After Cahan’s first description of radical mediastinal lymphadenectomy in 1951,  complete mediastinal lymph node dissection for non-small cell lung cancer (NSCLC) remained a controversial procedure. The procedure was found to provide optimal staging for resectable NSCLC, but its therapeutic value continued to be debated. One study reported that only 57.3% of patients had any mediastinal nodes removed at the time of pulmonary resection. 
Accurate pretreatment staging of mediastinal lymph nodes in lung cancer is essential to determining prognosis and treatment because patients with involved mediastinal lymph nodes may not benefit from upfront surgical resection. Computed tomography (CT) and positron emission tomography (PET) lack both sensitivity and specificity for accurate lymph node staging. Transbronchial and esophageal needle aspiration provide specificity, but technical constraints hamper sensitivity.
Surgical mediastinoscopy is the pretherapeutic staging maneuver with the highest sensitivity and specificity, but it is dependent on the number of lymph nodes sampled and has technical limitations, especially for left-upper-lobe tumors. Additionally, the lymphatic system of the lungs has substantial anatomic variability, and skip metastasis can be found in 25% of cases.  Thus, a significant number of patients who undergo surgical resection of their lung cancer may harbor positive mediastinal lymph nodes.
A mediastinal lymphadenectomy may be performed to achieve complete staging (possibly to make postoperative treatment decisions), better locoregional control, and improved overall survival. Arguments against the procedure include increased operating time, possible increased morbidity, and lack of conclusive evidence to support an increased survival rate from the procedure.
The results of the American College of Surgeons Oncology Group (ACOSOG) Z0030 study suggested that complete mediastinal lymphadenectomy does not improve survival for early-stage NSCLC. However, in this trial, complete dissection was compared with rigorous systematic sampling. Thus, surgeons adhering to the highest standards of complete lung cancer staging should continue to perform thorough mediastinal lymph node sampling.
There is growing acceptance of video-assisted thoracoscopic surgery (VATS) in the surgical treatment of early-stage lung cancer. The difficulty in performing a mediastinal lymphadenectomy thoracoscopically may affect the continued use of this procedure. The statement made by Robert Ginsberg in 1997 remains true today: “The addition of mediastinal lymph node dissection produces the best possible surgical and pathologic staging of lymph node disease but has yet to be proven more efficacious as a curative procedure.” 
Complete mediastinal lymphadenectomy will continue to be performed in medical centers demanding the most comprehensive information. This is justified by previous data demonstrating that the dissection can be performed with minimal time and no increase in morbidity and mortality.
For centers pursuing minimally invasive techniques, VATS mediastinal lymph node staging and video-assisted mediastinal lymphadenectomy (VAMLA) are clinically feasible procedures with accurately staging and acceptable complication rate. Academic medical centers with the infrastructure and experience will provide the data needed validate the application of noninvasive techniques to optimally stage and ultimately treat patients with NSCLC.
Mediastinal lymphadenectomy is indicated for T1-3 N0-1 resectable NSCLC. Patients should be without evidence of mediastinal lymph node involvement as assessed by preoperative imaging (CT, PET, or both) and sampling by means of mediastinoscopy, a Chamberlain procedure, endoscopic ultrasonography (US), or a transbronchial technique.
A critical review of published literature on mediastinal lymphadenectomy requires an understanding of the described operative technique. Sampling refers to the technique of removing easily found and obviously abnormal mediastinal lymph nodes. Systematic sampling refers to the routine biopsy of lymph nodes at levels or stations as specified by the authors. Complete mediastinal lymph node dissection refers to the routine complete removal of all mediastinal tissue as described by the authors.
The classification of regional lymph node stations for lung cancer staging reported by Mountain and Dresler in 1997 describes the anatomic landmarks for 14 levels of intrapulmonary, hilar, and mediastinal lymph nodes stations.  TNM classification for lung cancer classifies lymph node stations into six zones, as follows:
N3 lymph nodes are contralateral mediastinal, ipsilateral scalene, or supraclavicular. Among the primary tumors that had only a single involved N2 station, the most common site of lymph node metastases was level 4R for right-upper-lobe tumors, levels 5/6 for left-upper-lobe tumors, and level 7 for middle- and lower-lobe tumors. 
