Surgical Assessment and Intraoperative Management of Mediastinal Lymph Nodes in Non-Small Cell Lung Cancer
2007; Elsevier BV; Volume: 84; Issue: 3 Linguagem: Inglês
10.1016/j.athoracsur.2007.04.032
ISSN1552-6259
AutoresBryan A. Whitson, Shawn S. Groth, Michael A. Maddaus,
Tópico(s)Lung Cancer Treatments and Mutations
ResumoMediastinal lymph node status has important prognostic and therapeutic implications for nonsmall cell lung cancer patients. Consequently, an accurate pathologic assessment of mediastinal lymph nodes for metastasis is essential. Despite the significance of nodal assessment, practice patterns among surgeons vary widely. Therefore we reviewed the literature to provide evidence-based recommendations regarding the ideal means and extent of preoperative and intraoperative pathologic mediastinal lymph node staging in non-small cell lung cancer patients. We found that the most sensitive and accurate intraoperative method is a complete mediastinal lymph node dissection. Pathologic evaluation of at least 10 mediastinal lymph node from at least three stations should be performed at the time of surgery. Mediastinal lymph node status has important prognostic and therapeutic implications for nonsmall cell lung cancer patients. Consequently, an accurate pathologic assessment of mediastinal lymph nodes for metastasis is essential. Despite the significance of nodal assessment, practice patterns among surgeons vary widely. Therefore we reviewed the literature to provide evidence-based recommendations regarding the ideal means and extent of preoperative and intraoperative pathologic mediastinal lymph node staging in non-small cell lung cancer patients. We found that the most sensitive and accurate intraoperative method is a complete mediastinal lymph node dissection. Pathologic evaluation of at least 10 mediastinal lymph node from at least three stations should be performed at the time of surgery. A critical determinant of survival in non-small cell lung cancer (NSCLC) patients is nodal status at the time of tumor staging [1Mountain C.F. Revisions in the International System for Staging Lung Cancer.Chest. 1997; 111: 1710-1717Crossref PubMed Scopus (4522) Google Scholar, 2Naruke T. Goya T. Tsuchiya R. Suemasu K. Prognosis and survival in resected lung carcinoma based on the new international staging system.J Thorac Cardiovasc Surg. 1988; 96: 440-447Abstract Full Text PDF PubMed Google Scholar]. However, the delineation of an adequate mediastinal lymph node (MLN) evaluation in NSCLC patients is controversial. As a result, practice patterns among surgeons vary widely.In 2001, the American College of Surgeons conducted a survey of the practice patterns of 729 United States tertiary teaching hospitals and community hospitals. The American College of Surgeons survey highlighted several areas that needed to be improved in the care of NSCLC patients and suggested that an abysmally low number of NSCLC patients in the United States undergo an adequate MLN assessment. Only 27.1% of patients underwent preoperative mediastinoscopy. Remarkably, of those patients who underwent mediastinoscopy, a MLN was identified by pathologic testing only 46.6% of the time [3Little A.G. Rusch V.W. Bonner J.A. et al.Patterns of surgical care of lung cancer patients.Ann Thorac Surg. 2005; 80: 2051-2056Abstract Full Text Full Text PDF PubMed Scopus (364) Google Scholar]. Furthermore, despite overwhelming evidence favoring pathologic staging of MLNs in NSCLC patients, only 57.8% of the patients overall had any nodes removed from the mediastinum at the time of surgical resection [3Little A.G. Rusch V.W. Bonner J.A. et al.Patterns of surgical care of lung cancer patients.Ann Thorac Surg. 2005; 80: 2051-2056Abstract Full Text Full Text PDF PubMed Scopus (364) Google Scholar]. Practice patterns of MLN evaluations differed depending on the type of institution where the operations were being performed. Highly significant differences (p < 0.01) were seen between the rates of MLN evaluations performed at academic institutions (67.9%), at community comprehensive cancer centers (55.6%), and at community cancer centers (48.1%) [3Little