Chest ACCP Education Calendar
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Guest Access | Sign In via User Name/Password
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Detterbeck, F. C.
Right arrow Articles by Silvestri, G. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Detterbeck, F. C.
Right arrow Articles by Silvestri, G. A.
(Chest. 2003;123:167S-175S.)
© 2003 American College of Chest Physicians

Invasive Staging*

The Guidelines

Frank C. Detterbeck, MD, FCCP; Malcolm M. DeCamp, Jr., MD, FCCP; Leslie J. Kohman, MD, FCCP and Gerard A. Silvestri, MD, FCCP

* From the Multidisciplinary Thoracic Oncology Program (Dr. Detterbeck), Division of Cardiothoracic Surgery, University of North Carolina, Chapel Hill, NC; Department of Thoracic and Cardiovascular Surgery (Dr. DeCamp), Cleveland Clinic Foundation, Cleveland, OH; Division of Cardiothoracic Surgery (Dr. Kohman), SUNY Health Science Center, Syracuse, NY; and Division of Pulmonary and Critical Care Medicine (Dr. Silvestri), Medical University of South Carolina, Charleston, SC.

Correspondence to: Frank C. Detterbeck, MD, Division of Cardiothoracic Surgery, Department of Surgery, University of North Carolina at Chapel Hill, CB #7065, 108 Burnett-Womack Building, Chapel Hill, NC 27599-7065; e-mail: fdetter{at}med.unc.edu


   Abstract
TOP
 Abstract
Introduction
 Techniques of Invasive...
 Clinical Questions
 Summary
 Summary of Recommendations
 References
 
A variety of invasive staging tests are available, including mediastinoscopy, thoracoscopy (video-assisted thoracoscopic surgery), transbronchial needle aspiration (TBNA), transthoracic needle aspiration (TTNA), and endoscopic ultrasound with fine needle aspiration (EUS-NA). Each of these tests requires specific skills, has particular risks, and has technical considerations making it more or less suitable for masses in particular locations. Therefore, direct comparisons among the tests are not possible, and the issue is to define which procedure is most useful for a particular situation. Invasive staging procedures are sometimes used to confirm the stage of a lung cancer, ie, when radiographic staging is not reliable. However, invasive staging procedures are also often used to confirm the diagnosis (ie, when the radiographic stage is reliable). The first situation requires a test with a low false-negative rate; the latter requires a test with high sensitivity. Clinicians must be clear about the question at hand and how to assess the value of a test when selecting an invasive staging procedure. When confirmation of the diagnosis is the primary issue, TBNA (or EUS-NA, if available) are good choices because of high sensitivity and low morbidity. When the primary issue is to confirm that there is no involvement of mediastinal lymph nodes, mediastinoscopy appears to be best suited to most situations. When the primary goal is to confirm malignant involvement of mediastinal nodes, mediastinoscopy also appears to be best in general, although TBNA, TTNA, and EUS-NA may be reasonable alternatives in certain situations. However, selection of a test will also depend on the local availability of expertise, and patient-specific anatomic and physiologic considerations. Selection of the optimal approach is best achieved through a multidisciplinary discussion so that all aspects can be weighed appropriately.

Key Words: anterior mediastinotomy • bronchoscopy • clinical staging • esophageal ultrasound • mediastinal lymph nodes • mediastinoscopy • pathologic staging • staging • transbronchial needle aspiration • transthoracic needle aspiration


   Introduction
TOP
 Abstract
 Introduction
Techniques of Invasive...
 Clinical Questions
 Summary
 Summary of Recommendations
 References
 
The workup of patients suspected to have a malignancy consists of several distinct steps (Table 1 ). The paradigm that a diagnosis must be obtained first, followed by appropriate staging and treatment, is simplistic and does not correspond to actual practice. In reality, the first step is an initial assessment based on the clinical presentation, risk factors, and radiographic appearance. This allows a presumptive diagnosis to be made as well as a presumptive stage. Sometimes, the presumptive diagnosis and stage can be made with sufficient reliability that a plan for treatment can be initiated (such as thoracotomy for a new spiculated parenchymal mass in a smoker with no enlarged nodes). However, usually confirmatory tests are necessary as the second step to prove or disprove the presumptive diagnosis and stage. It is the presumptive diagnosis and stage, however, that determines which confirmatory test is most appropriate. Accurate definition of the diagnosis and stage then allows the optimal treatment to be selected.


View this table:
[in this window]
[in a new window]

  		Table 1. Steps in the Workup of a Patient With Suspected Lung Cancer

 
This section deals with invasive staging procedures. Such procedures may be necessary to confirm the presumptive stage—for example, in instances where the clinical staging based on imaging studies alone is often inaccurate. Invasive staging procedures may also be done primarily to confirm the diagnosis—for example, in instances where the clinical stage by radiologic tests is considered to be accurate (ie, small cell lung cancer [SCLC]), but tissue confirmation of the cancer is necessary before treatment can be initiated. Because both of these questions are clinically important, invasive staging tests will be reviewed with regard to both of these questions (confirmation of stage vs confirmation of diagnosis). However, it is important not to use data that pertain to one of these questions out of context and apply it to patients in whom a different issue is to be addressed.

It is difficult to compare the results of one staging test to another. First, the clinical question being addressed by an invasive staging procedure varies. Second, the patient population for whom one clinical question is important is different from the group for whom another question is relevant. Finally, there are technical issues making certain procedures applicable only in specific situations. These considerations must be kept in mind when comparing various invasive staging procedures.

