HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Bryan A. Whitson Michael A. Maddaus Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Whitson, B. A. Articles by Maddaus, M. A. Search for Related Content PubMed PubMed Citation Articles by Whitson, B. A. Articles by Maddaus, M. A. Related Collections Lung - cancer

Ann Thorac Surg 2007;84:1059-1065
© 2007 The Society of Thoracic Surgeons

---

Review

Surgical Assessment and Intraoperative Management of Mediastinal Lymph Nodes in Non-Small Cell Lung Cancer

University of Minnesota Department of Surgery, Section of Thoracic and Foregut Surgery, Minneapolis, Minnesota

^_* Address correspondence to Dr Maddaus, University of Minnesota Department of Surgery, MMC 207, 420 Delaware St SE, Minneapolis, MN 55455 (Email: madda001{at}umn.edu).

	Abstract

Top Abstract Introduction Methods Pathologic Staging of MLN:... Mediastinoscopy Emerging Techniques LN Management at the... Number of Nodes and... Recommendations Acknowledgments References

 
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.

	Introduction

Top Abstract Introduction Methods Pathologic Staging of MLN:... Mediastinoscopy Emerging Techniques LN Management at the... Number of Nodes and... Recommendations Acknowledgments References

 
A critical determinant of survival in non-small cell lung cancer (NSCLC) patients is nodal status at the time of tumor staging [1, 2]. 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 [3]. 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 [3]. 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%) [3].

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.

	Methods

Top Abstract Introduction Methods Pathologic Staging of MLN:... Mediastinoscopy Emerging Techniques LN Management at the... Number of Nodes and... Recommendations Acknowledgments References

 
We 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 [4].

	Pathologic Staging of MLN: Operative Approaches

Top Abstract Introduction Methods Pathologic Staging of MLN:... Mediastinoscopy Emerging Techniques LN Management at the... Number of Nodes and... Recommendations Acknowledgments References

 
Although positron emission tomography and computed tomographic fusion scans are the most sensitive and accurate radiographic means of screening for MLN metastasis [5–7], 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 [8]. Therefore, because decisions regarding cancer treatment are based on tumor staging, an accurate MLN evaluation must include a histologic assessment of LN tissue.

	Mediastinoscopy

Top Abstract Introduction Methods Pathologic Staging of MLN:... Mediastinoscopy Emerging Techniques LN Management at the... Number of Nodes and... Recommendations Acknowledgments References

 
Cervical mediastinoscopy is the gold standard for screening of NSCLC MLN metastasis [9–13]. 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 [14]. 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 [9–11] 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 [15].

	Emerging Techniques

Top Abstract Introduction Methods Pathologic Staging of MLN:... Mediastinoscopy Emerging Techniques LN Management at the... Number of Nodes and... Recommendations Acknowledgments References

	LN Management at the Time of Definitive Resection

Top Abstract Introduction Methods Pathologic Staging of MLN:... Mediastinoscopy Emerging Techniques LN Management at the... Number of Nodes and... Recommendations Acknowledgments References

 
Due 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") [26]. 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 Technique
Several 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 [27].

MLND Versus MLNS and Morbidity
Because MLND is more extensive, a theoretic disadvantage is an associated higher morbidity rate. Okada and colleagues [28] 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 [28] 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 [28]. Several other observational studies failed to show a difference in mortality [29, 30]. 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) [27]. Another theoretic disadvantage of MLND is a higher mortality rate as compared with MLNS. However, multiple observational studies [28, 31] 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 [27, 32] and 30 minutes [27]). 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 Evaluation
Multiple 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") [30]. 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 [31]. Oda and colleagues [33] 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 [33] 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 [34]. 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 [35] 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 [29] and, in turn, to increased survival rates [29, 31, 35].

