Online first
Review paper
Published online: 2025-03-27
The role of lymphadenectomy in surgical treatment of lung cancer
Abstract
The role of different types of lymphadenectomies in the curative-intent treatment of lung cancer is still a matter of debate. The aim of this review was to summarize the aspects of anatomy of the lymphatic systems of the lung and mediastinum and lymph node dissection, that are most important from the practical point of view. Literature search of Medline and Embase databases was performed to identify relevant papers. Those providing data regarding anatomy of the lymphatic system of the lung and mediastinum and all aspects of lymph node dissection in patients with lung cancer were reviewed. References included in the selected papers were also checked for relevance to the subject of this review. Retrieved data were grouped according to the following sections: (1) anatomy of the lymphatic system of the lung and mediastinum, (2) prevalence and numbers of mediastinal lymph nodes, (3) classification systems of pulmonary and mediastinal lymph nodes, (4) technical aspects of curative-intent lymphadenectomy and (5) special considerations.
Keywords: lung cancersurgical treatmentlymph node dissectionmediastinumanatomy
References
- Kużdżał J. Przydatność rozszerzonej limfadenektomii śródpiersiowej z dostępu szyjnego w ocenie stopnia zaawansowania niedrobnokomórkowego raka płuca. Ed. 1. Akademia Medyczna w Warszawie, Warszawa 2006.
- Rouviere H. Les vaisseaux lymphatiques des poumons et les ganglions visceraux intrathoraciques. An Anat Pathol. 1929; 6: 113–158.
- Rouviere H. Anatomie des Lymphaticsde le Homme. Masson et Cie, Paris 1932.
- Lauweryns J. The blood and lymphatic microcirculation of the lung. Appleton, New York 1971.
- Okada Y, Ito M, Nagaishi Ch. Anatomical study of the pulmonary lymphatics. Lymphology. 1979; 12(3): 118–124.
- Leak LV. Lymphatic removal of fluids and particles in the mammalian lung. Environ Health Perspect. 1980; 35: 55–75.
- Leak LV, Jamuar MP. Ultrastructure of pulmonary lymphatic vessels. Am Rev Respir Dis. 1983; 128(2 Pt 2): S59–S65.
- ENGEL S. The origin of the pulmonary lymph system. Acta Anat (Basel). 1957; 29(3): 228–235.
- Riquet M, Hidden G, Debesse B. Direct lymphatic drainage of lung segments to the mediastinal nodes. J Thorac Cardiovasc Surg. 1989; 97(4): 623–632.
- Riquet M, Hidden G, Debesse B. The lymphatic drainage of the lungs into the thoracic duct in the mediastinum. Surg Radiol Anat. 1988; 10(2): 165–166.
- Riquet M, Barthes FL, Souilamas R, et al. Thoracic duct tributaries from intrathoracic organs. Ann Thorac Surg. 2002; 73(3): 892–899.
- Riquet M, Hidden G, Debesse B, et al. Abdominal nodal connexions of the lymphatics of the lung. Surg Radiol Anat. 1988; 10(3): 251–252.
- Riquet M, Etienne G, Debesse B, et al. Direct metastasis to abdominal lymph nodes in bronchogenic carcinoma. J Thorac Cardiovasc Surg. 1990; 100(1): 153–154.
- Greenberg HB. Benign subpleural lymph node appearing as a pulmonary "coin" lesion. Radiology. 1961; 77: 97–99.
- Houk VN, Osborne DP, Houk VN, et al. Subvisceral pleural lymph node presenting as an expanding intrapulmonary nodule. Am Rev Respir Dis. 1965; 91: 596–9.
- Ehrenstein FI, Ehrenstein FI. Pulmonary lymph node presenting as an enlarging coin lesion. Am Rev Respir Dis. 1970; 101: 595–9.
- Kradin RL, Spirn PW, Mark EJ, et al. Intrapulmonary lymph nodes. Clinical, radiologic, and pathologic features. Chest. 1985; 87(5): 662–667.
- Borrie J. Lung Cancer: Surgery and Survival. Appleton, Ney York 1965.
- Borrie J. Primary carcinoma of the bronchus; prognosis following surgical resection; a clinico-pathological study of 200 patients. Ann R Coll Surg Engl. 1952; 10(3): 165–186.
- Nohl HC. An investigation into the lymphatic and vascular spread of carcinoma of the bronchus. Thorax. 1956; 11(3): 172–185.
- Nohl-Oser HC. An investigation of the anatomy of the lymphatic drainage of the lungs as shown by the lymphatic spread of bronchial carcinoma. Ann R Coll Surg Engl. 1972; 51(3): 157–176.
- Naruke T, Suemasu K, Ishikawa S, et al. Lymph node mapping and curability at various levels of metastasis in resected lung cancer. J Thorac Cardiovasc Surg. 1978; 76(6): 832–839.
- Tisi G, Friedman P, Peters R, et al. American Thoracic Society, Medical section of the American Lung Association. Clinical staging of primary lung cancer. Am Rev of Respir Dis. 1983; 127(5): 659–664.