Various parameters can be used to assess the reliability of a test, including sensitivity, specificity, false-negative (FN), and false-positive (FP) rates. Sensitivity and specificity relate to theoretical patient populations, all of which either have or do not have the condition in question. Therefore, these parameters are defined after the fact by the true disease status. While there is some theoretical appeal to this approach, it makes it more difficult to apply prospectively to patients (in whom the true disease status is not known). These measures are most useful in choosing which confirmatory test to perform, because in theory these measures can be compared for different tests since they deal with the same theoretical population. However, in reality, comparison of the sensitivity and specificity of different invasive tests is sometimes difficult, because the patient populations selected for one test or another are not the same. Once a test has been performed, however, interpretation of the results is achieved by considering the FP and FN rates. These measures are not abstract because they are based on real populations of patients, who either have a positive or a negative test result. The FN and FP rates are sometimes expressed in a more obtuse manner as the percentage of 1 minus the FN (or FP) rate, known as the negative predictive value and positive predictive value.

It is important to be clear about the clinical context when discussing the stage of a patient. Five distinct contexts are recognized by the American Joint Committee on Cancer (Table 2 ). Ideally, we would like to have information about the presence or absence of tumor at a cellular level throughout the body in order to accurately know the true stage. In general, the pathologic stage is viewed as the closest approximation to the true stage. The pathologic stage is established by a surgical resection, including accurate assessment of potential areas of spread (such as lymph nodes), and careful examination of the tissues by a pathologist. While this may be the most accurate, it is not available until surgical treatment has been carried out. The clinical stage is that determined using all information available prior to any treatment, and thus is the most useful in actual practice. The information available may be limited (ie, involving only a chest CT) or extensive (ie, involving invasive procedures). It is important to note that an invasive staging procedure is still considered part of clinical staging, even though it may involve a surgical procedure (ie, mediastinoscopy) and evaluation by a pathologist.


View this table:
[in this window]
[in a new window]

  		Table 2. Clinical Staging Contexts

 

   Techniques of Invasive Mediastinal Staging
TOP
 Abstract
 Introduction
 Techniques of Invasive...
Clinical Questions
 Summary
 Summary of Recommendations
 References
 
A number of invasive tests are available to stage the mediastinum (Table 3 ). These include mediastinoscopy, the Chamberlain procedure (also known as an anterior mediastinotomy), transthoracic needle aspiration of mediastinum (TTNA), transbronchial needle aspiration (TBNA), esophageal endoscopic ultrasound with needle aspiration (EUS-NA), and video-assisted thoracic surgery (VATS), which is also known as thoracoscopy. Each of these is discussed individually first, followed by a discussion of which test to select for particular clinical questions.


View this table:
[in this window]
[in a new window]

  		Table 3. Techniques of Invasive Mediastinal Staging

 
Mediastinoscopy
Mediastinoscopy has long been the "gold standard" among staging tests of mediastinal lymph nodes. It is performed in the operating room, usually under general anesthesia, and in most US centers patients are usually discharged the same day if they are in stable condition after several hours of observation.1 2 3 The procedure involves an incision just above the suprasternal notch, insertion of a mediastinoscope alongside the trachea, and biopsy of mediastinal nodes. Rates of morbidity and mortality as a result of this procedure are low (2% and 0.08%, respectively).4 Left and right high and low paratracheal nodes (stations 2R, 2L, 4R, 4L), pretracheal nodes (stations 1, 3), and anterior subcarinal nodes (station 7) are accessible via this approach. Node groups that cannot be sampled with this technique include posterior subcarinal (station 7), inferior mediastinal (stations 8, 9), and aortopulmonary window and anterior mediastinal (stations 5, 6) nodes.

The average sensitivity of mediastinoscopy to detect mediastinal node involvement from cancer is approximately 80 to 85%, and the average FN rate is approximately 10% (see the chapter, "Invasive Staging for NSCLC: A Review of the Current Evidence," hereafter referred to as the background evidence chapter). Several authors have shown that approximately half (42 to 57%) of the FN cases were due to nodes that were not accessible by the mediastinoscope.5 6 7 8 9 The FN rate at mediastinoscopy is probably also affected by the diligence with which nodes are dissected and sampled at mediastinoscopy. Ideally, five nodal stations (stations 2R, 4R, 7, 4L, 2L) should routinely be examined, with at least one node sampled from each station unless none are present after actual dissection in the region of a particular node station. The specificity and the FP rates of mediastinoscopy are reported to be 100% and 0, respectively. Strictly speaking, these values cannot really be assessed because patients with a positive biopsy result were not subjected to any further procedures (such as thoracotomy) to confirm the results. Nevertheless, it seems reasonable to assume that the FP rate is low.

The patients included in these series have had potentially operable, nonmetastatic lung cancer with very few exceptions. The reported results provide data regarding the reliability of mediastinoscopy for staging of the mediastinal nodes as compared to thoracotomy in patients with lung cancer. Therefore, these results can be readily applied to potentially resectable patients to confirm invasively the stage of lung cancer.

Assessment of Aortopulmonary Window Lymph Nodes
Cancers in the left upper lobe (LUL) have a predilection for involvement of the nodes in the aortopulmonary window (APW) [station 5]. These nodes are classified as mediastinal nodes, and represent the most important group of N2 nodes that are not accessible by standard cervical mediastinoscopy. It has been suggested that nodes in this region should not be viewed as mediastinal nodes and that resection of patients should be performed regardless of APW node involvement, making assessment of these nodes superfluous.10 This was based on a selected subgroup of 23 completely resected patients who had APW node involvement as the only site of N2 disease. However, analysis of all of the data in this regard shows that survival of patients with only APW node involvement is not substantially different than that of patients with involvement of only a single N2 node station in another location.11 Therefore, the issue is more a matter of whether patients with involvement of a single mediastinal node station should undergo surgical resection, and not whether APW nodes should be classified as N2 nodes.

