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      Investigation of mediastinal lymph node dissection in clinical stage IA pure-solid non-small cell lung cancer patients

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          Abstract

          Objective

          To explore the independent predictors of pathological mediastinal lymph node (pN2) metastasis in clinical stage IA (cIA) pure-solid non-small cell lung cancer (NSCLC) patients, and to find an appropriate method of mediastinal lymph node dissection.

          Methods

          This study retrospectively evaluated 533 cIA pure-solid NSCLC patients who underwent radical resection of lung cancer (lobectomy combined with systematic lymph node dissection) from January 2014 to December 2016. The relationship between clinicopathological characteristics and pN2 metastasis was analyzed, and the independent predictors of pN2 metastasis were determined by univariate and multivariate logistic regression analysis. We defined the new factor Y as composed of preoperative cT, CEA, and NSE.

          Results

          There were 72 cases (13.5%) of pN2 metastasis in cIA pure-solid NSCLC patients. Preoperative clinical tumor diameter (cT), serum CEA level, serum NSE level, and pathological status of station 10 lymph nodes were independent predictors of pN2 metastasis. Patients with cT ≤ 21.5 mm, CEA ≤ 3.85 ng/mL, NSE ≤ 13.40 ng/mL and negative station 10 lymph node group showed lower rates of pN2 metastasis. The new factor Y was an independent predictor of pN2 metastasis. Only 3 (2.1%) of 143 patients in the Y low-risk group showed pN2 metastasis.

          Conclusion

          For patients with low risk of pN2 metastasis, it might be feasible to take lobe-specific lymph node sampling or systematic lymph node sampling. As for those with high risk of pN2 metastasis, systematic lymph node dissection would be recommended.

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          Most cited references20

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          ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer.

          The European Society of Thoracic Surgeons (ESTS) organized a workshop dealing with lymph node staging in non-small cell lung cancer. The objective of this workshop was to develop guidelines for definitions and the surgical procedures of intraoperative lymph node staging, and the pathologic evaluation of resected lymph nodes in patients with non-small cell lung cancer (NSCLC). Relevant peer-reviewed publications on the subjects, the experience of the participants, and the opinion of the ESTS members contributing on line, were used to reach a consensus. Systematic nodal dissection is recommended in all cases to ensure complete resection. Lobe-specific systematic nodal dissection is acceptable for peripheral squamous T1 tumors, if hilar and interlobar nodes are negative on frozen section studies; it implies removal of, at least, three hilar and interlobar nodes and three mediastinal nodes from three stations in which the subcarinal is always included. Selected lymph node biopsies and sampling are justified to prove nodal involvement when resection is not possible. Pathologic evaluation includes all lymph nodes resected separately and those remaining in the lung specimen. Sections are done at the site of gross abnormalities. If macroscopic inspection does not detect any abnormal site, 2-mm slices of the nodes in the longitudinal plane are recommended. Routine search for micrometastases or isolated tumor cells in hematoxylin-eosin negative nodes would be desirable. Randomized controlled trials to evaluate adjuvant therapies for patients with these conditions are recommended. The adherence to these guidelines will standardize the intraoperative lymph node staging and pathologic evaluation, and improve pathologic staging, which will help decide on the best adjuvant therapy.
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            Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non-small cell carcinoma: results of the American College of Surgery Oncology Group Z0030 Trial.

            To determine whether mediastinal lymph node dissection improves survival compared with mediastinal lymph node sampling in patients undergoing resection for N0 or nonhilar N1, T1, or T2 non-small cell lung cancer. Patients with non-small cell lung cancer underwent sampling of 2R, 4R, 7, and 10R for right-sided tumors and 5, 6, 7, and 10L for left-sided tumors. If all tumors were negative for malignancy, patients were randomized to no further lymph node sampling (mediastinal lymph node sampling) or complete mediastinal lymph node dissection. Of 1111 patients randomized, 1023 (mediastinal lymph node sampling in 498, mediastinal lymph node dissection in 525) were eligible and evaluable. There were no significant differences between the 2 groups in terms of demographics, Eastern Cooperative Oncology Group status, histology, cancer location, type or extent of resection, and pathologic stage. Occult N2 disease was found in 21 patients in the mediastinal lymph node dissection group. At a median follow-up of 6.5 years, 435 patients (43%) have died: mediastinal lymph node sampling in 217 (44%) and mediastinal lymph node dissection in 218 (42%). The median survival is 8.1 years for mediastinal lymph node sampling and 8.5 years for mediastinal lymph node dissection (P = .25). The 5-year disease-free survival was 69% (95% confidence interval, 64-74) in the mediastinal lymph node sampling group and 68% (95% confidence interval, 64-73) years in the mediastinal lymph node dissection group (P = .92). There was no difference in local (P = .52), regional (P = .10), or distant (P = .76) recurrence between the 2 groups. If systematic and thorough presection sampling of the mediastinal and hilar lymph nodes is negative, mediastinal lymph node dissection does not improve survival in patients with early stage non-small cell lung cancer, but these results are not generalizable to patients staged radiographically or those with higher stage tumors. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
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              Carcinoembryonic antigen, squamous cell carcinoma antigen, CYFRA 21-1, and neuron-specific enolase in squamous cell lung cancer patients.

              Carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC-Ag), and CYFRA 21-1 are the most useful markers for non-small cell lung cancer (NSCLC), but neuron-specific enolase (NSE) is a tumor maker of choice for SCLC. The determination of NSE in NSCLC could allow selection of patients with neuroendocrine features. NSCLC patients whose tumors have neuroendocrine properties may be more responsive to chemotherapy; however, these tumors have been reported to be more aggressive. Tumor markers are not suitable for diagnosis; their principal applications are in monitoring of therapy and prognosis. Tumor markers were measured in 200 untreated patients with squamous cell lung cancer (SQC) and a reference group (n = 220; 124 healthy persons and 96 patients with nonmalignant lung disease). CEA and SCC-Ag were measured by microparticle enzyme immunoassays on Abbott AxSYM and IMx analyzers. CYFRA 21-1 and NSE were measured by electrochemiluminescence immunoassays on the Roche Elecsys 2010. CEA, SCC-Ag, CYFRA 21-1, and NSE were increased above the cutoffs in 26%, 32%, 67%, and 28% of tested patients, respectively. The area under the ROC curve for CYFRA 21-1 was higher than those for CEA, SCC-Ag, and NSE (SQC vs controls). CYFRA 21-1 and CEA were significantly higher in advanced SQC than in early stages of disease (P <0.0001 and P <0.0004, respectively). In multivariate analysis of survival, CYFRA 21-1 was an independent but nonspecific prognostic factor in the operable group of SQC patients, whereas NSE was an independent prognostic factor in the advanced stages of disease. CYFRA 21-1 is an independent prognostic factor in earlier stages and NSE in the advanced stages of SQC.
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                Author and article information

                Contributors
                2106@hrbmu.edu.cn
                Journal
                J Cardiothorac Surg
                J Cardiothorac Surg
                Journal of Cardiothoracic Surgery
                BioMed Central (London )
                1749-8090
                24 June 2024
                24 June 2024
                2024
                : 19
                : 357
                Affiliations
                Department of Thoracic Surgery, Harbin Medical University Cancer Hospital, ( https://ror.org/01f77gp95) No.150, Haping Rd., Nangang District, Harbin, Heilongjiang Province 150081 China
                Article
                2839
                10.1186/s13019-024-02839-z
                11194863
                38910251
                9a8057c6-8f22-49ac-a82f-f998ac8ceed0
                © The Author(s) 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 10 January 2024
                : 14 June 2024
                Funding
                Funded by: Individualized and precise treatment of lung cancer
                Award ID: Nn10py2017-04
                Award ID: Nn10py2017-04
                Award ID: Nn10py2017-04
                Award ID: Nn10py2017-04
                Award ID: Nn10py2017-04
                Award ID: Nn10py2017-04
                Categories
                Research
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2024

                Surgery
                non-small cell lung cancer,mediastinal lymph node,pure-solid nodule
                Surgery
                non-small cell lung cancer, mediastinal lymph node, pure-solid nodule

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