent risk factors for MLNM. The area under the ROC curve (AUC) for tumor SUVmax and hilar nodal SUVmax in predicting MLNM was 0.764 and 0.730, respectively, and the combined use of five factors yielded a higher AUC of 0.885. CONCLUSION: Increased primary tumor and hilar lymph node SUVmax, solid nodule, centrally located tumor and increased CEA level predicted the increased risk of mediastinal lymph node metastasis. Combined use of these factors improved the diagnostic capacity for predicting N2 disease preoperatively. Invasive mediastinal staging should be considered for patients with these risk factors, even those with a negative mediastinum on PET/CT.