A.G. Rusch V.W. Bonner J.A. et al.Patterns of surgical care of lung cancer patients.Ann Thorac Surg. 2005; 80: 2051-2056Abstract Full Text Full Text PDF PubMed Scopus (364) Google Scholar].The differences in practice patterns may be due to inadequate training or a lag in communication, or both, and dissemination of evidence that favors a thorough MLN evaluation. Due to the prognostic and therapeutic implications of an accurate determination of mediastinal nodal status, we reviewed the literature to establish evidence-based recommendations for a sufficient clinical and pathologic MLN evaluation.MethodsWe performed a literature search using the PubMed database (ie, at www.pubmed.gov) of the National Library of Medicine and the National Institutes of Health. The following keywords and medical subject headings were analyzed to identify relevant studies: non-small cell lung cancer, lymph node (LN), mediastinum, mediastinal, sampling, dissection, surgery, and evaluation. We excluded articles focusing on disease processes other than NSCLC, as well as case reports.For this review, we categorized operative techniques for evaluating MLNs as a complete mediastinal lymph node dissection (MLND), a systematic mediastinal lymph node sampling (MLNS), or no defined evaluation. The location of MLNs was categorized according to the American Thoracic Society regional lymph node (LN) classification system [4Mountain C.F. Dresler C.M. Regional lymph node classification for lung cancer staging.Chest. 1997; 111: 1718-1723Crossref PubMed Scopus (1241) Google Scholar].Pathologic Staging of MLN: Operative ApproachesAlthough positron emission tomography and computed tomographic fusion scans are the most sensitive and accurate radiographic means of screening for MLN metastasis [5Cerfolio R.J. Ojha B. Bryant A.S. Raghuveer V. Mountz J.M. Bartoluci A.A. The accuracy of integrated PET-CT compared with dedicated PET alone for the staging of patients with nonsmall cell lung cancer.Ann Thorac Surg. 2004; 78: 1017-1023Abstract Full Text Full Text PDF PubMed Scopus (302) Google Scholar, 6Halpern B.S. Schiepers C. Weber W.A. et al.Presurgical staging of non-small cell lung cancer: positron emission tomography, integrated positron emission tomography/CT, and software image fusion.Chest. 2005; 128: 2289-2297Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar, 7Magnani P. Carretta A. Rizzo G. et al.FDG/PET and spiral CT image fusion for medistinal lymph node assessment of non-small cell lung cancer patients.J Cardiovasc Surg (Torino). 1999; 40: 741-748PubMed Google Scholar], clinical staging by imaging alone is not completely reliable. In a large, multi-institutional, cooperative group trial involving 502 patients, 38.3% of NSCLC were upstaged after a pathologic LN evaluation [8D'Cunha J. Herndon 2nd, J.E. Herzan D.L. et al.Poor correspondence between clinical and pathologic staging in stage 1 non-small cell lung cancer: results from Cancer and Leukemia Group B 9761, a prospective trial.Lung Cancer. 2005; 48: 241-246Abstract Full Text Full Text PDF PubMed Scopus (84) Google Scholar]. Therefore, because decisions regarding cancer treatment are based on tumor staging, an accurate MLN evaluation must include a histologic assessment of LN tissue.MediastinoscopyCervical mediastinoscopy is the gold standard for screening of NSCLC MLN metastasis [9Coughlin M. Deslauriers J. Beaulieu M. et al.Role of mediastinoscopy in pretreatment staging of patients with primary lung cancer.Ann Thorac Surg. 1985; 40: 556-560Abstract Full Text PDF PubMed Scopus (174) Google Scholar, 10Cybulsky I.J. Bennett W.F. Mediastinoscopy as a routine outpatient procedure.Ann Thorac Surg. 1994; 58: 176-178Abstract Full Text PDF PubMed Scopus (92) Google Scholar, 11Hammoud Z.T. Anderson R.C. Meyers B.F. et al.The current role of mediastinoscopy in the evaluation of thoracic disease.J Thorac Cardiovasc Surg. 1999; 118: 894-899Abstract Full Text Full Text PDF PubMed Scopus (263) Google Scholar, 12Luke W.P. Pearson F.G. Todd T.R. Patterson G.A. Cooper J.D. Prospective evaluation of mediastinoscopy for assessment of carcinoma of the lung.J Thorac Cardiovasc Surg. 1986; 