Prognostic Impact of Extracapsular Lymph Node Invasion on Survival in Non-small-Cell Lung Cancer: A Systematic Review and Meta-analysis

  • Seyed Vahid Tabatabaei
  • Christoph Nitche
  • Maximilian Michel
  • Kurt Rasche
  • Khosro Hekmat
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1116)


The extracapsular tumor extension (ECE) of nodal metastasis is an important prognostic factor in different types of malignancies. However, there is a lack of recent data in patients with non-small-cell lung cancer (NSCLC). In addition, the TNM staging system does not include ECE status as a prognostic factor. This systematic review and meta-analysis has been conducted to summarize and pool existing data to determine the prognostic role of ECE in patients with lymph node-positive NSCLC. Two authors performed an independent search in PubMed using a predefined keyword list, without language restrictions with publication date since 1990. Prospective or retrospective studies reporting data on prognostic parameters in subjects with NSCLC with positive ECE or with only intracapsular lymph node metastasis were retrieved. Data were summarized using risk ratios (RR) for the survival with 95% confidence intervals (CI). The data was analyzed using Mix 2 (ref: Bax L: MIX 2.0 – Professional software for meta-analysis in Excel. Version 2.015. BiostatXL, 2016. There 2,105 studies were reviewed. Five studies covering a total of 828 subjects met the inclusion criteria and were included in the meta-analysis. Two hundred and ninety-eight (35.9%) patients were categorized as ECE+, of whom 54 (18.1%) survived at the end of follow-up. In the ECE-negative group, 257 patients (48.4%) survived by the end of follow-up. Thus, ECE status is associated with a significantly decreased survival rate: pooled RR 0.45 (95% CI 0.35–0.59), Q(4) = 4.06, Pvalue = 0.39, and I2 = 68.00% (95 CI 0.00–79.55%). In conclusion, ECE has a significant impact on survival in NSCLC patients and should be considered in diagnostic and therapeutic decisions in addition to the current TNM staging. Postoperative radiotherapy may be an option in ECE-positive pN1 NSCLC patients.


Extracapsular lymph node invasion Meta-analysis Metastases Non-small-cell lung cancer Prognostic factor Survival rate 


Conflicts of Interests

The authors declare no conflicts of interest in relation to this article.


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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Seyed Vahid Tabatabaei
    • 1
  • Christoph Nitche
    • 2
  • Maximilian Michel
    • 3
  • Kurt Rasche
    • 1
  • Khosro Hekmat
    • 4
  1. 1.Department of Internal Medicine, Division of Pulmonary, Allergy, and Sleep Medicine, HELIOS Clinic WuppertalWitten/Herdecke UniversityWuppertalGermany
  2. 2.Department of Internal MedicineMarien Hospital Euskirchen, Teaching Hospital of Uniklinik BonnEuskirchenGermany
  3. 3.Institute of Zoology, University of CologneCologneGermany
  4. 4.Department of Cardiothoracic SurgeryUniversity Clinic of CologneCologneGermany

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