Predictors of lymph node metastasis and possible selective lymph node dissection in clinical stage IA non-small cell lung cancer

Background: The pathologic stages of lymph nodes usually differ from preoperatively predicted in lung cancers and it is difficult to predict the metastasis of lymph nodes for the patients diagnosed as clinical stage IA non-small cell lung cancers (NSCLC). This study aimed to investigate the patterns of lymph node metastasis and the risk factors predicting lymph node metastasis in the patients with clinical stage IA NSCLCs. Methods: All patients diagnosed as clinical stage IA NSCLC from July 2013 to June 2017 in our center were retrospectively reviewed, and a total number of 1,543 patients who underwent anatomical lobectomy with systematic lymph node dissection were enrolled in this study. Multivariate logistic regression analysis was performed to identify the risk factors predicting lymph node metastasis, and Fisher's exact test was used to confirm the lymph node spread mode according to the locations of primary tumors. Results: Totally, lymph node metastases presented in 131 patients (8.5%) in this series. Sixty-three patients presented N1 diseases, 17 patients showed only skipped N2 diseases, and 51 patients had simultaneous N1 and N2 positive lymph nodes. No lymph node metastasis was found in the patients with pure ground grass opacity (GGO). When patients were arbitrarily divided into six groups by the longest tumor diameter of <= 0.5, 0.6-1, 1.1-1.5, 1.6-2.0, 2.1-2.5, 2.6-3 cm, the lymph node metastasis rates of each group were 0% (0/20), 1.5% (4/264), 4.7% (20/429), 8.6% (29/336), 13.1% (38/290), 19.6% (40/204), respectively. When the patients with pure GGO were excluded, the lymph node metastasis rates in the patients with partial or total solid tumors were 0% (0/10), 2.4% (4/164), 6.6% (20/303), 11.7% (29/249), 16.0% (38/238) and 23.1% (40/173). The cut off value showed by receiver operating characteristic (ROC) curve for tumor size was 1.95 cm, and the area under the curve (AUC) was measured as 0.681 (P<0.001, 95% CI: 0.630-0.726). Multivariate logistic regression analysis indicated that male patients [odds ratio (OR) =3.34, P=0.012], smoking history (OR =14.12, P<0.001), solid components (OR =3.34, P=0.0l), large tumor size (OR =1.9, P<0.001), poor differentiation (OR =2.25, P=0.013), lymphovascular invasion (OR =58.45, P<0.001), visceral pleural invasion (OR =48.37, P<0.001) were significantly associated with lymph node metastasis in clinical stage IA NSCLC. The rate of non-lobe specific lymph node metastasis was 15.8-40.0% when any of the lobe specific lymph nodes was positive, while it was only 0-2.2% when all lobe specific lymph nodes were negative. Conclusions: Tumor size, solid components, poor differentiation, lymphovascular invasion, visceral pleural invasion and smoking history were significant factors predicting lymph node metastasis of clinical stage IA NSCLC. Patients with negative lobe-specific lymph node have very low risk of metastasis to the non-lobe specific lymph nodes. Lobe-specific lymph node dissection may become an alternative lymph node dissection mode for clinical stage IA NSCLC, especially for tumors <= 2 cm.