The classic way of invasively assessing this area is the Chamberlain procedure (also known as an anterior mediastinotomy), which involves an incision in the second or third intercostal space just to the left of the sternum. Traditionally, an overnight hospital stay was necessary, but in many institutions this is no longer found to be necessary, especially as surgeons have used visualization between the ribs more frequently as opposed to removal of a costal cartilage. The reliability of this procedure has not been extensively documented, despite its common use. The sensitivity of the Chamberlain procedure in addition to a standard cervical mediastinoscopy in patients with LUL tumors is approximately 87%, and the FN rate is approximately 10% (see background evidence chapter). Two additional studies regarding this procedure have not really addressed the reliability of the procedure for staging of non-small cell lung cancer (NSCLC). In one study, no actual biopsies were performed in most patients, and the procedure was used to assess resectability (resectable patients included those with bulky APW nodal involvement in this series).12 The other study used anterior mediastinotomy primarily for diagnosis (not staging), and included pulmonary biopsies and evaluation of patients with mediastinal masses.13 In fact, only a minority of patients included in this study had lung cancer.

Extended cervical mediastinoscopy offers an alternative way of invasive assessment of APW nodes, but is used in only a few institutions (see background evidence chapter). With this procedure, a mediastinoscope is inserted through the suprasternal notch and directed lateral to the aortic arch.14 In 100 consecutive patients with LUL cancers, standard mediastinoscopy and extended mediastinoscopy were found to have a sensitivity of 69% and an FN rate of 11% for detection of N2,3 disease (prevalence, 29%).14 Similar results (sensitivity, 81%; FN rate, 9%) were reported in another series of 93 such patients, all of whom had enlarged APW nodes.15 In approximately 550 patients undergoing extended cervical mediastinoscopy, two major complications (one stroke and one aortic injury) have been reported.14 15 16 17 18

Thoracoscopy has been used to assess some node stations not accessible by mediastinoscopy (stations 5, 6, 7, 8, 9). In 40 patients with enlarged APW or subazygous nodes who had a negative cervical mediastinoscopy results, thoracoscopy provided completely accurate staging in all, with no FN results.19

The patients included in these series of extended cervical mediastinoscopy or thoracoscopy have had potentially operable lung cancer with very few exceptions. The reported results provide data regarding the reliability of these tests for staging of mediastinal nodes as compared to thoracotomy in patients with lung cancer. Therefore, these results can be readily applied to potentially resectable patients to confirm invasively the stage of lung cancer.

EUS-NA also provides an alternative method of sampling APW nodes (see subsequent discussion). Data addressing the reliability of this procedure specifically for APW nodes in patients with LUL tumors is not available. In general, however, the sensitivity of this test is very high, although the FN rate is high enough to potentially be an issue.

Transthoracic Needle Aspiration
TTNA or biopsy for diagnosis and staging of the mediastinum is distinct from TTNA of parenchymal masses to achieve a diagnosis. The ability to carry out TTNA for diagnosis and staging of the mediastinum has generally been reported to be high (> 90%), although approximately 10% of patients require placement of a catheter for evacuation of a pneumothorax.20 The sensitivity has generally been reported to be approximately 90% (see background evidence chapter). However, the FN rate is 20 to 50%, indicating that a negative (noncancer) result cannot be relied on in a patient suspected of having cancer.

Patients selected for this procedure have generally had mediastinal lymph nodes > 1.5 cm. This is also evidenced by the fact that the prevalence of cancer in the mediastinal nodes was very high (> 80%). Furthermore, only approximately 75% of the patients had lung cancer (despite excluding studies in which only a minority of patients had lung cancer). Therefore, these results are most applicable to patients with bulky mediastinal involvement, in whom the purpose of the procedure was probably primarily to confirm the diagnosis and less likely to confirm the stage. Extrapolation of these results to patients with lesser amounts of mediastinal spread may be inappropriate.

Transbronchial Needle Aspiration
TBNA, also known as Wang needle aspiration, can be performed safely with no significant morbidity. It can be performed as an outpatient procedure, as with most bronchoscopic procedures. TBNA is used most frequently to assess subcarinal nodes. Paratracheal lymph nodes are sometimes more difficult to access, due to an inability to sufficiently angulate the bronchoscope and the needle. It is reported that it is feasible to get adequate specimens via TBNA in approximately 90% of cases.21 22 23 24 The sensitivity is approximately 75%, whereas the specificity is very high (see background evidence chapter). The sensitivity has been consistently reported to be high in series with a very high prevalence of N2,3 involvement, whereas it is low in series with a lower prevalence. The FN rate is approximately 30%, and occasional FP results have been reported in series in which this has been specifically examined with a confirmatory test.

The patients included in studies of TBNA have generally had a very high prevalence of N2,3 involvement, and the general implication is that the mediastinal nodes have been markedly enlarged, although few studies have reported specifics about node size. The results should not be applied to patients without extensive mediastinal involvement. In fact, the studies show that the sensitivity in these situations is much lower. Furthermore, the high FN rate makes this test less useful for staging of the mediastinum; its primary role is to provide a diagnosis in patients in whom there is already little doubt about mediastinal involvement based on the radiographic appearance alone.