91: 53-56PubMed Google Scholar, 13Patterson G.A. Ginsberg R.J. Poon P.Y. et al.A prospective evaluation of magnetic resonance imaging, computed tomography, and mediastinoscopy in the preoperative assessment of mediastinal node status in bronchogenic carcinoma.J Thorac Cardiovasc Surg. 1987; 94: 679-684PubMed Google Scholar]. During standard mediastinoscopy, stations 2L, 2R, 4L, 4R, and 7 are sampled for histologic assessment. In general, the majority of NSCLC patients, even those with negative imaging studies, should undergo mediastinoscopy before definitive decisions regarding therapy are made. In experienced hands, mediastinoscopy is safe, even after neoadjuvant radiation therapy [14Pauwels M. Van Schil P. De Backer W. Van den Brande F. Eyskens E. Repeat mediastinoscopy in the staging of lung cancer.Eur J Cardiothorac Surg. 1998; 14: 271-273Crossref PubMed Scopus (45) Google Scholar]. Three large series (each involving over 1,000 patients) have demonstrated very low morbidity rates (0.2% to 1.3%) and mortality rates (0% to 0.2%) after mediastinoscopy [9Coughlin M. Deslauriers J. Beaulieu M. et al.Role of mediastinoscopy in pretreatment staging of patients with primary lung cancer.Ann Thorac Surg. 1985; 40: 556-560Abstract Full Text PDF PubMed Scopus (174) Google Scholar, 10Cybulsky I.J. Bennett W.F. Mediastinoscopy as a routine outpatient procedure.Ann Thorac Surg. 1994; 58: 176-178Abstract Full Text PDF PubMed Scopus (92) Google Scholar, 11Hammoud Z.T. Anderson R.C. Meyers B.F. et al.The current role of mediastinoscopy in the evaluation of thoracic disease.J Thorac Cardiovasc Surg. 1999; 118: 894-899Abstract Full Text Full Text PDF PubMed Scopus (263) Google Scholar] with excellent results (Table 1). Left upper lobe tumors have a predilection to metastasize to LN stations 5 and 6, which are not accessible by standard mediastinoscopy. An extended cervical mediastinoscopy allows access to these LN stations. It obviates the need for a second incision (ie, anterior parasternal mediastinotomy [Chamberlain procedure]), it is safe, and it facilitates more accurate nodal staging [15Ginsberg R.J. Rice T.W. Goldberg M. Waters P.F. Schmocker B.J. Extended cervical mediastinoscopy A single staging procedure for bronchogenic carcinoma of the left upper lobe.J Thorac Cardiovasc Surg. 1987; 94: 673-678PubMed Google Scholar].Table 1Screening Techniques for Mediastinal Lymph Node StagingaSee reference 50;Sensitivity (%)Specificity (%)Negative Predictive Value (%)Positive Predictive Value (%)Accuracy (%)Transbronchial FNA8554–89EUS-FNA7697919291EBUS-FNA58–84Mediastinoscopy66–9310088–9310090–95.2Chamberlain691008910091Sentinel MLNSbWhen a sentinel MLN was able to be identified. Blue dye alone63–7580–9227 With radiocolloid74–901008947–90TEMLA901009510096EBUS = endobronchial ultrasound; EUS = endoscopic ultrasound; FNA = fine-needle aspiration; MLN = mediastinal lymph node; MLNS = mediastinal lymph node sampling; TEMLA = transcervical extended mediastinal lymphadenectomy.a See reference 50Ludwig M.S. Goodman M. Miller D.L. Johnstone P.A. Postoperative survival and the number of lymph nodes sampled during resection of node-negative non-small cell lung cancer.Chest. 2005; 128: 1545-1550Crossref PubMed Scopus (218) Google Scholar;b When a sentinel MLN was able to be identified. Open table in a new tab Emerging TechniquesA limitation of mediastinoscopy is its inability to access a number of MLN stations. A number of techniques, such as transcervical extended mediastinal lymphadenectomy [16Kuzdzal J. Zielinski M. Papla B. et al.Transcervical extended mediastinal lymphadenectomy—the new operative technique and early results in lung cancer staging.Eur J Cardiothorac Surg. 2005; 27: 384-390Crossref PubMed Scopus (106) Google Scholar, 17Kuzdzal J. Zielinski M. Papla B. et al.The transcervical extended mediastinal lymphadenectomy versus cervical mediastinoscopy in non-small cell lung cancer staging.Eur J Cardiothorac Surg. 2007; 31: 88-94Crossref PubMed Scopus (60) Google Scholar], sentinel MLNS [18Liptay M.J. Grondin S.C. Fry W.A. et al.Intraoperative sentinel lymph node mapping in non-small-cell lung cancer improves detection of micrometastases.J Clin Oncol. 