- Mountain CF, Dresler CM, Mountain CF, et al. Regional lymph node classification for lung cancer staging. Chest. 1997; 111(6): 1718–1723.
- Groome PA, Bolejack V, Crowley JJ, et al. IASLC International Staging Committee, Cancer Research and Biostatistics, Observers to the Committee, Participating Institutions, IASLC International Staging Committee, Cancer Research and Biostatistics, Observers to the Committee, Participating Institutions. The IASLC Lung Cancer Staging Project: validation of the proposals for revision of the T, N, and M descriptors and consequent stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol. 2007; 2(8): 694–705.
- Rami-Porta R, Rami-Porta R. International association for the study of lung cancer (IASLC). IASLC staging manual in thoracic oncology. North Fort Meyers, Editorial Rx Press. ; 2016.
- Asamura H. Staging Manual for Thoracic Oncology, 3rd Ed. https://www.iaslc.org/research-education/publications-resources-guidelines/staging-manual-thoracic-oncology-3rd-edition.
- Rusch VW, Asamura H, Watanabe H, et al. Members of IASLC Staging Committee, Members of IASLC Staging Committee. The IASLC lung cancer staging project: a proposal for a new international lymph node map in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. 2009; 4(5): 568–577.
- Watanabe Si, Ladas G, Goldstraw P, et al. Inter-observer variability in systematic nodal dissection: comparison of European and Japanese nodal designation. Ann Thorac Surg. 2002; 73(1): 245–8; discussion 248.
- Riquet M, Manac'h D, Le Pimpec-Barthes F, et al. Prognostic significance of surgical-pathologic N1 disease in non-small cell carcinoma of the lung. Ann Thorac Surg. 1999; 67(6): 1572–1576.
- Asamura H, Suzuki K, Kondo H, et al. Where is the boundary between N1 and N2 stations in lung cancer? Ann Thorac Surg. 2000; 70(6): 1839–1846.
- Ueda K, Kaneda Y, Saeki K, et al. Hilar lymph nodes in N2 disease: survival analysis of patients with non-small cell lung cancers and regional lymph node metastasis. Surg Today. 2002; 32(4): 300–304.
- Riquet M, Le PiB, Riquet M, et al. Boundary between N1 and N2 stations in lung cancer: back to the future of anatomy. Ann Thorac Surg. 2001; 72: 1439–40.
- Beck E, Beattie EJ, Beck E, et al. Jr. The lymph nodes in the mediastinum. J Int Coll Surg. 1958; 29: 247–51.
- Genereux GP, Howie JL, Genereux GP, et al. Normal mediastinal lymph node size and number: CT and anatomic study. AJR Am J Roentgenol. 1984; 142(6): 1095–1100.
- Glazer GM, Gross BH, Quint LE, et al. Normal mediastinal lymph nodes: number and size according to American Thoracic Society mapping. AJR Am J Roentgenol. 1985; 144(2): 261–265.
- Kiyono K, Sone S, Sakai F, et al. The number and size of normal mediastinal lymph nodes: a postmortem study. AJR Am J Roentgenol. 1988; 150(4): 771–776.
- Trybalski Ł, Szadurski J, Zhang L, et al. Prevalence and quantity of lymph nodes at mediastinal stations in patients with lung cancer: lessons from 181 bilateral mediastinal lymphadenectomies. J Cardiothorac Surg. 2024; 19(1): 412.
- Sagawa M, Sato M, Sakurada A, et al. A prospective trial of systematic nodal dissection for lung cancer by video-assisted thoracic surgery: can it be perfect? Ann Thorac Surg. 2002; 73(3): 900–904.
- Watanabe A, Koyanagi T, Obama T, et al. Assessment of node dissection for clinical stage I primary lung cancer by VATS. Eur J Cardiothorac Surg. 2005; 27(5): 745–752.
- Zieliński M. Transcervical extended mediastinal lymphadenectomy: results of staging in two hundred fifty-six patients with non-small cell lung cancer. J Thorac Oncol. 2007; 2(4): 370–372.
- Brunn H. Surgical principles underlying one-stage lobectomy. Arch Surg. 1929; 18(1 part II): 490–515.
- Graham EA, Singer JJ, et al. Successful removal of an entire lung for carcinoma of the bronchus. CA Cancer J Clin. 1974; 24(4): 238–242.
- Cahan WG, Watson WL, Pool JL, et al. Radical pneumonectomy. J Thorac Surg. 1951; 22(5): 449–473.
- Ramsey HE, Cahan WG, Beattie EJ, et al. Radical lobectomy. J Thorac Cardiovasc Surg. 1960; 39(2): 555–572.
- Lardinois D, De Le, Van Sc, et al. Eur J Cardiothorac Surg. 2006; 30: 787–92.
- De Leyn P, Dooms C, Kuzdzal J, et al. Revised ESTS guidelines for preoperative mediastinal lymph node staging for non-small-cell lung cancer. Eur J Cardiothorac Surg. 2014; 45(5): 787–798.
- Ettinger DS, Akerley W, Borghaei H, et al. National comprehensive cancer network, National comprehensive cancer network. Non-small cell lung cancer, version 2.2013. J Natl Compr Canc Netw. 2013; 11(6): 645–53; quiz 653.
