Elsevier

Clinical Lung Cancer

Volume 16, Issue 6, November 2015, Pages e203-e212
Clinical Lung Cancer

Original Study
Prognostic Significance of the Number of Metastatic pN2 Lymph Nodes in Stage IIIA-N2 Non–Small-Cell Lung Cancer After Curative Resection

https://doi.org/10.1016/j.cllc.2015.04.004Get rights and content

Abstract

Introduction

There have been controversies regarding the prognostic relevance of the number of positive N2 nodes in pathologic stage IIIA-N2 non–small-cell lung cancer (NSCLC). We examine prognosis of patients with pathologic stage IIIA-N2 with classifying the number of positive N2 nodes into subgroups.

Methods

From January 1997 to December 2004, 250 patients were diagnosed with pathologic stage IIIA-N2 disease. All patients underwent mediastinal lymph node dissection. After excluding 44 patients with preoperative chemotherapy, incomplete resection, and postsurgical mortality, 206 patients were included in the analysis. Patients were classified according to the number of positive N2 lymph nodes (N2a: 1 [n = 83], N2b: 2-4 [n = 82], N2c: ≥ 5 [n = 41]), and its correlation with survival outcomes were investigated.

Results

With a median follow-up of 96.3 months, 5-year disease-free survival (DFS) was 27.2% (95% confidence interval [CI], 21.6-33.7), and 5-year overall survival (OS) was 37.7% (95% CI, 31.5-44.7) in all patients. The number of metastatic N2 lymph nodes was associated with DFS (P < .001) and OS (P = .01). In the N2a, N2b, and N2c groups, 5-year DFS rates were 38%, 24%, and 5%, respectively, and 5-year OS rates were 47%, 35%, and 24%, respectively. In a multivariate analysis, the number of metastatic N2 lymph nodes was an independent prognostic factor for DFS and OS.

Conclusion

Stratification of patients according to the number of metastatic N2 lymph nodes may improve the accuracy of prognostic prediction among patients with curatively resected stage IIIA-N2 NSCLC.

Introduction

Stage IIIA-N2 non–small-cell lung cancer (NSCLC) is a potentially operable, locally advanced disease. Because pathologically confirmed N2 (pN2) disease is classified according to the presence of mediastinal nodal metastasis regardless of its extent, it includes a broad spectrum of presentations, from occult disease to multiple mediastinal nodal metastases. As a consequence, stage IIIA-N2 NSCLC has been linked to a variable prognosis in previous studies, with 5-year survival rates ranging from 6% to 35%.1, 2

Although cisplatin-based adjuvant chemotherapy has led to significant improvements in survival in patients with resected NSCLC, particularly stage II and IIIA disease,3, 4, 5 the optimal management of stage IIIA-pN2 disease remains largely unknown, mainly as a result of the prognostic heterogeneity of this patient subgroup. With the hypothesis that the extent of pN2 metastasis may have prognostic relevance in patients with curatively resected stage IIIA-N2 NSCLC, several subclassifications of patients with pN2 disease have been proposed to improve staging—for example, based on skip pN2 metastasis6, 7 or pN2 nodal station numbers.8, 9, 10, 11, 12 Although the prognostic implication of the number of metastatic lymph nodes in resected NSCLC has been explored in previous studies, its relevance in pathologic stage IIIA-N2 disease has not been clearly demonstrated.13, 14, 15 To investigate this, we retrospectively assessed whether the risk of disease relapse and survival after complete surgical resection could be stratified according to the number of metastatic pN2 lymph nodes in patients with IIIA-N2 NSCLC.

Section snippets

Patients

Between January 1997 and December 2004, 250 patients with pathologically confirmed stage IIIA-N2 NSCLC were selected for inclusion from a prospectively collected patient database of the Asan Medical Center, Seoul, Korea. According to the preoperative staging assessment, all patients were determined to have curatively resectable disease by the attending surgeons. Of these, 44 patients were excluded as a result of preoperative induction chemotherapy (n = 28), incomplete resection (n = 11), and

Patient Characteristics

The patients' baseline characteristics are summarized in Table 1. The median age was 59 years, and 145 patients (71%) were male. Significant weight loss was reported in 34 patients (17%) at the time of diagnosis. In 73 patients (35%), PET scan was performed for initial clinical staging. N2 nodal metastasis was predicted in 68 patients (33%) at the preoperative staging assessment, and pneumonectomy was performed in 43 patients (21%). According to the number of pN2 metastases, 83 patients (40%)

Discussion

The prognosis of patients with resected stage IIIA-N2 NSCLC is heterogeneous, and better prognostic prediction is required for tailored therapy in this group of patients. However, many researchers have indicated that in patients with NSCLC, the current tumor, node, metastasis staging classification system does not accurately reflect the extent of mediastinal nodal metastasis that may be closely associated with survival outcomes. To circumvent this problem, a variety of pN2 subclassifications

Conclusion

The number of metastatic pN2 lymph nodes is an independent predictor of DFS and OS in patients with stage IIIA-N2 NSCLC after curative surgery. This may have an application in clinical practice and trials, where risk stratification is important. Further studies to validate this pN2 subclassification in other populations are warranted.

Disclosure

The authors have stated that they have no conflicts of interest.

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    • Cited by (0)

    This study was presented in part as a poster at the 2010 ASCO Annual Meeting, June 4-9, 2010, Chicago, IL, USA.

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