Lung cancer is the most common and fatal type of cancer with approximately 50% of new cases diagnosed at stage IV. In 2007, the 7th edition of TNM Classification for Lung Cancer added a new category, M1a, to stage IV classification. The M1a disease is defined as metastases within the chest cavity including pleural dissemination, pericardial dissemination, and contralateral pulmonary nodules. Among the three components in the TNM Classification, the lymph nodal component (N), is an important determinant in establishing the stage of the patient, preferred treatment strategy, and the prognosis of disease. In M0 patients, lymph node metastases is an important prognostic factor and determinate of staging, whereas M1a patients are considered stage IV regardless of N status. The clinical effect of N status on M1a patients has not been extensively evaluated and warrants further exploration.
A group of investigators selected 39,731 NSCLC M1a patients from the Surveillance, Epidemiology, and End Results (SEER) database between January 2005 — December 2012. Lung cancer-specific survival (LCSS) was compared among M1a patients stratified by N stage. Cox proportional hazards regression model was applied to evaluate the prognostic factors. Statistical analysis was performed in all subgroups.
The results of the study published in the Journal of Thoracic Oncology, the official journal of the International Association for the Study of Lung Cancer (IASLC), showed that M1a patients with no regional lymph node metastasis (N0) had a better LCSS (N0 versus N1, p 0.001), followed by patients with N1 (metastasis in ipsilateral peribronchial, perihilar and intrapulmonary lymph nodes) disease (N1 versus N2, p 0.001). No difference in LCSS was observed between N2 and N3 disease (N2 versus N3, p = 0.478). Similar trends were observed when patients were subdivided into two temporal cohorts (2005-2008 and 2009-2012), as well as when M1a patients were subdivided into contralateral pulmonary nodules and pleural dissemination (malignant pleural effusion or pericardial effusion and pleural nodules). A difference in LCSS between N2 and N3 was observed in patients with malignant pleural nodules (p = 0.003).
In the multivariable analysis, lymph node metastasis emerged as a significant prognostic factor for both M1a patients with pleural dissemination or contralateral pulmonary nodule. Patients with pleural dissemination reported N1 versus N0: HR, 1.11 (95% CI, 1.06-1.17; p 0.001); N2 versus N0: HR 1.29 (95% CI, 1.25-1.33; p 0.001); N3 versus N0: HR, 1.35 (95%, 1.29-1.40; p 0.001) and in patients with contralateral pulmonary nodule, N1 versus N0: HR, 1.22 (95% CI, 1.01-1.36; p 0.001); N2 versus N0: HR, 1.52 (95% CI, 1.43-1.62; p 0.001); N3 versus N0: HR, 1.61 (95% CI, 1.49-1.73; p 0.001). The same trends were observed when pleural dissemination was divided into malignant pleural effusion or pericardial effusion and malignant pleural nodules.
The authors comment that, “Lymph node involvement is an important demarcation criterion for the staging of M0 patients while M1a patients are all staged as IV, regardless of any N status. Hence, the clinical value of N descriptors has been neglected and not well studied in M1a patients. However, our study found that the extent of lymph node metastasis also has the prognostic value for M1a patients. Specifically, M1a patients without lymph node involvement had the best survival, followed by those with N1 disease. These results provide preliminary evidence that lymph node stage may have clinical significance among NSCLC patients with M1a disease, adding prognostic information.”