Four published randomized trials compared mediastinal lymph node dissection and mediastinal lymph node sampling. [9, 10, 11, 12] A meta-analysis of the first three trials reported a survival advantage for stages I, II, and IIIA, and a fixed-effects model by the same group reported that mediastinal lymph node dissection reduced the risk of death. [13, 14]
In the multicenter, prospective, randomized ACOSOG Z0030 Trial,  median survival was 8.1 years for mediastinal lymph node sampling and 8.5 years for mediastinal lymph node dissections. The authors concluded that mediastinal lymph node dissection does not improve survival in patients with early-stage NSCLC, but results are not generalizable to patients staged radiographically or those with higher-stage tumors. Formal en-bloc mediastinal resection may still affect survival and certainly optimally stages patients who do not undergo rigorous preoperative (mediastinoscopy) and intraoperative (mediastinal lymph node sampling) procedures.
Call et al assessed the results of VAMLA for staging NSCLC in 160 cases, 138 of which involved clinical N0-1 cancers.  They found VAMLA to be highly accurate, with a sensitivity of 0.96 (95% confidence interval [CI], 0.81-99.3), a specificity of 1 (95% CI, 0.97-1), a positive predictive value of 1 (95% CI, 0.87-1), a negative predictive value of 0.99 (95% CI, 0.95-0.99), and a diagnostic accuracy of 0.99 (95% CI, 0.96-0.99). Complications developed in 5.9% of patients.
Wang et al retrospectively studied 712 consecutive cases of clinical N0-1 lung cancer (including 152 cases of pathologic N2 disease and 560 cases of pathologic N0-1 disease confirmed after surgery) to assess whether mediastinal lymphadenectomy compliant with National Comprehensive Cancer Network (NCCN) criteria (≥3 stations of N2 node dissection) improved oncologic outcomes in this group.  They found that such a lymphadenectomy was a significant prognostic factor for overall survival both in the cohort as a whole and the patients with pathologic N2 status; more extended N2 node dissection did not appear to improve outcome further in the latter.
CAHAN WG, WATSON WL, POOL JL. Radical pneumonectomy. J Thorac Surg. 1951 Nov. 22 (5):449-73. [Medline].
Little AG, Rusch VW, Bonner JA, Gaspar LE, Green MR, Webb WR, et al. Patterns of surgical care of lung cancer patients. Ann Thorac Surg. 2005 Dec. 80 (6):2051-6; discussion 2056. [Medline].
Hata E, Hayakawa K, Miyamoto H, et al. Rationale for extended lymphadenectomy for lung cancer. Theor Surg. 1990. 5:19-25.
Ginsberg RJ. Resection of non-small cell lung cancer: how much and by what route. Chest. 1997 Oct. 112 (4 Suppl):203S-205S. [Medline].
Yendamuri S, Battoo A, Dy G, Chen H, Gomez J, Singh AK, et al. Transcervical Extended Mediastinal Lymphadenectomy: Experience From a North American Cancer Center. Ann Thorac Surg. 2017 Nov. 104 (5):1644-1649. [Medline].
Mountain CF, Dresler CM. Regional lymph node classification for lung cancer staging. Chest. 1997 Jun. 111 (6):1718-23. [Medline].
Rusch VW, Crowley J, Giroux DJ, Goldstraw P, Im JG, Tsuboi M, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the N descriptors in the forthcoming seventh edition of the TNM classification for lung cancer. J Thorac Oncol. 2007 Jul. 2 (7):603-12. [Medline].
Izbicki JR, Passlick B, Pantel K, Pichlmeier U, Hosch SB, Karg O, et al. Effectiveness of radical systematic mediastinal lymphadenectomy in patients with resectable non-small cell lung cancer: results of a prospective randomized trial. Ann Surg. 1998 Jan. 227 (1):138-44. [Medline].
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 Mar. 22 (3):290-4; discussion 294-5. [Medline].
Wu Yl, 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 Apr. 36 (1):1-6. [Medline].
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 Mar. 141 (3):662-70. [Medline].
Wright G, Manser RL, Byrnes G, Hart D, Campbell DA. Surgery for non-small cell lung cancer: systematic review and meta-analysis of randomised controlled trials. Thorax. 2006 Jul. 61 (7):597-603. [Medline].
Manser R, Wright G, Hart D, Byrnes G, Campbell DA. Surgery for early stage non-small cell lung cancer. Cochrane Database Syst Rev. 2005 Jan 25. CD004699. [Medline].
Call S, Obiols C, Rami-Porta R, Trujillo-Reyes JC, Iglesias M, Saumench R, et al. Video-Assisted Mediastinoscopic Lymphadenectomy for Staging Non-Small Cell Lung Cancer. Ann Thorac Surg. 2016 Apr. 101 (4):1326-33. [Medline].
Wang X, Yan S, Phan K, Yan TD, Zhang L, Yang Y, et al. Mediastinal lymphadenectomy fulfilling NCCN criteria may improve the outcome of clinical N0-1 and pathological N2 non-small cell lung cancer. J Thorac Dis. 2016 Mar. 8 (3):342-9. [Medline]. [Full Text].