Endoscopic Ultrasound and Needle Aspiration
EUS-NA of mediastinal lymph nodes through the wall of the esophagus has been performed with a negligible risk of infection or bleeding. Only one complication (transient fever) has been reported among five studies involving 288 patients.25 26 27 28 29 This technique is particularly useful for inferior pulmonary ligament, subcarinal, and APW nodes. Nodes that are anterolateral to the trachea (2R, 2L, 4R, 4L) are difficult to sample reliably (but are more commonly involved with lung cancer). There are no data regarding the feasibility of EUS-NA. The reported sensitivity is approximately 90% when a needle aspiration is performed. The FN rate of 23% is a potential drawback (see background evidence chapter). No data are available regarding specificity and FP rates from studies that involved an appropriate confirmatory test.

The patients included in these studies have been patients with NSCLC without evidence of distant metastases. However, most of the patients have had markedly enlarged lymph nodes, primarily in locations amenable to EUS-NA, although it is clear that nodes that are smaller than 1 cm can be sampled using this technique.26 29 Therefore, these results pertain primarily to patients with radiographic evidence of N2,3 involvement in whom the prevalence of such involvement is expected to be high. This procedure requires a skilled endoscopist with the necessary equipment, which is currently available in only a small number of institutions.

Video-Assisted Thoracic Surgery
Insufficient data are available to draw conclusions about the feasibility and reliability of VATS in assessing the mediastinum. In general, VATS is limited to an assessment of only one side of the mediastinum (unless a bilateral VATS is performed).

Other Staging Procedures
In patients with signs of advanced disease, clinical scenarios often occur that make other invasive procedures indicated, such as needle aspiration of a supraclavicular lymph node, thoracentesis or thoracoscopy of a pleural effusion, or needle aspiration or biopsy of a metastatic site such as an enlarged adrenal or hepatic mass. The indications for such procedures are covered in more detail in the chapters on diagnosis and noninvasive staging, and specific recommendation regarding such procedures can be found in these chapters as well. In brief, if an enlarged supraclavicular lymph node or a pleural effusion is present, it is generally prudent to pursue a diagnosis of these lesions. When the clinical presentation is entirely consistent with locally advanced disease (stage IIIB), these procedures are usually indicated because they represent the easiest way to confirm the diagnosis of lung cancer. When the clinical presentation is otherwise not consistent with locally advanced disease, the etiology of these lesions must be established in order to accurately define the stage. However, the procedures used to diagnose an enlarged supraclavicular node (needle aspiration or surgical biopsy) are the same regardless of whether the issue is to confirm the diagnosis or to define the stage. Similarly, in patients with a clinical presentation consistent with advanced disease (stage IV), an invasive procedure may be indicated as the easiest way to confirm the diagnosis and establish the cell type of lung cancer. In patients with a solitary site that is suspicious for a distant metastasis, or in patients with a clinical presentation that seems inconsistent with advanced disease, an invasive procedure is indicated to accurately define the stage. The procedures used to assess possible distant sites are the same regardless of the clinical presentation, and are dictated primarily by technical and anatomic factors specific to the particular patient.

No data are available to assess the sensitivity, specificity, and FN and FP rates of needle aspiration of a supraclavicular node. General experience indicates that this procedure is usually successful; in addition, surgical biopsy of such a node is easily accomplished if a needle aspiration is not diagnostic. The reliability of procedures to diagnose a pleural effusion is covered in the chapter on diagnosis. Thoracentesis has a sensitivity of approximately 60%; thoracoscopy has a sensitivity of > 95%. Procedures to diagnose suspected distant metastatic sites are too varied to discuss in detail; furthermore, no data are available that expressly assesses the reliability of these tests in patients with lung cancer.


   Clinical Questions
TOP
 Abstract
 Introduction
 Techniques of Invasive...
 Clinical Questions
Summary
 Summary of Recommendations
 References
 
Comparison of tests for mediastinal staging is difficult because the question being addressed is not always the same for patients undergoing one procedure vs another. For example, invasive staging may be performed primarily to confirm the diagnosis in a patient in which there is little doubt as to the presence of mediastinal involvement. In other patients, the issue may be to confirm that the mediastinum is not involved (ie, in instances where the FN rate of radiologic staging alone is unacceptably high), or to prove that mediastinal involvement is present (ie, in instances where the FP rate of radiologic staging alone is unacceptably high).

The population of patients undergoing one type of invasive procedure is usually different from the population undergoing another invasive test. For example, patients undergoing mediastinoscopy often have radiographically normal-appearing mediastinal lymph nodes, whereas those who undergo TBNA almost exclusively have enlarged nodes. Furthermore, a particular test may be selected because the lymph nodes in question are easily accessible by that technique and not by others. These issues must be kept in mind when evaluating invasive staging tests. A summary of some of the most important features of invasive tests is shown in Table 4 .


View this table:
[in this window]
[in a new window]

  		Table 4. Comparison of Characteristics of Invasive Tests

 
When the clinical question is to confirm the presumptive diagnosis of lung cancer and establish the cell type (ie, the presence of mediastinal node involvement is already clear based on radiographic imaging), the determining factors in selection of a test will be the sensitivity, the ability to perform the procedure in that particular patient, and the morbidity of the procedure. Procedures that can be performed on an outpatient basis and that carry a low risk of complications have a definite advantage. Mediastinoscopy and the Chamberlain procedure are less desirable because of a risk (albeit low) of significant complications. TTNA carries a relatively high risk of a pneumothorax requiring a tube for evacuation. These considerations make TBNA or EUS-NA good choices. The sensitivity of EUS-NA is particularly appealing. However, in the end, despite these considerations, the determining factors in selecting a diagnostic test are likely to be the local availability of expertise with particular procedures, as well as the location of suspicious nodes and their accessibility to biopsy by a particular technique.

