Mediastinal staging: when and how?

  • Antonio D’AndrilliEmail author
  • Giulio Maurizi
  • Federico Venuta
  • Erino A. Rendina
Special Edition Diagnosis and Treatment for Early Stage Non-small Cell Lung Cancer


Mediastinal staging for lung cancer includes both the assessment of mediastinal lymph nodes status before treatment and the postoperative pathological staging obtained by lymph-node removal performed during surgery. In patients with early stage NSCLC, the aim is to exclude with the highest certainty and the lowest morbidity the presence of mediastinal node involvement. Before treatment, mediastinal staging is based on imaging techniques, endoscopic techniques, and surgical procedures. Final pathological staging is based on lymph-node removal performed with lung resection according with different modalities (sampling, systematic dissection, etc.) and various approaches (thoracotomy, VATS, robotic). Data and indications from literature evidences are reported and discussed.


Lung cancer Mediastinal lymph nodes Staging 


Compliance with ethical standards

Conflict of interest

A. D’Andrilli received lecture fee from Baxter. G. Maurizi, F. Venuta, and E.A. Rendina declare no conflict of interest.


  1. 1.
    D’Andrilli A, Venuta F, Rendina EA. The role of lymphadenectomy in lung cancer surgery. Thorac Surg Clin. 2012;22(2):227–37.PubMedCrossRefGoogle Scholar
  2. 2.
    Osarogiagbon RU, Lee YS, Faris NR, Ray MA, Ojeabulu PO, Smeltzer MP. Invasive mediastinal staging for resected non-small cell lung cancer in a population-based cohort. J Thorac Cardiovasc Surg. 2019;158(4):1220–9.PubMedCrossRefGoogle Scholar
  3. 3.
    Silvestri GA, Gonzalez AV, Jantz MA, Margolis ML, Gould MK, Tanoue LT, et al. Methods for staging 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):e211S–e250S250S.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    The American Thoracic Society and The European Respiratory Society. Pretreatement evaluation of non-small-cell lung cancer. Am J Respiratory Crit Care Med. 1997;156(1):320–32.CrossRefGoogle Scholar
  5. 5.
    De Leyn P, Doomsb C, Kuzdzalc J, Lardinois D, et al. Revised ESTS guidelines for preoperative mediastinal lymph node staging for non-small-cell lung cancer. Eur J Cardiothorac Surg. 2014;45:1–12.CrossRefGoogle Scholar
  6. 6.
    Miao H, Shaolei L, Nan L, Yumei L, Shanyuan Z, Fangliang L, Yue Y. Occult mediastinal lymph node metastasis in FDG-PET/CT node-negative lung adenocarcinoma patients: risk factors and histopathological study. Thorac Cancer. 2019;10(6):1453–60.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Wang J, Welch K, Wang L, Kong FM. Negative predictive value of positron emission tomography and computed tomography for stage T1–2N0 non-small-cell lung cancer: a meta-analysis. Clin Lung Cancer. 2012;13(2):81–9.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Lee PC, Port LC, Korst RJ, Liss Y, Meherally DN, Altorki NK. Risk factors for occult mediastinal metastases in clinical stage I non-small cell lung cancer. Ann Thorac Surg. 2007;84(1):177–81.PubMedCrossRefGoogle Scholar
  9. 9.
    Hishida T, Yoshida J, Nishimura M, Nishiwaki Y, Nagai K. Problems in the current diagnostic standards of clinical N1 non-small cell lung cancer. Thorax. 2008;63(6):526–31.PubMedCrossRefGoogle Scholar
  10. 10.
    Wu LM, Xu JR, Gu HY, Hua J, Chen J, Zhang W, et al. Preoperative mediastinal and hilar nodal staging with diffusion-weighted magnetic resonance imaging and fluorodeoxyglucose positron emission omography/computed tomography in patients with non-small-cell lung cancer: which is better? J Surg Res. 2012;178(1):304–14.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Garpestad E, Goldberg S, Herth F, Garland R, LoCicero J 3rd, Thurer R, et al. CT fluoroscopy guidance for transbronchial needle aspiration: an experience in 35 patients. Chest. 2001;119(2):329–32.