Although the differences seen in the study by Doddoli and colleagues [29] 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 [35] 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 was made at the surgeon’s discretion. Multivariate analysis demonstrated that MLND was associated with a significantly higher overall 5-year survival rate (64.7%) than MLNS (59.1%) [31, 36].

The studies by Doddoli [29] and Gajra [31], although both show survival advantages for MLND over MLNS, could argue for a direct therapeutic effect of MLND. In the studies, the patients were pathologic stage I NSCLC rather than clinical stage. This pathologic classification after operation allows for following survival in stage-matched groups. In both, the MLND cohorts had improved survivals.

In a prospective cohort study involving 100 consecutive patients with clinical stage T_1-3N_0-1M₀ NSCLC without evidence of MLN metastasis after mediastinoscopy, survival rates were compared after MLNS (ie, removal of one or more LN from stations 2 to 4 and 7 to 9 for right-sided tumors and from stations 4 to 9 for left-sided tumors) versus MLND (ie, removal of all lymphatic tissue from stations 2 to 4 and 7 to 9 for right-sided tumors and from stations 4 to 9 for left-sided tumors). Overall, MLND did not confer lower local recurrence rates or lower patient survival rates. However, subgroup analyses demonstrated significantly lower local recurrence rates after MLND (vs MLNS) in patients with pathologic stage I disease (12.5% vs 45%; p = 0.002) and in patients with N0 or N1 disease (46% vs 13%; p = 0.004). Disease-free survival was significantly higher after MLND (vs MLNS) in patients with pathologic stage I disease (mean survival, 60.2 vs 44.8 months; p < 0.03) [31]. The failure to detect lower recurrence rates and higher patient survival rates in all subgroups after MLND may be due to small sample sizes (ie, lack of statistical power) or to the nonrandomized nature of the study design, which increases the probability of bias.

The Eastern Cooperative Oncology Group (ECOG) 3590, a prospective randomized trial involving 373 patients, was designed to determine whether or not combination chemotherapy and concurrent radiation therapy were superior to radiation therapy alone in preventing local recurrence and prolonging survival in patients with completely resected stage II and stage IIIa NSCLCs [30]. Because all patients who participated in this trial were required to undergo either MLNS (defined as complete removal of at least 1 LN from stations 4, 7, and 10 at right thoracotomy and from stations 5 or 6, or both, and station 7 during left thoracotomy) or MLND (defined as complete removal of all lymphatic tissue at those levels), a subgroup analysis was performed; the overall survival rates after MLND versus MLNS were compared. Mediastinal LN dissection was associated with more favorable overall survival rates. Patients with N1, N2, and right-sided tumors had higher overall survival rates after MLND. However, MLND (vs MNLS) did not confer a survival advantage to patients with left-sided tumors [37]. The Eastern Cooperative Oncology Group 3590 authors speculated that the lack of survival benefit for patients with left-sided disease may be due to difficulty accessing the paratracheal, perivascular, subcarinal, and paraesophageal MLNs [36]. There are several other potential sources of bias. Because Eastern Cooperative Oncology Group 3590 was not designed to compare survival of the MLND versus the MLNS, there is a potential for selection bias. In addition, probability of confounding is high; patients who underwent MLND statistically had a significantly higher rate of multilevel N2 disease that was associated with a worse prognosis. Therefore, the inability of Eastern Cooperative Oncology Group 3590 to detect a survival advantage with left-sided disease should be interpreted cautiously.

One prospective randomized trial provided level I evidence for higher survival rates after MLND. In that trial, 532 patients with resectable clinical stage I to IIIa NSCLC underwent either MLND or MLNS. Mediastinal LN dissection (vs MLNS) was statistically associated with a significantly higher survival rate in patients with stage I disease (82% vs 57%) or with stage IIIa disease (27% vs 6%). Patients with stage II disease had a marginally significant (p = 0.0523) survival advantage after MLND (vs MLNS) (ie, 32% vs 26.9%) [36].

