Factors that Influence Non-Small Cell Lung Cancer Prognosis

The lymph node staging in non-small cell lung cancer (NSCLC) patients with stage IV M1a disease may carry a clinical significance that impacts prognosis, according to an analysis published in the Journal of Thoracic Oncology.

Back in 2007, a new category called M1a was added to stage IV classification in the 7^th edition of TNM Classification for Lung Cancer. M1a is defined as metastases within the chest, including contralateral pulmonary nodules, pleural dissemination, and pericardial dissemination.

Of the 3 components in the TNM Classification, the lymph nodal component (N) is an important determinant for establishing a cancer patients stage of disease, preferred treatment strategy, and prognosis. In M0 patients, lymph node metastases are an important determinate of staging, as well as a prognosis factor, while M1a patients are considered stage IV regardless of N status.

For the study, researchers used 39,731 patients with NSCLC M1a from the Surveillance, Epidemiology, and End Results (SEER) database from January 2005 to December 2012. Researchers compared lung cancer-specific survival (LCSS) among M1a patients classified by N stage.

Next, they applied the cox proportional hazards regression model to evaluate the prognostic factors. Additionally, statistical analysis was performed in all of the subgroups.

The results of the study 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 disease (N1 versus N2, p < 0.001). N1 was defined as metastasis in ipsilateral peribronchial, perihilar, and intrapulmonary lymph nodes.

When observing N2 and N3 disease, there was no difference found in LCSS (N2 versus N3, p=0.478). However, similar trends were seen when patients were subdivided into 2 temporal cohorts (2005-2008 and 2009-2012), and when M1a patients were subdivided into contralateral pulmonary nodules and pleural dissemination.

A difference in LCSS between N2 and N3 was seen in patients with malignant pleural nodules (p=0.003), according to the study. During the multivariable analysis, the lymph node metastasis became a significant prognostic factor for 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).

These same trends were found when pleural dissemination was divided into malignant pleural effusion or pericardial effusion and malignant pleural nodules.

“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,” said study authors. “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 significant among NSCLC patients with M1a disease, adding prognostic information.”