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Vilmann P, Frost Clementsen P, Colella S, Siemsen M, De Leyn P, Dumonceau JM, et al. Combined endobronchial and esophageal endosonography for the diagnosis and staging of lung cancer: European Society of Gastrointestinal Endoscopy (ESGE) Guideline, in cooperation with the European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS). Eur J Cardiothorac Surg. 2015;48(1):1–15.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    von Bartheld MB, Versteegh MI, Braun J, Willems LN, Rabe KF, Annema JT. Transesophageal ultrasound-guided fine-needle aspiration for the mediastinal restaging of non-small cell lung cancer. J Thorac Oncol. 2011;6(9):1510–5.CrossRefGoogle Scholar
  14. 14.
    Lee HS, Lee GK, Lee HS, Kim MS, Lee JM, Kim HY, et al. Real-time endobronchial ultrasound-guided transbronchial needle aspiration in mediastinal staging of non-small cell lung cancer: how many aspirations per target lymph node station? Chest. 2008;134(2):368–74.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Annema JT, Meerbeeck JP, Rintoul RC, Dooms C, Deschepper E, Dekkers OM, et al. Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: a randomized trial. JAMA. 2010;304(20):2245–52.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Yasufuku K, Pierre A, Darling G, de Perrot M, Waddell T, Johnston M, et al. A prospective controlled trial of endobronchial ultrasound-guided transbronchial needle aspiration compared with mediastinoscopy for mediastinal lymph node staging of lung cancer. J Thorac Cardiovasc Surg. 2011;142(6):1393–400.PubMedCrossRefPubMedCentralGoogle Scholar
  17. 17.
    Wallace MB, Pascual JM, Raimondo M, et al. Minimally invasive endoscopic staging of suspected lung cancer. JAMA. 2008;299(5):540–6.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Adams K, Shah PL, Edmonds L, Lim E. Test performance of endobronchial ultrasound and transbronchial needle aspiration biopsy for mediastinal staging in patients with lung cancer: systematic review and meta-analysis. Thorax. 2009;64(9):757–62.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Chandra S, Nehra M, Agarwal D, Mohan A. Diagnostic accuracy of endobronchial ultrasound-guided transbronchial needle biopsy in mediastinal lymphadenopathy: a systematic review and meta-analysis. Respir Care. 2012;57(3):384–91.PubMedPubMedCentralGoogle Scholar
  20. 20.
    Zhang R, Ying K, Shi L, Zhang L, Zhou L. Combined endobronchial and endoscopic ultrasound-guided fine needle aspiration for mediastinal lymph node staging of lung cancer: a meta-analysis. Eur J Cancer. 2013;49(8):1860–7.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Bousema JE, van Dorp M, Noyez VJJM, Dijkgraaf MGW, Annema JT, van den Broek FJC. Unforeseen N2 disease after negative endosonography findings with or without confirmatory mediastinoscopy in resectable non-small cell lung cancer: a systematic review and meta-analysis. J Thorac Oncol. 2019;14(6):979–92.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Gu P, Zhao YZ, Jiang LY, Zhang W, Xin Y. Endobronchial ultrasound-guided transbronchial needle aspiration for staging of lung cancer: a systematic review and meta-analysis. Eur J Cancer. 2009;45(8):1389–96.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Cho JH, Kim J, Kim K, Choi YS, Kim HK, Shim YM. A comparative analysis of video-assisted mediastinoscopy and conventional mediastinoscopy. Ann Thorac Surg. 2011;92(3):1007–111.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Zakkar M, Tan C, Hunt I. Is video mediastinoscopy a safer and more effective procedure than conventional mediastinoscopy? Interact Cardiovasc Thorac Surg. 2012;14(1):81–4. Scholar
  25. 25.