Another prospective randomized trial failed to demonstrate a survival advantage after MLND. Izbicki and colleagues [32] randomized 182 patients who had no clinical evidence of N3 disease or metastasis to MLND (82 patients) or MLNS (100 patients). The two groups did not differ in terms of local recurrence rates or cancer-free survival rates [38]. However, the potential for bias is high. The MLND group in the Izbicki and colleagues [32] study had a significantly higher percentage of nonsquamous histology (77%) than the MLNS group (54%). Because nonsquamous histology has been shown to confer a worse prognosis than squamous cell carcinoma [32], the lack of a perceived survival benefit with MLND may be due to confounding. However, most concerning is that more than 10% of the patients were excluded from analysis after randomization because of positive margins or the finding of small cell lung cancer in the final pathologic diagnosis. Significantly more patients in the MLNS group were excluded (18 patients) than in the MLND group (1 patient). Because an intention-to-treat analysis was not used, there is a significant potential for bias. Therefore these results should be interpreted with caution.

There are many MLN locations to which a NSCLC primary tumor can metastasize, each of which has important prognostic implications. In particular, single-level N2 disease confers more favorable survival rates than multilevel N2 disease [39]. Mediastinal LN dissection is more accurate than MLNS at distinguishing single-level N2 disease from multilevel N2 disease [40–42]. Therefore the difference in survival conferred by MLND as with MLNS may be due, in part, to the superior ability of MLND to detect multilevel N2 disease. In fact, a prospective randomized clinical trial provides evidence in favor of this conjecture. In that trial, 373 NSCLC patients underwent either MLNS or MLND. The percentage of N1 and N2 nodes sampled between the two groups did not differ. However, MLND was able to identify multiple N2 levels in 30% of patients, and MLNS in only 12%. Patients who underwent MLND had a significantly higher survival rate (median survival, 57.5 months) than those who underwent MLNS (median survival, 29.2 months), presumably because patients who underwent MLND were more accurately staged and consequently were more likely to undergo optimal treatment of their cancer [36]. In addition to being more efficacious at detecting multilevel disease and contiguous N1N2 disease, MLND is also more effective than MLNS at identifying N2 skip metastasis (defined as N2 positive and N1 negative LN, resulting from noncontiguous LN metastasis) [36]. The 5-year survival rate for patients with skip metastasis is more favorable (34.4% to 41%) than patients with contiguous N1N2 disease (12.7 to 18.5%) [43]. Again, a thorough and accurate evaluation of the MLN can have implications on survival.

In the ACOSOC Z0030 trial, MLND identified 3.8% more patients with N2 disease than did MLNS [42, 44–46]. Presuming that randomization resulted in an equal distribution of patients with N2 among the MLNS and the MLND groups, MLNS missed 3.8% more patients with N2 disease than did MLND. Had N2 disease been accurately detected, those patients would have been upstaged, either from stage I to IIIa (in the case of previous N0 disease) or from stage II to IIIa (in the case of previous N1 disease). As a result, those patients would have undergone appropriate adjuvant therapy for the stage of their disease, potentially optimizing their chance of long-term survival. To detect those 3.8% of patients, 26 patients would need to undergo MLND to gain benefit from the more accurate diagnosis of N2 disease in 1 patient. Because 26 is a relatively low number needed to be treated, we believe that MLND is a more prudent choice than MLNS.

Video-Assisted Thoracoscopic Surgery MLND
Mediastinal LN dissection performed by video-assisted thoracoscopic surgery versus MLND performed through a thoracotomy are equally efficacious regarding the number of nodes that are harvested [47]. Furthermore, the operative mortality rates and the 5-year survival rates are not significantly different [48, 49]. However, video-assisted thoracoscopic surgery is associated with less morbidity. In particular, one series demonstrated that video-assisted thoracoscopic surgery patients had fewer chest tube days (mean, 5.8 days) than thoracotomy patients (mean, 7.6 days). Based on these results, current National Comprehensive Cancer Network practice guidelines state that video-assisted thoracoscopic surgery is an acceptable alternative approach while performing MLND, as long as oncologic principles are not compromised [48, 49].

