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

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. https://www.meta-analysis-made-easy.com). 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 I-2 = 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.