    Cerfolio RJ, Bryant AS, Eloubeidi MA. Accessing the aortopulmonary window (#5) and the paraaortic (#6) lymph nodes in patients with non-small cell lung cancer. Ann Thorac Surg. 2007;84(3):940–5.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Sebastián-Quetglás F, Molins L, Baldó X, Buitrago J, Vidal G, Spanish Video-assisted Thoracic Surgery Study Group. Clinical value of video-assisted thoracoscopy for preoperative staging of non-small cell lung cancer. A prospective study of 105 patients. Lung Cancer. 2003;42(3):297–301.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Rendina EA, Venuta F, De Giacomo T, Moretti MS, Ibrahim M, Coloni GF. Biopsy of anterior mediastinal masses under local anesthesia. Ann Thorac Surg. 2002;74(5):1720–2.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    D’Andrilli A, Venuta F, Rendina EA. Surgical approaches for invasive tumors of the anterior mediastinum. Thorac Surg Clin. 2010;20(2):265–84.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Hürtgen M, Friedel G, Toomes H, Fritz P. Radical video-assisted mediastinoscopic lymphadenectomy (VAMLA)—technique and first results. Eur J Cardiothorac Surg. 2002;21(2):348–51.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Kuzdzał J, Zieliński M, Papla B, Szlubowski A, Hauer Ł, Nabiałek T, et al. Transcervical extended mediastinal lymphadenectomy—the new operative technique and early results in lung cancer staging. Eur J Cardiothorac Surg. 2005;27(3):384–90.PubMedCrossRefGoogle Scholar
  31. 31.
    Witte B, Wolf M, Huertgen M, Toomes H. Video-assisted mediastinoscopic surgery: clinical feasibility and accuracy of mediastinal lymph node staging. Ann Thorac Surg. 2006;82(5):1821–7.PubMedCrossRefGoogle Scholar
  32. 32.
    De Leyn P, Stroobants S, De Wever W, Lerut T, Coosemans W, Decker G, et al. Prospective comparative study of integrated positron emission tomography-computed tomography scan compared with remediastinoscopy in the assessment of residual mediastinal lymph node disease after induction chemotherapy for mediastinoscopy-proven stage IIIA-N2 Non-small-cell lung cancer: a Leuven Lung Cancer Group Study. J Clin Oncol. 2006;24(21):3333–9.PubMedCrossRefGoogle Scholar
  33. 33.
    D’Andrilli A, Venuta F, Rendina EA. Resection for patients initially diagnosed with N3 after response to induction therapy. In: Ferguson MK, editor. Difficult decisions in thoracic surgery: an evidence-based approach. New York: Springer; 2007. p. 128–139.CrossRefGoogle Scholar
  34. 34.
    Cerfolio RJ, Bryant AS, Ojha B. Restaging patients with N2 (stage IIIa) non-small cell lung cancer after neoadjuvant chemoradiotherapy: a prospective study. J Thorac Cardiovasc Surg. 2006;131(6):1229–355.PubMedCrossRefGoogle Scholar
  35. 35.
    Herth F, Annema J, Eberhardt R, Yasufuku K, Ernst A, Krasnik M. Endobronchial ultrasound with transbronchial needle aspiration for restaging the mediastinum in lung cancer. J Clin Oncol. 2008;26:3346–50.PubMedCrossRefGoogle Scholar
  36. 36.
    Szlubowski A, Zielinski A, Soja J, Annema J, Sosnicki W, Jakubiak M, et al. A combined approach of endobronchial and endoscopic ultrasound-guided needle aspiration in the radiologically normal mediastinum in non-small-cell lung cancer staging—a prospective trial. Eur J Cardiothorac Surg. 2010;37:1175–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Stigt JA, Oostdijk AH, Timmer PR, Shahin GM, Boers JE, Groen HJ. Comparison of EUS-guided fine needle aspiration and integrated PET-CT in restaging after treatment for locally advanced non-small cell lung cancer. Lung Cancer. 2009;66(2):198–204.PubMedCrossRefGoogle Scholar
  38. 38.
    Stamatis G, Fechner S, Hillejan L, Hinterthaner M, Krbek T. Repeat mediastinoscopy as a restaging procedure. Pneumologie. 2005;59(12):862–6.PubMedCrossRefGoogle Scholar
  39. 39.