	Number of Nodes and Survival

Top Abstract Introduction Methods Pathologic Staging of MLN:... Mediastinoscopy Emerging Techniques LN Management at the... Number of Nodes and... Recommendations Acknowledgments References

 
Accurate tumor-node-metastasis staging has important prognostic [50] and therapeutic implications [1, 41, 51–53]. Therefore, scrupulous MLN assessment should be undertaken for all NSCLC patients. A number of factors must be considered in determining the adequacy of a MLN evaluation, including a thorough pathologic assessment, the number of LNs removed and the number of LN stations assessed.

Mediastinal LN dissection is the gold standard for pathologic staging of MLNs. Importantly, the number of MLNs that are harvested is crucial; it directly affects the accuracy of pathologic staging [54] and is associated with improved disease-free and overall survival rates [29, 31, 52]. Although it is well-established that removing a sufficient number of LNs is necessary to accurately stage NSCLC patients, the optimal number of LNs that should be evaluated is contentious [31, 52].

In a review of the surveillance, epidemiology, and end-results database, the mortality rates of 16,800 patients with pathologic stage I disease (94% of whom did not undergo adjuvant radiation) was correlated with the number of MLNs evaluated at the time of surgical resection of the primary tumor. Patients who had 11 to 12 MLNs evaluated had the highest survival rate (median survival, 97 months), which was significantly higher than for patients who had 1 or 2 LN examined (median survival, 65 months). Patients were also further stratified into groups based on the number of MLNs examined (1 to 4, 5 to 8, 9 to 12, 13 to 16, and more than 16; 1 to 4 served as the reference group). A multivariate analysis was performed to control for potential confounding factors of survival. Patients were further stratified according to whether or not they underwent radiation therapy. As compared with the reference group, increases in survival were noted with increasing numbers of MLNs examined in patients who did not undergo radiation therapy; this result was possibly due to a reduction in sampling error. The highest survival rate was noted in the 13 to 16 MLN group. Evaluating more than 16 LNs did not confer an improvement in survival. Similar results were noted among patients who underwent adjuvant radiation therapy. The surveillance, epidemiology, and end-results review concluded that an adequate MLN evaluation involves the assessment of 11 to 16 LNs [29, 35, 52].

In addition to the overall number of MLNs examined, the number of stations is also crucial. The retrospective cohort study by Doddoli and colleagues [35] demonstrated that MLND provides a survival advantage in comparison with MLNS. Because the mean number of stations examined during MLND in that study was 2.7, they concluded that at least 2 MLN stations should be evaluated to provide accurate MLN staging [52].

In a subgroup analysis of a retrospective cohort study by Gajra and colleagues [31], patients who had three or more stations examined had statistically significantly higher survival rates as compared with patients who had two or fewer stations examined [29]. Based on the results of these studies, the current National Comprehensive Cancer Network practice guidelines recommend evaluating at least three N2 stations [31].

	Recommendations

Top Abstract Introduction Methods Pathologic Staging of MLN:... Mediastinoscopy Emerging Techniques LN Management at the... Number of Nodes and... Recommendations Acknowledgments References

 
To optimize the care and outcomes of NSCLC patients, educational programs are needed to distribute evidence-based practice guidelines to both community and academic physicians. From the literature we are able to make the following evidence-based recommendations:

• Mediastinoscopy should be performed in all patients considered potential candidates for definitive chemoradiation therapy or surgical resection. Decisions should not be based on clinical staging by imaging alone.

• Mediastinal LN dissection should be performed for all NCSLC patients.

• Video-assisted thoracoscopic surgery MLND is a safe, equally effective, and acceptable alternative to conventional MLND.