2002; 20: 1984-1988Crossref PubMed Scopus (94) Google Scholar, 19Little A.G. DeHoyos A. Kirgan D.M. Arcomano T.R. Murray K.D. Intraoperative lymphatic mapping for non-small cell lung cancer: the sentinel node technique.J Thorac Cardiovasc Surg. 1999; 117: 220-224Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar, 20Rzyman W. Hagen O.M. Dziadziuszko R. et al.Intraoperative, radio-guided sentinel lymph node mapping in 110 nonsmall cell lung cancer patients.Ann Thorac Surg. 2006; 82: 237-242Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar, 21Rzyman W. Hagen O.M. Dziadziuszko R. et al.Blue-dye intraoperative sentinel lymph node mapping in early non-small cell lung cancer.Eur J Surg Oncol. 2006; 32: 462-465Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar, 22Sugi K. Kaneda Y. Sudoh M. Sakano H. Hamano K. Effect of radioisotope sentinel node mapping in patients with cT1 N0 M0 lung cancer.J Thorac Cardiovasc Surg. 2003; 126: 568-573Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar], conventional transbronchial fine-needle aspiration [23Schenk D.A. Chambers S.L. Derdak S. et al.Comparison of the Wang 19-gauge and 22-gauge needles in the mediastinal staging of lung cancer.Am Rev Respir Dis. 1993; 147: 1251-1258Crossref PubMed Scopus (156) Google Scholar], endobronchial ultrasound-guided fine-needle aspiration [24Herth F. Becker H.D. Ernst A. Conventional vs endobronchial ultrasound-guided transbronchial needle aspiration: a randomized trial.Chest. 2004; 125: 322-325Crossref PubMed Scopus (363) Google Scholar], and endoscopic ultrasound-guided fine-needle aspiration [25Annema J.T. Versteegh M.I. Veselic M. et al.Endoscopic ultrasound added to mediastinoscopy for preoperative staging of patients with lung cancer.JAMA. 2005; 294: 931-936Crossref PubMed Scopus (170) Google Scholar], are emerging as potential alternatives or adjuncts to mediastinoscopy. Each of these emerging techniques needs further evaluation, but the efficacy of some of these techniques approaches that of mediastinoscopy (Table 1). A potential advantage of these technologies over mediastinoscopy is the ability to evaluate LN stations not accessible by standard mediastinoscopy (ie, LN stations 10 and 11).LN Management at the Time of Definitive ResectionDue to potential false-negative results with computed tomography and positron emission tomography (ie, either alone, in combination, or as a fusion study) and with mediastinoscopy (or other histologic screening techniques), a significant number of patients who are staged by these techniques alone would be under staged and would therefore receive suboptimal therapy. Consequently, definitive MLN staging during primary tumor resection is essential; there are three options: (1) no defined evaluation, (2) MLNS, and (3) MLND.Improved accuracy of MLN evaluation could potentially influence survival through two mechanisms: (1) due to a direct therapeutic effect from resection of unsuspected N2 disease or (2) due to stage migration (also known as the "Will Rogers phenomenon") [26Feinstein A.R. Sosin D.M. Wells C.K. The Will Rogers phenomenon Stage migration and new diagnostic techniques as a source of misleading statistics for survival in cancer.N Engl J Med. 1985; 312: 1604-1608Crossref PubMed Scopus (1276) Google Scholar]. Evidence of an unbiased survival advantage from removing occult N2 disease is difficult to obtain and interpret. The best data to evaluate this mechanism would come from pathologic stage-matched groups of patients where MLN techniques were compared; however the potential for stage migration is still present. In stage migration, NSCLC patients who would have been erroneously understaged by imprecise modalities (ie, no defined evaluation or MLNS) are correctly staged by more accurate techniques (ie, MLND); these patients "migrate" toward their true (higher) stage. Because stage is directly associated with prognosis, the perceived survival benefit of MLND may be a taxonomic artifact because MLND is associated with a lower probability of stage misclassification, and the survival analysis by TNM stage is less likely to be