However, in many instances in which there is mediastinal node enlargement, it is necessary to more accurately stage the mediastinum due to a high FP rate of the CT. In this situation both the sensitivity of the test as well as a low FN rate are important. Furthermore, it is usually also important to assess a number of mediastinal node stations in order to have a detailed assessment of the extent of mediastinal disease in these situations. Mediastinoscopy provides high sensitivity, a low FN rate, and the ability to assess most of the clinically important node stations. EUS-NA, if available, is a reasonable alternative whenever the nodes in question are accessible to this technique. TBNA is less appealing due to the lower sensitivity, but may be reasonable in some situations, particularly if bronchoscopy is indicated in the patients for other reasons. TTNA is also less appealing because of the risk of pneumothorax. It is important to note, however, that because of the high FN rate of EUS-NA, TBNA, or TTNA, a negative result of these tests in a patient with radiographically suspicious nodes should be followed up with further tests such as mediastinoscopy.

In situations where the major question is to confirm that there is no malignant involvement of mediastinal nodes, a test with a low FN rate is needed. In addition, a test is needed that allows as thorough an assessment of mediastinal node stations as possible. In this case, TTNA, TBNA, and EUS-NA have little role because of the high FN rates and poor ability to assess all of the mediastinal node stations. The "gold standard" is still mediastinoscopy, which allows sampling of multiple nodal stations in a reliable fashion. The exceptions are nodes in the inferior pulmonary ligament (which are rarely involved, even in the case of lower lobe tumors), APW nodes (which can be accessed via the Chamberlain procedure in the case of LUL tumors), and occasionally posterior subcarinal nodes. The same arguments in favor of mediastinoscopy apply when the issue is to rule out involvement of contralateral lymph nodes, for example, if patients with stage IIIA but not stage IIIB NSCLC are considered eligible for a trimodality treatment approach.

How positron emission tomography (PET) scanning should be integrated into the diagnosis and staging of lung cancer is still being defined. This is discussed further in the chapter on noninvasive staging. In general, the currently available data indicates that a PET scan that is positive in the mediastinum should be confirmed. It would stand to reason that the confirmatory test of a positive PET scan be one that provides access to the node station or stations that were positive on the PET scan. Furthermore, the confirmatory test should have a low FN rate. Based on these considerations, mediastinoscopy appears to be generally the best invasive test. It is unclear whether and under what circumstances a PET scan that is negative in the mediastinum should be confirmed (see discussion in the noninvasive staging chapter). If confirmation of a negative mediastinal PET is deemed necessary, mediastinoscopy is usually the best choice because of the low FN rate.

Recommendations

  1. In patients who have extensive mediastinal infiltration with tumor (T4 involvement or involvement to the point of not being able to see discrete lymph nodes), the primary goal of an invasive procedure is to provide confirmation of the diagnosis. (The radiographic staging of mediastinal node involvement is compelling.)
    For these patients, TTNA and EUS-NA are procedures of choice based on high sensitivity (approximately 90%) and low morbidity (outpatient procedure). Level of evidence, fair; benefit, moderate; grade of recommendation, B
    For these patients, TBNA is an alternative with appropriately located mediastinal involvement, but in general has lower sensitivity (approximately 75%) and occasional FP results. Level of evidence, fair; benefit, moderate; grade of recommendation, B
    For these patients, mediastinoscopy is least useful because of higher morbidity than EUS-NA, TTNA, and TBNA (although it is also an outpatient procedure). Level of evidence, fair; benefit, moderate; grade of recommendation, B
  2. In patients suspected of having NSCLC, who have no evidence of distant metastases, and who have enlarged, discrete mediastinal nodes by CT (because of a high FP rate of CT), mediastinoscopy is the invasive procedure of choice to rule in mediastinal node involvement.
    This recommendation is based on the ability of mediastinoscopy to stage most of the commonly involved mediastinal node stations with a presumed low FP rate, a low FN rate (approximately 10%) and low morbidity (2%; outpatient procedure). Level of evidence, fair; benefit, substantial; grade of recommendation, B
    For these patients, TBNA, TTNA, and EUS-NA are alternatives to mediastinoscopy, but result in less thorough mediastinal staging because of difficulty in assessing as many node stations and because of a higher FN rate. Level of evidence, fair; benefit, moderate; grade of recommendation, B
    For the subset of these patients with LUL cancer, the Chamberlain procedure, extended cervical mediastinoscopy, EUS-NA, or thoracoscopy to evaluate the APW nodes should also be performed if other mediastinal node stations are found to be uninvolved. Level of evidence, fair; benefit, moderate; grade of recommendation, B
  3. In patients suspected of having NSCLC, who have no evidence of distant metastases, and who have normal mediastinal nodes by CT, but in whom invasive staging of the mediastinum is recommended (because of a high FN rate of CT), mediastinoscopy is the invasive procedure of choice to rule out mediastinal node involvement.
    This recommendation is based on the ability of mediastinoscopy to stage most of the commonly involved mediastinal node stations with a low FN rate (approximately 10%) and low morbidity (2%; outpatient procedure). Level of evidence, fair; benefit, substantial; grade of recommendation, B
    For these patients, TBNA, TTNA, and EUS-NA are not recommended because of a high FN rate. Level of evidence, fair; benefit, none/negative; grade of recommendation, D
    For the subset of these patients who have a LUL cancer, the Chamberlain procedure, extended cervical mediastinoscopy, or thoracoscopy should be additionally performed to evaluate the APW nodes. Level of evidence, fair; benefit, moderate; grade of recommendation, B
  4. In patients with a PET scan that is positive in the mediastinum, confirmation should be obtained by an invasive test that allows sampling of the PET-positive nodes with a high sensitivity and a low FN rate. In general, mediastinoscopy is likely to be the best test. Level of evidence, fair; benefit, moderate; grade of recommendation, B
  5. In patients with a PET scan finding that is negative in the mediastinum, in whom confirmation of the absence of mediastinal involvement is deemed desirable, mediastinoscopy is generally the best test because of a low FN rate. Level of evidence, poor; benefit, moderate; grade of recommendation, C


