The prognostic impact of lymph node metastasis in patients with non-small cell lung cancer and distant organ metastasis
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This study aimed to identify the prognostic value of lymph node metastasis in patients with non-small cell lung cancer (NSCLC) and distant organ metastasis. A total of 42,613 NSCLC patients with distant metastasis from the surveillance, epidemiology, and end results database between 2010 and 2013 were included for analysis. The proportion of N0 stage in M1a patients was significantly higher than that in M1b patients, 34.0% and 22.7% respectively (P < 0.001). Compared with N0 patients, patients had higher odds of experiencing multiorgan metastases (MOM) if they had higher N stage at diagnoses (P < 0.001). The Kaplan–Meier curves suggested both M1a and M1b groups patients at stage N0 had better survival than those at higher N stage (P < 0.001). Further analysis indicated that better survival was observed in N0 stage compared with N2 or N3 stage if patients had bone metastasis, brain metastasis, or MOM (P < 0.001, P < 0.001, and P = 0.002, respectively), but there was no significant difference in survival among each N stage patients with liver metastasis only. Cox regression analysis showed that compared with N0 patients, higher hazard for disease-specific mortality was observed for patients with higher N stage. Among NSCLC patients with distant organ metastasis, lymph node metastasis was associated with higher odds of experiencing MOM and a worse prognosis in terms of longer survival except patients with liver metastasis. Better understandings of the role of lymphatic metastasis in M1 NSCLC could help clinicians with better management of the disease.
KeywordsNon-small cell lung cancer Lymph node metastasis Distant metastasis Prognosis SEER
American Joint Committee on Cancer
International Association for the Study of Lung Cancer
Non-small cell lung cancer
Surveillance, epidemiology and end results
Squamous cell carcinoma
Tumor, node, and metastasis
We would like to thank all the staff of National Cancer Institute for their effort to the SEER program.
Conception and design: J.Y., G.J., and P.Z.; Acquisition, statistical analysis or interpretation of the data: All authors; Drafting of the manuscript: J.Y., A.P., and B.W.; All authors reviewed and approved the final version of the manuscript.
This work was supported by National Natural Science Foundation of China No. 81600052 (J. Y.) and the Fundamental Research Funds for the Central Universities No. 22120180022 (J. Y.).
Compliance with ethical standards
Conflicts of interest
The authors disclose no potential conflicts of interest related to this study.
Our study was approved by the ethical committee board of Shanghai Pulmonary Hospital and complied with 1964 Helsinki declaration and its later amendments or comparable ethical standards.
- 7.Yang J, Zhang Y, Sun X, Gusdon AM, Song N, Chen L, Jiang G, Huang Y (2018) The prognostic value of multiorgan metastases in patients with non-small cell lung cancer and its variants: a SEER-based study. J Cancer Res Clin Oncol 144(9):1835–1842. https://doi.org/10.1007/s00432-018-2702-9 CrossRefGoogle Scholar
- 11.Ettinger DS, Wood DE, Akerley W, Bazhenova LA, Borghaei H, Camidge DR, Cheney RT, Chirieac LR, D’Amico TA, Demmy TL, Dilling TJ, Dobelbower MC, Govindan R, Grannis FW Jr, Horn L, Jahan TM, Komaki R, Krug LM, Lackner RP, Lanuti M, Lilenbaum R, Lin J, Loo BW Jr, Martins R, Otterson GA, Patel JD, Pisters KM, Reckamp K, Riely GJ, Rohren E, Schild SE, Shapiro TA, Swanson SJ, Tauer K, Yang SC, Gregory K, Hughes M, National Comprehensive Cancer Network (2015) Non-small cell lung cancer, Version 6.2015. J Natl Compr Cancer Netw 13(5):515–524CrossRefGoogle Scholar
- 12.Asamura H, Chansky K, Crowley J, Goldstraw P, Rusch VW, Vansteenkiste JF, Watanabe H, Wu YL, Zielinski M, Ball D, Rami-Porta R, International Association for the Study of Lung Cancer S, Prognostic Factors Committee ABM, Participating I (2015) The International Association for the Study of Lung Cancer Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming 8th edition of the TNM classification for lung cancer. J Thorac Oncol 10(12):1675–1684. https://doi.org/10.1097/jto.0000000000000678 CrossRefGoogle Scholar
- 18.Roberts N, Kloos B, Cassella M, Podgrabinska S, Persaud K, Wu Y, Pytowski B, Skobe M (2006) Inhibition of VEGFR-3 activation with the antagonistic antibody more potently suppresses lymph node and distant metastases than inactivation of VEGFR-2. Cancer Res 66(5):2650–2657. https://doi.org/10.1158/0008-5472.CAN-05-1843 CrossRefGoogle Scholar
- 19.Brown M, Assen FP, Leithner A, Abe J, Schachner H, Asfour G, Bago-Horvath Z, Stein JV, Uhrin P, Sixt M, Kerjaschki D (2018) Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice. Science 359(6382):1408–1411. https://doi.org/10.1126/science.aal3662 CrossRefGoogle Scholar
- 20.Pereira ER, Kedrin D, Seano G, Gautier O, Meijer EFJ, Jones D, Chin SM, Kitahara S, Bouta EM, Chang J, Beech E, Jeong HS, Carroll MC, Taghian AG, Padera TP (2018) Lymph node metastases can invade local blood vessels, exit the node, and colonize distant organs in mice. Science 359(6382):1403–1407. https://doi.org/10.1126/science.aal3622 CrossRefGoogle Scholar
- 23.Ohta Y, Oda M, Wu J, Tsunezuka Y, Hiroshi M, Nonomura A, Watanabe G (2001) Can tumor size be a guide for limited surgical intervention in patients with peripheral non-small cell lung cancer? Assessment from the point of view of nodal micrometastasis. J Thorac Cardiovasc Surg 122(5):900–906. https://doi.org/10.1067/mtc.2001.117626 CrossRefGoogle Scholar