biased by the diluting effects of understaged patients. Although the true effect may be attributable to contributions from both mechanisms, it is nevertheless important to adequately and accurately evaluate the MLN.MLND Versus MLNS TechniqueSeveral cohort studies and randomized trials provided evidence for and against the theoretical disadvantages of MLND compared with MLNS. In the subsequent review, the definitions of MLND and MLNS were based on the definition of these procedures used in the original studies. No defined evaluation was defined as either haphazard or no LN evaluation.In the literature, definitions of MLND and MLNS have been variable with some overlap between one author's MLNS being another's MLND; many definitions were vague and the detail of the nodes sampled inconsistent. The most clearly defined and thorough definition of MLNS and MLND was used by The American College of Surgeons Oncology Group Z0030 trial, a prospective trial of 1,023 patients undergoing NSCLC resection with either MLNS or MLND, with evaluation of perioperative morbidity and long-term survival. In this trial, MLNS was defined as sampling LNs from stations 2R, 4R, 7, and 10R for right-sided tumors and from stations 5, 6, 7, and 10L for left-sided tumors. The definition of MLND used was removal of all lymphatic tissue bounded by the right upper lobe bronchus, the innominate artery, the superior vena cava, and the trachea for right-sided tumors, and by the phrenic nerve, vagus nerve, top of the aortic arch, and the left mainstem bronchus for left-sided tumors; all lymphatic tissue at stations 7, 8, 9, 11, and 12 were removed regardless of the side of the tumor [27Allen M.S. Darling G.E. Pechet T.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 (discussion 1019–20): 1013-1019Abstract Full Text Full Text PDF PubMed Scopus (549) Google Scholar].MLND Versus MLNS and MorbidityBecause MLND is more extensive, a theoretic disadvantage is an associated higher morbidity rate. Okada and colleagues [28Okada M. Sakamoto T. Yuki T. Mimura T. Miyoshi K. Tsubota N. Selective mediastinal lymphadenectomy for clinico-surgical stage I non-small cell lung cancer.Ann Thorac Surg. 2006; 81: 1028-1032Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar] compared the morbidity rates of a prospective cohort of 377 patients who underwent MLNS with 358 patients in a historical control group who underwent MLND, and they demonstrated a significantly higher morbidity rate in the MLND control group. In the Okada and colleagues [28Okada M. Sakamoto T. Yuki T. Mimura T. Miyoshi K. Tsubota N. Selective mediastinal lymphadenectomy for clinico-surgical stage I non-small cell lung cancer.Ann Thorac Surg. 2006; 81: 1028-1032Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar] study, MLNS had an overall complication rate of 10.1% versus 17.3% for the MLND control. Although not statistically described individually, the MLND control group had higher raw numbers of dysrhythmia, pneumonia and atelectasis, chylothorax, and persistent air leak [28Okada M. Sakamoto T. Yuki T. Mimura T. Miyoshi K. Tsubota N. Selective mediastinal lymphadenectomy for clinico-surgical stage I non-small cell lung cancer.Ann Thorac Surg. 2006; 81: 1028-1032Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar]. Several other observational studies failed to show a difference in mortality [29Doddoli C. Aragon A. Barlesi F. et al.Does the extent of lymph node dissection influence outcome in patients with stage I non-small-cell lung cancer?.Eur J Cardiothorac Surg. 2005; 27: 680-685Crossref PubMed Scopus (135) Google Scholar, 30Lardinois D. Suter H. Hakki H. Rousson V. Betticher D. Ris H.B. Morbidity, survival, and site of recurrence after mediastinal lymph-node dissection versus systematic sampling after complete resection for non-small cell lung cancer.Ann Thorac Surg. 2005; 80: 268-274Abstract Full Text Full Text PDF PubMed Scopus (156) Google Scholar]. Furthermore, the American College of Surgeons Oncology Group Z0030 trial provided level I evidence that the morbidity rate after MLND and MLNS does not significantly differ. No significant difference was identified between MLND and MLNS for any of the 15 complications measured. In the American College of Surgeons Oncology Group Z0030, the MLND group had a greater median operative time than did the MLNS group by 15 minutes (p < 0.0001) [27Allen M.S. Darling G.E. Pechet T.