Time to refine N2 staging? cN2 and cN2 based on local regional involvement provide a more accurate prognosis in surgically treated IIIA non-small-cell lung cancer than N2 alone or the number of node stations involved

Abstract

The number of stations of N2 nodes involved has been considered to be one of the most important prognostic factors for lung cancer. However, most reports have dealt with the pathological nodal status rather than with the clinical nodal status. We investigated the relationship between the prognosis and the location of the primary tumour and nodes involved. A retrospective study was conducted in 1257 patients with primary lung cancer, which were resected between 1996 and 2009. Among them, 78 patients (6.2%) had cN2, c-stage IIIA, pN2 and non-small-cell lung cancer. We defined cN2α as only involvement of an upper mediastinal lymph node (UMLN) for a main tumour located in the upper lobe or as that of a lower mediastinal lymph node (LMLN) for a main tumour located in the lower lobe. cN2β was defined as involvement of an LMLN for a main tumour located in the upper lobe with or without metastatic UMLN or as that of a UMLN for a main tumour located in the lower lobe with or without metastatic LMLN. We analysed preoperative clinical factors, as well as overall and disease-free survival. The overall 5-year survival rate was 30.6%, and the disease-free 5-year survival rate was 22.6%. The disease-free 5-year survival rate for a tumour located in an upper lobe was significantly better than that for a tumour located in a lower lobe (27.9 vs 11.1%, P = 0.007). A significant difference in survival was seen between cN2α and cN2β (29.6 vs 0%, P < 0.001), but not between cN2 single and multiple (23.4 vs 19.5%, P = 0.123). A multivariate analysis with Cox's proportional hazards model revealed that cN2α independently predicted good disease-free survival. The sensitivity, specificity and positive predictive value for pN2 single based on clinical CT findings were 72.7, 48.2 and 35.6%, respectively. Clinical mediastinal lymph node status based on the location of the primary tumour and the node involved was an important preoperative prognostic factor. Thus, this factor should be considered when planning and evaluating clinical trials. Another important finding was that clinical single-station N2 is not always pathological single-station N2 disease.