   Summary
TOP
 Abstract
 Introduction
 Techniques of Invasive...
 Clinical Questions
 Summary
Summary of Recommendations
 References
 
In clinical practice, the diagnosis and staging of patients suspected of having lung cancer are closely linked and often proceed simultaneously. Invasive tests are sometimes used to confirm the presumed diagnosis, while at other times they are used to confirm the presumed stage. It is important to be clear about what the primary question is when assessing the value of invasive tests for a particular clinical scenario.

In patients with extensive mediastinal infiltration, the primary issue is confirmation of the diagnosis, because the stage is clearly defined radiographically. Sputum analysis, bronchoscopy (discussed in more detail in another chapter), TTNA, EUS-NA, and possibly TBNA are generally the most useful invasive tests. In patients without distant metastases but with discrete, enlarged mediastinal lymph nodes, the primary goal is to confirm the stage, because of the high FP rate of this finding on a CT scan. In general mediastinoscopy is the best invasive procedure, because it allows a thorough staging to be carried out. TBNA, TTNA, and EUS-NA may be an alternative, depending on the location of the lymph nodes and the availability of expertise with these procedures.

In patients without distant metastases and with normal mediastinal nodes by CT scan, but who have a central tumor, an adenocarcinoma or evidence of hilar node involvement, the issue is also to confirm the presumed stage because of a high FN rate of the CT scan for mediastinal node involvement in these settings. The primary role of an invasive test is to rule out malignant involvement. Mediastinoscopy is the procedure of choice, because of the low FN rate of this procedure.

The most appropriate use of PET scanning for staging of the mediastinum is still being defined. A positive PET scan result in the mediastinum should be confirmed by a test that allows access to the suspicious nodes. It is controversial whether a negative PET scan result in the mediastinum is adequate in settings with a relatively high rate of mediastinal involvement despite a negative CT (central tumor, adenocarcinoma, or evidence of hilar involvement). The FN rate of PET in this specific setting has not been defined. If confirmation of a negative PET scan result in the mediastinum is necessary, mediastinoscopy is the best test.


   Summary of Recommendations
TOP
 Abstract
 Introduction
 Techniques of Invasive...
 Clinical Questions
 Summary
 Summary of Recommendations
References
 

  1. In patients who have extensive mediastinal infiltration with tumor (T4 involvement or involvement to the point of not being able to see discrete lymph nodes), the primary goal of an invasive procedure is to provide confirmation of the diagnosis. (The radiographic staging of mediastinal node involvement is compelling.)
    For these patients, TTNA and EUS-NA are procedures of choice based on high sensitivity (approximately 90%) and low morbidity (outpatient procedure). Level of evidence, fair; benefit, moderate; grade of recommendation, B
    For these patients, TBNA is an alternative with appropriately located mediastinal involvement, but in general has lower sensitivity (approximately 75%) and occasional FP results. Level of evidence, fair; benefit, moderate; grade of recommendation, B For these patients, mediastinoscopy is least useful because of higher morbidity than EUS-NA, TTNA, and TBNA (although it is also an outpatient procedure). Level of evidence, fair; benefit, moderate; grade of recommendation, B
  2. In patients suspected of having NSCLC, who have no evidence of distant metastases, and who have enlarged, discrete mediastinal nodes by CT (because of a high FP rate of CT), mediastinoscopy is the invasive procedure of choice to rule in mediastinal node involvement.
    This recommendation is based on the ability of mediastinoscopy to stage most of the commonly involved mediastinal node stations with a presumed low FP rate, a low FN rate (approximately 10%), and low morbidity (2%; outpatient procedure). Level of evidence, fair; benefit, substantial; grade of recommendation, B
    For these patients, TBNA, TTNA, and EUS-NA are alternatives to mediastinoscopy, but result in less thorough mediastinal staging because of difficulty in assessing as many node stations and because of a higher FN rate. Level of evidence, fair; benefit, moderate; grade of recommendation, B
    For the subset of these patients with a LUL cancer, the Chamberlain procedure, extended cervical mediastinoscopy, EUS-NA, or thoracoscopy to evaluate the APW nodes should also be performed if other mediastinal node stations are found to be uninvolved. Level of evidence, fair; benefit, moderate; grade of recommendation, B
  3. In patients suspected of having NSCLC, who have no evidence of distant metastases, and who have normal mediastinal nodes by CT, but in whom invasive staging of the mediastinum is recommended (because of a high FN rate of CT), mediastinoscopy is the invasive procedure of choice to rule out mediastinal node involvement.
    This recommendation is based on the ability of mediastinoscopy to stage most of the commonly involved mediastinal node stations with a low FN rate (approximately 10%) and low morbidity (2%; outpatient procedure). Level of evidence, fair; benefit, substantial; grade of recommendation, B
    For these patients, TBNA, TTNA, and EUS-NA are not recommended because of a high FN rate. Level of evidence, fair; benefit, none/negative; grade of recommendation, D
    For the subset of these patients who have LUL cancer, the Chamberlain procedure, extended cervical mediastinoscopy, or thoracoscopy should be additionally performed to evaluate APW nodes. Level of evidence, fair; benefit, moderate; grade of recommendation, B
  4. In patients with a PET scan result that is positive in the mediastinum, confirmation should be obtained by an invasive test that allows sampling of the PET-positive nodes with a high sensitivity and a low FN rate. In general, mediastinoscopy is likely to be the best test. Level of evidence, fair; benefit, moderate; grade of recommendation, B
  5. In patients with a PET scan result that is negative in the mediastinum, in whom confirmation of the absence of mediastinal involvement is deemed desirable, mediastinoscopy is generally the best test because of a low FN rate. Level of evidence, poor; benefit, moderate; grade of recommendation, C