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 (discussion 1019–20): 1013-1019Abstract Full Text Full Text PDF PubMed Scopus (549) Google Scholar]. Another theoretic disadvantage of MLND is a higher mortality rate as compared with MLNS. However, multiple observational studies [28Okada M. Sakamoto T. Yuki T. Mimura T. Miyoshi K. Tsubota N. Selective mediastinal lymphadenectomy for clinico-surgical stage I non-small cell lung cancer.Ann Thorac Surg. 2006; 81: 1028-1032Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar, 31Gajra A. Newman N. Gamble G.P. Kohman L.J. Graziano S.L. Effect of number of lymph nodes sampled on outcome in patients with stage I non-small-cell lung cancer.J Clin Oncol. 2003; 21: 1029-1034Crossref PubMed Scopus (256) Google Scholar] and prospective randomized clinical trials revealed no significant difference in the mortality rate between MLND and MLNS.Mediastinal LN dissection is a slightly longer procedure than MLNS (ie, between 15 [27Allen M.S. Darling G.E. Pechet T.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 (discussion 1019–20): 1013-1019Abstract Full Text Full Text PDF PubMed Scopus (549) Google Scholar, 32Oda M. Watanabe Y. Shimizu J. et al.Extent of mediastinal node metastasis in clinical stage I non-small-cell lung cancer: the role of systematic nodal dissection.Lung Cancer. 1998; 22: 23-30Abstract Full Text Full Text PDF PubMed Scopus (92) Google Scholar] and 30 minutes [27Allen M.S. Darling G.E. Pechet T.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 (discussion 1019–20): 1013-1019Abstract Full Text Full Text PDF PubMed Scopus (549) Google Scholar]). However, we believe that the higher survival rates after MLND, and its equivalent perioperative morbidity and mortality rates (as compared with MLNS), make MLND the most appropriate method for definitively staging MLNs.Survival and Extent of Nodal EvaluationMultiple cohort and randomized trials demonstrated evidence for one theoretical advantage of MLND (ie, higher patient survival rates, possibly due to more effective local tumor control resulting from a more complete MLN dissection). Whereas data for the American College of Surgeons Oncology Group Z0030 trial mature, with survival data that will likely become available within the next 5 years, one is able to discern credible information on the survival of patients who undergo MLND or MLNS from the smaller randomized trials and cohort studies available in the literature.Due to a potential for false-negative results with staging prior to definitive resection, no defined evaluation is inappropriate because a significant number of patients would be understaged and therefore would undergo suboptimal therapy. In a retrospective cohort study involving 442 patients with clinical stage I NSCLC, those who underwent random sampling had a significantly lower survival rate (51% vs 80%; p < 0.001) than those who underwent MLNS (defined as removal of at least 1 LN from stations 4, 7, and 10 for right-sided tumors and at least 1 LN from stations 5, 6, and 10 for left-sided tumors) or MLND (defined as "the prevailing surgical standard") [30Lardinois D. Suter H. Hakki H. Rousson V. Betticher D. Ris H.B. Morbidity, survival, and site of recurrence after mediastinal lymph-node dissection versus systematic sampling after complete resection for non-small cell lung cancer.Ann Thorac Surg. 2005; 80: 268-274Abstract Full Text Full Text PDF PubMed Scopus (156) Google Scholar]. These data are most likely an example of stage migration. Therefore, no defined evaluation is unacceptable.The results of several studies imply that MLND is not required for small tumors [31Gajra A. Newman N. Gamble G.P. Kohman L.J. Graziano S.L. Effect of number of lymph nodes sampled on outcome in patients with stage I non-small-cell lung cancer.J Clin Oncol. 2003; 21: 1029-1034Crossref PubMed Scopus (256) Google Scholar]. Oda and colleagues [33Sugi K. Nawata K. Fujita N. 