• At least 10 MLNs from three or more MLN stations should be examined.

	Acknowledgments

Top Abstract Introduction Methods Pathologic Staging of MLN:... Mediastinoscopy Emerging Techniques LN Management at the... Number of Nodes and... Recommendations Acknowledgments References

 
The authors would like to acknowledge Mary Knatterud, PhD, for her editorial assistance with this manuscript.

	References

Top Abstract Introduction Methods Pathologic Staging of MLN:... Mediastinoscopy Emerging Techniques LN Management at the... Number of Nodes and... Recommendations Acknowledgments References

 

1. Mountain CF. Revisions in the International System for Staging Lung Cancer Chest 1997;111:1710-1717.[Medline]
2. Naruke 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;96:440-447.[Abstract]
3. Little AG, Rusch VW, Bonner JA, et al. Patterns of surgical care of lung cancer patients Ann Thorac Surg 2005;80:2051-2056.[Abstract/Free Full Text]
4. Mountain CF, Dresler CM. Regional lymph node classification for lung cancer staging Chest 1997;111:1718-1723.[Medline]
5. Cerfolio RJ, Ojha B, Bryant AS, Raghuveer V, Mountz JM, Bartoluci AA. 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;78:1017-1023.[Abstract/Free Full Text]
6. Halpern BS, Schiepers C, Weber WA, et al. Presurgical staging of non-small cell lung cancer: positron emission tomography, integrated positron emission tomography/CT, and software image fusion Chest 2005;128:2289-2297.[Medline]
7. Magnani 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;40:741-748.[Medline]
8. D’Cunha J, Herndon 2nd JE, Herzan DL, 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;48:241-246.[Medline]
9. Coughlin M, Deslauriers J, Beaulieu M, et al. Role of mediastinoscopy in pretreatment staging of patients with primary lung cancer Ann Thorac Surg 1985;40:556-560.[Abstract]
10. Cybulsky IJ, Bennett WF. Mediastinoscopy as a routine outpatient procedure Ann Thorac Surg 1994;58:176-178.[Abstract]
11. Hammoud ZT, Anderson RC, Meyers BF, et al. The current role of mediastinoscopy in the evaluation of thoracic disease J Thorac Cardiovasc Surg 1999;118:894-899.[Abstract/Free Full Text]
12. Luke WP, Pearson FG, Todd TR, Patterson GA, Cooper JD. Prospective evaluation of mediastinoscopy for assessment of carcinoma of the lung J Thorac Cardiovasc Surg 1986;91:53-56.[Abstract]
13. Patterson GA, Ginsberg RJ, Poon PY, 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;94:679-684.[Abstract]
14. Pauwels 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;14:271-273.[Medline]
15. Ginsberg RJ, Rice TW, Goldberg M, Waters PF, Schmocker BJ. Extended cervical mediastinoscopyA single staging procedure for bronchogenic carcinoma of the left upper lobe. J Thorac Cardiovasc Surg 1987;94:673-678.[Abstract]
16. Kuzdzal 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;27:384-390.[Abstract/Free Full Text]
17. Kuzdzal 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;31:88-94.[Abstract/Free Full Text]
18. Liptay MJ, Grondin SC, Fry WA, et al. Intraoperative sentinel lymph node mapping in non-small-cell lung cancer improves detection of micrometastases J Clin Oncol 2002;20:1984-1988.[Abstract/Free Full Text]
19. Little AG, DeHoyos A, Kirgan DM, Arcomano TR, Murray KD. Intraoperative lymphatic mapping for non-small cell lung cancer: the sentinel node technique J Thorac Cardiovasc Surg 1999;117:220-224.[Abstract/Free Full Text]
20. Rzyman W, Hagen OM, Dziadziuszko R, et al. Intraoperative, radio-guided sentinel lymph node mapping in 110 nonsmall cell lung cancer patients Ann Thorac Surg 2006;82:237-242.[Abstract/Free Full Text]
21. Rzyman W, Hagen OM, Dziadziuszko R, et al. Blue-dye intraoperative sentinel lymph node mapping in early non-small cell lung cancer Eur J Surg Oncol 2006;32:462-465.[Medline]
22. Sugi 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;126:568-573.[Abstract/Free Full Text]
23. Schenk DA, Chambers SL, 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;147:1251-1258.[Medline]
24. Herth F, Becker HD, Ernst A. Conventional vs endobronchial ultrasound-guided transbronchial needle aspiration: a randomized trial Chest 2004;125:322-325.[Medline]
25. Annema JT, Versteegh MI, Veselic M, et al. Endoscopic ultrasound added to mediastinoscopy for preoperative staging of patients with lung cancer JAMA 2005;294:931-936.[Abstract/Free Full Text]
26. Feinstein AR, Sosin DM, Wells CK. The Will Rogers phenomenonStage migration and new diagnostic techniques as a source of misleading statistics for survival in cancer. N Engl J Med 1985;312:1604-1608.[Abstract]
27. Allen MS, Darling GE, Pechet TT, 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;81:1013-1019discussion 1019–20.[Abstract/Free Full Text]
28. Okada 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;81:1028-1032.[Abstract/Free Full Text]
29. Doddoli 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;27:680-685.[Abstract/Free Full Text]
30. Lardinois D, Suter H, Hakki H, Rousson V, Betticher D, Ris HB. 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;80:268-274.[Abstract/Free Full Text]
31. 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;21:1029-1034.[Abstract/Free Full Text]
32. Oda 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;22:23-30.[Medline]
33. Sugi 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;22:290-294discussion 294–5.[Medline]
34. 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 cancerEastern Cooperative Oncology Group. Ann Thorac Surg 2000;70:358-365discussion 365–6.[Abstract/Free Full Text]
35. Keller SM, 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 cancerEastern Cooperative Oncology Group. N Engl J Med 2000;343:1217-1222.[Abstract/Free Full Text]
36. 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;36:1-6.[Medline]
37. 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;81:229-235.[Medline]
38. Ichinose Y, Yano T, Asoh H, Yokoyama H, Yoshino I, Katsuda Y. Prognostic factors obtained by a pathologic examination in completely resected non-small-cell lung cancerAn analysis in each pathologic stage. J Thorac Cardiovasc Surg 1995;110:601-605.[Abstract/Free Full Text]
39. Asamura H, Nakayama H, Kondo H, Tsuchiya R, Naruke T. Lobe-specific extent of systematic lymph node dissection for non-small cell lung carcinomas according to a retrospective study of metastasis and prognosis J Thorac Cardiovasc Surg 1999;117:1102-1111.[Abstract/Free Full Text]
40. Casali C, Stefani A, Natali P, Rossi G, Morandi U. Prognostic factors in surgically resected N2 non-small cell lung cancer: the importance of patterns of mediastinal lymph nodes metastases Eur J Cardiothorac Surg 2005;28:33-38.[Abstract/Free Full Text]
41. 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;79:225-233.[Abstract/Free Full Text]
42. Misthos P, Sepsas E, Athanassiadi K, Kakaris S, Skottis I. Skip metastases: analysis of their clinical significance and prognosis in the IIIA stage of non-small cell lung cancer Eur J Cardiothorac Surg 2004;25:502-508.[Abstract/Free Full Text]
43. Keller SM, Vangel MG, Wagner H, et al. Prolonged survival in patients with resected non-small cell lung cancer and single-level N2 disease J Thorac Cardiovasc Surg 2004;128:130-137.[Abstract/Free Full Text]
44. Prenzel KL, Monig SP, Sinning JM, et al. Role of skip metastasis to mediastinal lymph nodes in non-small cell lung cancer J Surg Oncol 2003;82:256-260.[Medline]
45. Yoshino I, Yokoyama H, Yano T, et al. Skip metastasis to the mediastinal lymph nodes in non-small cell lung cancer Ann Thorac Surg 1996;62:1021-1025.[Abstract/Free Full Text]
46. 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;27:745-752.[Abstract/Free Full Text]
47. Watanabe A, Koyanagi T, Ohsawa H, et al. Systematic node dissection by VATS is not inferior to that through an open thoracotomy: a comparative clinicopathologic retrospective study Surgery 2005;138:510-517.[Medline]
48. Ettinger DS, Bepler G, Bueno R, et al. Non-small cell lung cancer clinical practice guidelines in oncology J Natl Compr Canc Netw 2006;4:548-582.[Medline]
49. Henschke CI, Wisnivesky JP, Yankelevitz DF, Miettinen OS. Small stage I cancers of the lung: genuineness and curability Lung Cancer 2003;39:327-330.[Medline]
50. Ludwig MS, Goodman M, Miller DL, Johnstone PA. Postoperative survival and the number of lymph nodes sampled during resection of node-negative non-small cell lung cancer Chest 2005;128:1545-1550.[Medline]
51. Wisnivesky JP, Henschke C, McGinn T, Iannuzzi MC. Prognosis of Stage II non-small cell lung cancer according to tumor and nodal status at diagnosis Lung Cancer 2005;49:181-186.[Medline]
52. Ginsberg RJ. Resection of non-small cell lung cancer: how much and by what route Chest 1997;112:203S-205S.[Medline]
53. Sedrakyan A, Van Der Meulen J, O’Byrne K, Prendiville J, Hill J, Treasure T. Postoperative chemotherapy for non-small cell lung cancer: a systematic review and meta-analysis J Thorac Cardiovasc Surg 2004;128:414-419.[Abstract/Free Full Text]
54. Tubiana M. Radiotherapy in non-small cell lung cancerAn overview. Chest 1989;96:85S-87S.[Medline]

This article has been cited by other articles:

				B. A. Whitson, S. S. Groth, S. J. Duval, S. J. Swanson, and M. A. Maddaus 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., December 1, 2008; 86(6): 2008 - 2018. [Abstract] [Full Text] [PDF]

				S. S. Groth, B. A. Whitson, J. D'Cunha, M. A. Maddaus, M. Alsharif, and R. S. Andrade Endobronchial ultrasound-guided fine-needle aspiration of mediastinal lymph nodes: a single institution's early learning curve. Ann. Thorac. Surg., October 1, 2008; 86(4): 1104 - 1109. [Abstract] [Full Text] [PDF]

				S. D. Moffatt-Bruce, S. P. Povoski, S. Sharif, N. C. Hall, P. Ross Jr, M. A. Johnson, and E. W. Martin Jr A novel approach to positron emission tomography in lung cancer. Ann. Thorac. Surg., October 1, 2008; 86(4): 1355 - 1357. [Abstract] [Full Text] [PDF]

				W. Zhong, X. Yang, J. Bai, J. Yang, C. Manegold, and Y. Wu Complete mediastinal lymphadenectomy: the core component of the multidisciplinary therapy in resectable non-small cell lung cancer. Eur. J. Cardiothorac. Surg., July 1, 2008; 34(1): 187 - 195. [Abstract] [Full Text] [PDF]

				F. J. F. Herth, R. Eberhardt, M. Krasnik, and A. Ernst Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration of Lymph Nodes in the Radiologically and Positron Emission Tomography-Normal Mediastinum in Patients With Lung Cancer Chest, April 1, 2008; 133(4): 887 - 891. [Abstract] [Full Text] [PDF]

This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Bryan A. Whitson Michael A. Maddaus Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Whitson, B. A. Articles by Maddaus, M. A. Search for Related Content PubMed PubMed Citation Articles by Whitson, B. A. Articles by Maddaus, M. A. Related Collections Lung - cancer