Naruke T. Mediastinal lymph node dissection. General Thoracic Surgery. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2005.
Martini N. Mediastinal lymph node dissection for lung cancer. The Memorial experience. Chest Surg Clin N Am. 1995 May. 5 (2):189-203. [Medline].
Watanabe Y, Shimizu J, Tsubota M, Iwa T. Mediastinal spread of metastatic lymph nodes in bronchogenic carcinoma. Mediastinal nodal metastases in lung cancer. Chest. 1990 May. 97 (5):1059-65. [Medline].
Whitson BA, Groth SS, Duval SJ, Swanson SJ, Maddaus MA. Surgery for early-stage non-small cell lung cancer: a systematic review of the video-assisted thoracoscopic surgery versus thoracotomy approaches to lobectomy. Ann Thorac Surg. 2008 Dec. 86 (6):2008-16; discussion 2016-8. [Medline].
Yan TD, Black D, Bannon PG, McCaughan BC. Systematic review and meta-analysis of randomized and nonrandomized trials on safety and efficacy of video-assisted thoracic surgery lobectomy for early-stage non-small-cell lung cancer. J Clin Oncol. 2009 May 20. 27 (15):2553-62. [Medline].
Allakhverdiev A, Davydov M, Akhmedov P. Thoracoscopic lobectomy with mediastinal lymph node dissection as a standard surgery for T1-2N0M0 non-small cell lung cancer (>300 surgeries experience). Ann Med Surg (Lond). 2018 Nov. 35:169-172. [Medline]. [Full Text].
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 Sep. 84 (3):940-5. [Medline].
Hürtgen M, Friedel G, Toomes H, Fritz P. Radical video-assisted mediastinoscopic lymphadenectomy (VAMLA)–technique and first results. Eur J Cardiothorac Surg. 2002 Feb. 21 (2):348-51. [Medline].
Leschber G, Holinka G, Linder A. Video-assisted mediastinoscopic lymphadenectomy (VAMLA)–a method for systematic mediastinal lymphnode dissection. Eur J Cardiothorac Surg. 2003 Aug. 24 (2):192-5. [Medline].
Witte B, Messerschmidt A, Hillebrand H, Gross S, Wolf M, Kriegel E, et al. Combined videothoracoscopic and videomediastinoscopic approach improves radicality of minimally invasive mediastinal lymphadenectomy for early stage lung carcinoma. Eur J Cardiothorac Surg. 2009 Feb. 35 (2):343-7. [Medline].
Yoo DG, Kim YH, Kim DK, Kim HR, Park SI. Clinical feasibility and surgical benefits of video-assisted mediastinoscopic lymphadenectomy in the treatment of resectable lung cancer. Eur J Cardiothorac Surg. 2011 Dec. 40 (6):1483-6. [Medline].
Zhang J, Wu Y, Li H, Shen Q, Yu C, Chai Y. Retrospective study on video-assisted vs. open mediastinal lymphadenectomy for non-small cell lung cancer: a propensity-matched analysis. J Thorac Dis. 2018 Mar. 10 (3):1884-1890. [Medline]. [Full Text].
R James Koness, MD, FACS Program Director, Fellowship in Surgical Oncology, Roger Williams Medical Center; Clinical Assistant Professor, Division of Surgical Oncology, Department of Surgery, The Warren Alpert Medical School of Brown University
R James Koness, MD, FACS is a member of the following medical societies: American College of Surgeons, American Head and Neck Society, Society of Surgical Oncology, American Society of Breast Surgeons
Disclosure: Nothing to disclose.
N Joseph Espat, MD, MS, FACS Harold J Wanebo Professor of Surgery, Assistant Dean of Clinical Affairs, Boston University School of Medicine; Chairman, Department of Surgery, Director, Adele R Decof Cancer Center, Roger Williams Medical Center
N Joseph Espat, MD, MS, FACS is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Surgeons, American Medical Association, American Society for Parenteral and Enteral Nutrition, American Society of Clinical Oncology, Americas Hepato-Pancreato-Biliary Association, Association for Academic Surgery, Central Surgical Association, Chicago Medical Society, International Hepato-Pancreato-Biliary Association, Pancreas Club, Sigma Xi, Society for Leukocyte Biology, Society for Surgery of the Alimentary Tract, Society of American Gastrointestinal and Endoscopic Surgeons, Society of Surgical Oncology, Society of University Surgeons, Southeastern Surgical Congress, Southern Medical Association, Surgical Infection Society
Disclosure: Nothing to disclose.
Erik D Schraga, MD Staff Physician, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates
Disclosure: Nothing to disclose.
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