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 (discussion 294–5): 290-294Crossref PubMed Scopus (191) Google Scholar] proposed that the size of the primary tumor and its histopathologic characteristics should drive the need for MLND. From their retrospective review of 524 patients, Oda and colleagues [33Sugi K. Nawata K. Fujita N. 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 (discussion 294–5): 290-294Crossref PubMed Scopus (191) Google Scholar] advocated not performing MLND for patients with clinical stage I NSCLC who have one or more of the following conditions: an adenocarinoma less than 10 mm, a peripheral squamous cell carcinoma less than 20 mm, or a central squamous cell carcinoma less than 30 mm [34Keller S.M. Adak S. Wagner H. Johnson D.H. 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 (discussion 365–6): 358-365Abstract Full Text Full Text PDF PubMed Scopus (310) Google Scholar]. Their results have not been validated and until future prospective randomized trials provide evidence to the contrary, MLND should be considered the standard of care.The differences in survival rates between MLND and MLNS may be due to enhanced MLN staging with MLND (ie, stage migration). Doddoli and colleagues [35Keller S.M. Adak S. Wagner H. et al.A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIA non-small-cell lung cancer Eastern Cooperative Oncology Group.N Engl J Med. 2000; 343: 1217-1222Crossref PubMed Scopus (446) Google Scholar] demonstrated that statistically there were significantly more MLNs collected during MLND (mean, 18.6 vs 7 LN; p = 0.001) and more stations were harvested (mean, 2.7 vs 1 LN; p < 0.001). These differences may account for the improved sensitivity of MLND (vs MLNS) in staging MLNs, which in turn leads to more accurate staging and more appropriate choices of cancer treatment. Indeed, large retrospective analyses have demonstrated that an increased number of nodes sampled leads to improved accuracy in pathologic staging [29Doddoli C. Aragon A. Barlesi F. et al.Does the extent of lymph node dissection influence outcome in patients with stage I non-small-cell lung cancer?.Eur J Cardiothorac Surg. 2005; 27: 680-685Crossref PubMed Scopus (135) Google Scholar] and, in turn, to increased survival rates [29Doddoli C. Aragon A. Barlesi F. et al.Does the extent of lymph node dissection influence outcome in patients with stage I non-small-cell lung cancer?.Eur J Cardiothorac Surg. 2005; 27: 680-685Crossref PubMed Scopus (135) Google Scholar, 31Gajra A. Newman N. Gamble G.P. Kohman L.J. Graziano S.L. Effect of number of lymph nodes sampled on outcome in patients with stage I non-small-cell lung cancer.J Clin Oncol. 2003; 21: 1029-1034Crossref PubMed Scopus (256) Google Scholar, 35Keller S.M. Adak S. Wagner H. et al.A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIA non-small-cell lung cancer Eastern Cooperative Oncology Group.N Engl J Med. 2000; 343: 1217-1222Crossref PubMed Scopus (446) Google Scholar].Although the differences seen in the study by Doddoli and colleagues [29Doddoli C. Aragon A. Barlesi F. et al.Does the extent of lymph node dissection influence outcome in patients with stage I non-small-cell lung cancer?.Eur J Cardiothorac Surg. 2005; 27: 680-685Crossref PubMed Scopus (135) Google Scholar] could be attributed to stage migration, the same data could argue the point that the improved survival of the MLND group is a result of a direct therapeutic effect from resection of unsuspected N2 disease. Doddoli and colleagues [35Keller S.M. Adak S. Wagner H. et al.A randomized trial of postoperative adjuvant therapy in patients with completely resected stage II or IIIA non-small-cell lung cancer Eastern Cooperative Oncology Group.N Engl J Med. 2000; 343: 1217-1222Crossref PubMed Scopus (446) Google Scholar] performed a retrospective cohort study involving 465 patients with pathologic stage I NSCLC who underwent either MLND (defined as more than 10 nodes identified and 2 or more stations examined) or MLNS (defined as fewer than 10 nodes identified or 1 station examined); the choice of MLND or MLNS
Referência(s)