    Lardinois D, Schallberger A, Betticher D, Ris HB. Postinduction video-mediastinoscopy is as accurate and safe as video-mediastinoscopy in patients without pretreatment for potentially operable non-small cell lung cancer. Ann Thorac Surg. 2003;75(4):1102–6.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Jaklitsch MT, Gu L, Demmy T, Harpole DH, D'Amico TA, McKenna RJ, et al. Prospective phase II trial of preresection thoracoscopic mediastinal restaging after neoadjuvant therapy for IIIA (N2) non-small cell lung cancer: results of CALGB protocol 39803. J Thorac Cardiovasc Surg. 2013;146(1):9–16.PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Zielinski M, Szlubowski A, Kołodziej M, Orzechowski S, Laczynska E, Pankowski J, et al. Comparison of endobronchial ultrasound and/or endoesophageal ultrasound with transcervical extended mediastinal lymphadenectomy for staging and restaging of non-small-cell lung cancer. J Thorac Oncol. 2013;8(5):630–6.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Goldstaw P. International association for the study of lung cancer handbook in thoracic oncology. Florida: Editorial Rx Press; 2009.Google Scholar
  43. 43.
    Keller SM, Adak S, Wagner H, Johnson DH. Mediastinal lymph node dissection improves survival in patients with stages II and IIIa non-small cell lung cancer. Eastern Cooperative Oncology Group. Ann Thorac Surg. 2000;70(2):358–65.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Izbicki JR, Thetter O, Habekost M, et al. Radical systematic mediastinal lymphadenectomy in non-small cell lung cancer: a randomized controlled trial. Br J Surg. 1994;81:229.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Sugi K, Nawata K, Fujita N, Ueda K, Tanaka T, Matsuoka T, et al. Systematic lymph node dissection for clinically diagnosed peripheral non-small-cell lung cancer less than 2 cm in diameter. World J Surg. 1998;22(3):290–4.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Wu Y, Huang ZF, Wang SY, Yang XN, Ou W. A randomized trial of systematic nodal dissection in resectable non-small cell lung cancer. Lung Cancer. 2002;36(1):1–6.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Massard G, Ducrocq X, Kochetkova EA, Porhanov VA, Riquet M. Sampling or node dissection for intraoperative staging of lung cancer: a multicentric cross-sectional study. Eur J Cardiothorac Surg. 2006;30(1):164–7.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Gajra A, Newman N, Gamble GP, Kohman LJ, Graziano SL. Effect of number of lymph nodes sampled on outcome in patients with stage I non-small-cell lung cancer. J Clin Oncol. 2003;21(6):1029–34.PubMedCrossRefGoogle Scholar
  49. 49.
    Darling GE, Allen MS, Decker PA, Ballman K, Malthaner RA, Inculet RI, et al. 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. J Thorac Cardiovasc Surg. 2011;141(3):662–70.PubMedPubMedCentralCrossRefGoogle Scholar
  50. 50.
    Allen MS, Darling G, Pechet T, et al. Morbidity and mortality of major pulmonary resections in patients with early stage lung cancer: initial results of the randomized, prospective ACOSOG Z0030 trial. Ann Thorac Surg. 2006;81:1013–20.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Huang X, Wang J, Chen Q, Jiang J. Mediastinal lymph node dissection versus mediastinal lymph node sampling for early stage non-small cell lung cancer: a systematic review and meta-analysis. PLoS ONE. 2014;9(10):e109979.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Kneuertz PJ, Cheufou DH, D'Souza DM, Mardanzai K, Abdel-Rasoul M, Theegarten D, et al. Propensity-score adjusted comparison of pathologic nodal upstaging by robotic, video-assisted thoracoscopic, and open lobectomy for non-small cell lung cancer. J Thorac Cardiovasc Surg. 2019;158(5):1457–66.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© The Japanese Association for Thoracic Surgery 2019

Authors and Affiliations

  • Antonio D’Andrilli
    • 1
    Email author
  • Giulio Maurizi
    • 1
  • Federico Venuta
    • 2
  • Erino A. Rendina
    • 1
  1. 1.Department of Thoracic SurgerySapienza University, Sant’Andrea HospitalRomeItaly
  2. 2.Department of Thoracic SurgerySapienza UniversityRomeItaly

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