   Footnotes
 
Abbreviations: APW = aortopulmonary window; EUS-NA = endoscopic ultrasound and needle aspiration; FN = false-negative; FP = false-positive; LUL = left upper lobe; NSCLC = non-small cell lung cancer; PET = positron emission tomography; SCLC = small cell lung cancer; TBNA = transbronchial needle aspiration; TTNA = transthoracic needle aspiration; VATS = video-assisted thoracic surgery

The work for these guidelines was performed at the University of North Carolina at Chapel Hill.


   References
TOP
 Abstract
 Introduction
 Techniques of Invasive...
 Clinical Questions
 Summary
 Summary of Recommendations
 References
 

  1. Cybulsky, IJ, Bennett, WF (1994) Mediastinoscopy as a routine outpatient procedure. Ann Thorac Surg 58,176-178[Abstract]
  2. Vallières, EA, Pagé, A, Verdant, A Ambulatory mediastinoscopy and anterior mediastinotomy. Ann Thorac Surg 1991;52,1122-1126[Abstract]
  3. Selby, JH, Jr, Leach, CL, Heath, BJ, et al Local anesthesia for mediastinoscopy: experience with 450 consecutive cases. Am Surg 1978;44,679-682[ISI][Medline]
  4. Kiser, AC, Detterbeck, FC General aspects of surgical treatment. Detterbeck, FC Rivera, MP Socinski, MAet al eds. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. 2001,133-147 W. B. Saunders Philadelphia, PA.
  5. 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]
  6. Staples, CA, Muller, NL, Miller, RR, et al Mediastinal nodes in bronchogenic carcinoma: comparison between CT and mediastinoscopy. Radiology 1988;167,367-372[Abstract]
  7. Gdeedo, A, Van Schil, P, Corthouts, B, et al Prospective evaluation of computed tomography and mediastinoscopy in mediastinal lymph node staging. Eur Respir J 1997;10,1547-1551[Abstract]
  8. Van den Bosch, JMM, Gelissen, HJ, Wagenaar, SS Exploratory thoracotomy in bronchial carcinoma. Thorac Cardiovasc Surg 1983;85,733-737
  9. Hammoud, ZT, Anderson, RC, Meyers, BF, et al The current role of mediastinoscopy in the evaluation of thoracic disease. Thorac Cardiovasc Surg 1999;118,894-899
  10. Patterson, GA, Piazza, D, Pearson, FG, et al Significance of metastatic disease in subaortic lymph nodes. Ann Thorac Surg 1987;43,155-159[Abstract]
  11. Detterbeck, FC, Jones, DR Surgical treatment of stage IIIa (N2) non-small cell lung cancer. Detterbeck, FC Rivera, MP Socinski, MAet al eds. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. 2001,244-256 W.B. Saunders Philadelphia, PA.
  12. Jiao, J, Magistrelli, P, Goldstraw, P The value of cervical mediastinoscopy combined with anterior mediastinotomy in the preoperative evaluation of bronchogenic carcinoma of the left upper lobe. Eur J Cardiothorac Surg 1997;11,450-454[Abstract]
  13. Best, LA, Munichor, M, Ben-Shakhar, M, et al The contribution of anterior mediastinotomy in the diagnosis and evaluation of diseases of the mediastinum and lung. Ann Thorac Surg 1987;43,78-81[Abstract]
  14. Ginsberg, RJ, Rice, TW, Goldberg, M, et al Extended cervical mediastinoscopy: a single staging procedure for bronchogenic carcinoma of the left upper lobe. Thorac Cardiovasc Surg 1987;94,673-678
  15. Freixinet Gilart, J, Garcia, PG, de Castro, FR, et al Extended cervical mediastinoscopy in the staging of bronchogenic carcinoma. Ann Thorac Surg 2000;70,1641-1643[Abstract/Free Full Text]
  16. Urschel, JD, Vretenar, DF, Dickout, WJ, et al Cerebrovascular accident complicating extended cervical mediastinoscopy. Ann Thorac Surg 1994;57,740-741[Abstract]
  17. Lopez, L, Varela, A, Freixinet, J, et al Extended cervical mediastinoscopy: prospective study of fifty cases. Ann Thorac Surg 1994;57,555-557[Abstract]
  18. Ginsberg, RJ Discussion of: Lopez L, Varela A, Freixinet J, et al: Extended cervical mediastinoscopy: prospective study of fifty cases. Ann Thorac Surg 1994;57,555-558[Abstract]
  19. Landreneau, RJ, Hazelrigg, SR, Mack, MJ, et al Thoracoscopic mediastinal lymph node sampling: useful for mediastinal lymph node stations inaccessible by cervical mediastinoscopy. Thorac Cardiovasc Surg 1993;106,554-558
  20. Detterbeck, FC, Jones, DR, Parker, LA, Jr Intrathoracic staging. Detterbeck, FC Rivera, MP Socinski, MAet al eds. Diagnosis and treatment of lung cancer: an evidence-based guide for the practicing clinician. 2001,73-93 W.B. Saunders Philadelphia, PA.
  21. Bilaceroglu, S, Cagiotariotaciota, U, Gunel, O, et al Comparison of rigid and flexible transbronchial needle aspiration in the staging of bronchogenic carcinoma. Respiration 1998;65,441-449[CrossRef][ISI][Medline]
  22. Vansteenkiste, J, Lacquet, LM, Demedts, M, et al Transcarinal needle aspiration biopsy in the staging of lung cancer. Eur Respir J 1994;7,265-268[Abstract]
  23. Rodríguez de Castro, F, Rey, A, Caminero, J, et al Transbronchial fine needle aspiration in clinical practice. Cytopathology 1995;6,22-29[ISI][Medline]
  24. Garpestad, E, Goldberg, S, Herth, F, et al CT fluoroscopy guidance for transbronchial needle aspiration: an experience in 35 patients. Chest 2001;119,329-332[Abstract/Free Full Text]
  25. Gress, FG, Savides, TJ, Sandler, A, et al Endoscopic ultrasonography, fine-needle aspiration biopsy guided by endoscopic ultrasonography, and computed tomography in the preoperative staging of non-small-cell lung cancer: a comparison study. Ann Intern Med 1997;127,604-612[Abstract/Free Full Text]
  26. Fritscher-Ravens, A, Soehendra, N, Schirrow, L, et al Role of transesophageal endosonography-guided fine-needle aspiration in the diagnosis of lung cancer. Chest 2000;117,339-345[Abstract/Free Full Text]
  27. Silvestri, GA, Hoffman, BJ, Bhutani, MS, et al Endoscopic ultrasound with fine-needle aspiration in the diagnosis and staging of lung cancer. Ann Thorac Surg 1996;61,1441-1446[Abstract/Free Full Text]
  28. Wiersema, MJ, Vazquez-Sequeiros, E, Wiersema, LM Evaluation of mediastinal lymphadenopathy with endoscopic US-guided fine-needle aspiration biopsy. Radiology 2001;219,252-257[Abstract/Free Full Text]
  29. Wallace, MB, Silvestri, GA, Sahai, AV, et al Endoscopic ultrasound-guided fine needle aspiration for staging patients with carcinoma of the lung. Ann Thorac Surg 2001;72,1861-1867[Abstract/Free Full Text]