- Goldstraw P. International Association for the Study of Lung Cancer staging handbook in thoracic oncology. Editorial Rx Press, Florida, USA 2009.
- Howington JA, Blum MG, Chang AC, et al. Treatment of stage I and II non-small cell lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013; 143(5 Suppl): e278S–e313S.
- Handa Y, Tsutani Y, Mimae T, et al. Systematic versus lobe-specific mediastinal lymphadenectomy for hypermetabolic lung cancer. Ann Surg Oncol. 2021; 28(12): 7162–7171.
- Isaka M, Kojima H, Imai T, et al. Lobe-specific nodal dissection with intraoperative frozen section analysis for clinical stage-I non-small cell lung cancer: a validation study by propensity score matching. Gen Thorac Cardiovasc Surg. 2022; 70(11): 977–984.
- Handa Y, Tsutani Y, Mimae T, et al. Appropriate extent of lymphadenectomy in segmentectomy: a multicenter study. Jpn J Clin Oncol. 2021; 51(3): 451–458.
- Ramnath N, Dilling TJ, Harris LJ, et al. Chest Supplement Diagnosis and Management of Lung Cancer, 3rd Ed: ACCP Guidelines, Treatment of Stage III Non-small Cell Lung Cancer. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Published online. 2013.
- Wu YC, Lin CF, Hsu WH, et al. Long-term results of pathological stage I non-small cell lung cancer: Validation of using the number of totally removed lymph nodes as a staging control. Eur J Cardiothorac Surg. 2003; 24: 994–1001.
- Hata E, Hayakawa K, Miyamoto H, et al. Rationale for extended lymphadenectomy for lung cancer. Theor Surg. 1990; 5: 19–25.
- Sakao Y, Miyamoto H, Yamazaki A, et al. Prognostic significance of metastasis to the highest mediastinal lymph node in nonsmall cell lung cancer. Ann Thorac Surg. 2006; 81: 292–297.
- Hata E, Miyamoto H, Sakao Y, et al. Investigation into mediastinal lymph node metastasis of lung cancer and rationale for decision of the extent of mediastinal dissection. Nihon Geka Gakkai Zasshi. 1997; 98(1): 8–15.
- Sakaguchi H, Ikeda S, Kawano R, et al. Surgical treatment of N2 involved non-small cell lung cancer - the systematic extended lymph node dissection based on the regional lymphatic drainage. Kyobu Geka. 1999; 52(11): 901–905.
- Kużdżał J, Trybalski Ł, Hauer Ł, et al. Influence of bilateral mediastinal lymph node dissection on survival in non-small cell lung cancer patients - Randomized study. Lung Cancer. 2021; 156: 140–146.
- Wang W, Chen D, Xi K, et al. Impact of different types of lymphadenectomy combined with different extents of tumor resection on survival outcomes of stage i non-small-cell lung cancer: a large-cohort real-world study. Front Oncol. 2019; 9: 642.
- Ruffini E, Fang W, Guerrera F, et al. Staging and prognostic factors committee; staging and prognostic factors-thymic domain subcommittee; staging and prognostic factors subcommittees; members of the advisory boards. The international association for the study of lung cancer thymic tumors staging project: the impact of the eighth edition of the union for international cancer control and american joint committee on cancer TNM stage classification of thymic tumors. J Thorac Oncol. 2020; 15: 436–447.
- Sun J, Wu S, Jin Z, et al. Lymph node micrometastasis in non-small cell lung cancer. Biomed Pharmacother. 2022; 149: 112817.
- Zhao J, Li J, Li N, et al. Clinical significance of skipping mediastinal lymph node metastasis in N2 non-small cell lung cancer. J Thorac Dis. 2018; 10(3): 1683–1688.
- Wang Z, Cheng J, Huang W, et al. Skip metastasis in mediastinal lymph node is a favorable prognostic factor in N2 lung cancer patients: a meta-analysis. Ann Transl Med. 2021; 9(3): 218.
- Riquet M, Assouad J, Bagan P, et al. Skip mediastinal lymph node metastasis and lung cancer: a particular N2 subgroup with a better prognosis. Ann Thorac Surg. 2005; 79(1): 225–233.
- Zhang X, Ma Li, Xue M, et al. Advances in lymphatic metastasis of non-small cell lung cancer. Cell Commun Signal. 2024; 22(1): 201.
- Park JK, Moon Y, Park JK, et al. Prognosis of upstaged N1 and N2 disease after curative resection in patients with clinical N0 non-small cell lung cancer. J Thorac Dis. 2019; 11(4): 1202–1212.
- Zeng L, He T, Hu J, et al. Minimally invasive thoracic surgery: robot-assisted versus video-assisted thoracoscopic surgery. Wideochir Inne Tech Maloinwazyjne. 2023; 18(3): 436–444.
- Zimmermann J, Walter J, Pfeiffer V, et al. Propensity score matched comparison of lymph node upstaging in early-stage lung cancer: open versus minimally invasive surgery with standardized lymphadenectomy. J Cardiothorac Surg. 2025; 20(1): 96.