This article has been cited by other articles:


Home page
 ChestHome page
V. Bandi, W. Lunn, A. Ernst, R. Eberhardt, H. Hoffmann, and F. J. F. Herth
Ultrasound vs CT in Detecting Chest Wall Invasion by Tumor: A Prospective Study
Chest, April 1, 2008; 133(4): 881 - 886.
[Abstract] [Full Text] [PDF]

Home page
 ChestHome page
N. M. Patel, A. Pohlman, A. Husain, I. Noth, J. B. Hall, and J. P. Kress
Conventional Transbronchial Needle Aspiration Decreases the Rate of Surgical Sampling of Intrathoracic Lymphadenopathy
Chest, March 1, 2007; 131(3): 773 - 778.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
F. C. Detterbeck
Relearning the Lessons of the Past: Are We Making Progress?
Ann. Thorac. Surg., November 1, 2005; 80(5): 1979 - 1980.
[Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
M. A. Eloubeidi, A. Tamhane, V. K. Chen, and R. J. Cerfolio
Endoscopic Ultrasound-Guided Fine-Needle Aspiration in Patients With Non-Small Cell Lung Cancer and Prior Negative Mediastinoscopy
Ann. Thorac. Surg., October 1, 2005; 80(4): 1231 - 1239.
[Abstract] [Full Text] [PDF]

Home page
 JAMAHome page
J. T. Annema, M. I. Versteegh, M. Veselic, L. Welker, T. Mauad, J. K. Sont, L. N. A. Willems, and K. F. Rabe
Endoscopic Ultrasound Added to Mediastinoscopy for Preoperative Staging of Patients With Lung Cancer
JAMA, August 24, 2005; 294(8): 931 - 936.
[Abstract] [Full Text] [PDF]

Home page
 Eur. J. Cardiothorac. Surg.Home page
J. Kuzdzal, M. Zielinski, B. Papla, A. Szlubowski, L. Hauer, T. Nabialek, W. Sosnicki, and J. Pankowski
Transcervical extended mediastinal lymphadenectomy--the new operative technique and early results in lung cancer staging
Eur. J. Cardiothorac. Surg., March 1, 2005; 27(3): 384 - 390.
[Abstract] [Full Text] [PDF]

Home page
 Ann. Thorac. Surg.Home page
M. A. Eloubeidi, R. J. Cerfolio, V. K. Chen, R. Desmond, S. Syed, and B. Ojha
Endoscopic Ultrasound-Guided Fine Needle Aspiration of Mediastinal Lymph Node in Patients With Suspected Lung Cancer After Positron Emission Tomography and Computed Tomography Scans
Ann. Thorac. Surg., January 1, 2005; 79(1): 263 - 268.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
B. C. Jacobson, M. K. Gould, G. A. Silvestri, F. Detterbeck, A. Papagiannis, A. Buyukcelik, B. Yalcin, G. Utkan, A. Spira, and D. S. Ettinger
Multidisciplinary Management of Lung Cancer
N. Engl. J. Med., May 6, 2004; 350(19): 2008 - 2010.
[Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF) Free
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Article Archive
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Detterbeck, F. C.
Right arrow Articles by Silvestri, G. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Detterbeck, F. C.
Right arrow Articles by Silvestri, G. A.

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS