Chest
Volume 132, Issue 3, Supplement, September 2007, Pages 178S-201S
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DIAGNOSIS AND MANAGEMENT OF LUNG CANCER: ACCP GUIDELINES (2ND EDITION)
Noninvasive Staging of Non-small Cell Lung Cancer: ACCP Evidenced-Based Clinical Practice Guidelines (2nd Edition)

https://doi.org/10.1378/chest.07-1360Get rights and content

Background

Correctly staging lung cancer is important because the treatment options and the prognosis differ significantly by stage. Several noninvasive imaging studies including chest CT scanning and positron emission tomography (PET) scanning are available. Understanding the test characteristics of these noninvasive staging studies is critical to decision making.

Methods

Test characteristics for the noninvasive staging studies were updated from the first iteration of the lung cancer guidelines using systematic searches of the MEDLINE, HealthStar, and Cochrane Library databases up to May 2006, including selected metaanalyses, practice guidelines, and reviews. Study designs and results are summarized in evidence tables.

Results

The pooled sensitivity and specificity of CT scanning for identifying mediastinal lymph node metastasis were 51% (95% confidence interval [CI], 47 to 54%) and 85% (95% CI, 84 to 88%), respectively, confirming that CT scanning has limited ability either to rule in or exclude mediastinal metastasis. For PET scanning, the pooled estimates of sensitivity and specificity for identifying mediastinal metastasis were 74% (95% CI, 69 to 79%) and 85% (95% CI, 82 to 88%), respectively. These findings demonstrate that PET scanning is more accurate than CT scanning. If the clinical evaluation in search of metastatic disease is negative, the likelihood of finding metastasis is low.

Conclusions

CT scanning of the chest is useful in providing anatomic detail, but the accuracy of chest CT scanning in differentiating benign from malignant lymph nodes in the mediastinum is poor. PET scanning has much better sensitivity and specificity than chest CT scanning for staging lung cancer in the mediastinum, and distant metastatic disease can be detected by PET scanning. With either test, abnormal findings must be confirmed by tissue biopsy to ensure accurate staging.

Section snippets

Selection Criteria

Titles and abstracts, and the full text of all articles passing the title-and-abstract screen were evaluated independently by at least two of the authors for inclusion or exclusion based on the following five criteria: (1) publication in a peer-reviewed journal; (2) study size of 20 patients (except for studies involving CT scan evaluation of the mediastinum, for which 50 patients were required); (3) patient group not included in a subsequent update of the study; (4) histologic or cytologic

Grading Recommendations

Recommendations were developed by the writing committee, graded by a standardized method (see the “Methodology for Lung Cancer Evidence Review and Guideline Development” chapter), and reviewed by all members of the lung cancer panel prior to approval by the Thoracic Oncology Network, Health and Science Policy Committee, and the Board of Regents of the American College of Chest Physicians.

Noninvasive Staging of the Mediastinum

Staging is a critical part of the evaluation of every patient with lung cancer. Defining malignant involvement of the mediastinal lymph nodes is particularly important, as the status of these nodes will in many cases determine whether there is surgically resectable disease. the clinical staging of lung cancer is usually directed by noninvasive imaging modalities. On the basis of such tests, clinicians will determine the likelihood of the presence or absence of tumor involvement in regional

Chest Radiograph

The majority of lung cancers are initially detected on a plain chest radiograph. In some situations, the plain radiograph may be sufficient to detect spread of the tumor to the mediastinum. For example, the presence of bulky lymphadenopathy in the superior or contralateral mediastinal areas may be considered adequate evidence of metastatic disease, precluding a further imaging evaluation of the chest. This may be particularly true if the patient is too ill or is unwilling to undergo treatment

CT Scan of the Chest

CT scanning of the chest is the most widely available and commonly used noninvasive modality for evaluation of the mediastinum in lung cancer. The vast majority of reports evaluating accuracy of CT scanning for mediastinal lymph node staging have employed the administration of IV contrast material. IV contrast is not absolutely necessary in performing chest CT scanning for this indication, but may be useful in helping to distinguish vascular structures from lymph nodes as well as in delineating

Recommendations

  • 1

    For patients with either a known or suspected lung cancer who are eligible for treatment, a CT scan of the chest with contrast including the upper abdomen (liver and adrenal glands) should be performed. Grade of recommendation, 1B

  • 2

    In patients with enlarged discrete mediastinal lymph nodes on CT scans (> 1 cm on the short axis) and no evidence of metastatic disease, further evaluation of the mediastinum should be performed prior to definitive treatment of the primary tumor. Grade of

PET Scanning

PET scanning is an imaging modality based on the biological activity of neoplastic cells. Lung cancer cells demonstrate increased cellular uptake of glucose and a higher rate of glycolysis when compared to normal cells.49 The radiolabeled glucose analog 18F-fluoro-2-deoxy-D-glucose (FDG) undergoes the same cellular uptake as glucose and is phosphorylated by hexokinase, generating 18F-FDG-6-phosphate. The combination of increased uptake of 18F-FDG and a decreased rate of dephosphorylation by

Recommendations

  • 3

    PET scanning to evaluate for mediastinal and extrathoracic staging should be considered in patients with clinical 1A lung cancer being treated with curative intent. Grade of recommendation, 2C

  • 4

    Patients with clinical 1B-IIIB lung cancer being treated with curative intent, should undergo PET scanning (where available) for mediastinal and extrathoracic staging. Grade of recommendation, IB

  • 5

    In patients with an abnormal result on FDG-PET scans, further evaluation of the mediastinum with sampling of the

Integrated PET and CT Scanning

An important shortcoming of dedicated PET imaging is its limited spatial resolution, which results in poor definition of anatomic structures. As a result, it may be difficult for PET scanning to distinguish between mediastinal and hilar lymph nodes, or to differentiate between a central primary tumor and a lymph node metastasis, even when the results of PET and CT scans are visually correlated. This limitation has been addressed by the development of “dual-modality” or “integrated” PET/CT

MRI for Staging the Mediastinum

Like CT scanning, MRI is an anatomic study. Data relating to the accuracy of the evaluation of the mediastinum with MRI in patients with NSCLC are limited, but available reports13, 86 suggest that the accuracy of MRI is as good as CT scanning. Two reports86, 87 also have suggested that the use of contrast enhancement may improve the accuracy of MRI in this situation. MRI may be superior to CT scanning for defining lung cancer spread in the thorax in specific situations. Because MRI can detect

Recommendation

  • 6

    For patients with either a known or suspected lung cancer who are eligible for treatment, an MRI of the chest should not routinely be performed for staging the mediastinum. MRI may be useful in patients with NSCLC where there is concern for involvement of the superior sulcus or brachial plexus involvement. Grade of recommendation, 1B

The Search for Metastatic Disease

The purpose of extrathoracic scanning in patients with NSCLC is usually to detect metastatic disease, especially at common metastatic sites such as the adrenal glands, liver, brain, and skeletal system, thereby sparing the patient fruitless radical treatment.92 However, scans can only detect macroscopic metastatic deposits that have reached a size within the resolution capability of the imaging modality in question, and this can be considered a major shortcoming of all conventional tests

Utility of PET Scanning for Detecting Metastatic Disease

Since 1993, numerous studies have assessed the clinical utility of PET scans to assist in the search for metastatic disease in patients with NSCLC. In general, these tend to be relatively small, prospective, single-institution assessments in which whole-body PET scanning suggests the presence of unsuspected distant disease in 10 to 20% of cases.20, 27, 121, 122 The yield of unsuspected metastases depends on a number of factors, including whether PET scanning is gauged as an initial metastatic

Detection of Abdominal Metastases

Some PET scan studies can also be considered in the context of the scanning of individual organ systems in patients with NSCLC. Thirteen studies105, 106, 107, 109, 133, 134, 135, 136, 137, 138, 139, 140, 141 evaluated the utility of clinical evaluation in detecting abdominal metastases in 1,291 patients using CT scanning as the reference standard (Table 5). Most of the studies limited study enrollment to patients with a negative clinical evaluation. In these nine studies,107, 109, 133, 134, 135

Detection of Brain Metastases

In most studies, the yield of CT scanning/MRI of the brain in NSCLC patients with negative clinical examination findings is 0 to 10%,152, 153, 154, 155, 156, 157, 158 possibly rendering the test cost-ineffective.154 Eighteen studies31, 100, 105, 107, 108, 109, 137, 152, 153, 155, 158, 159, 160, 161, 162, 163, 164 evaluated the ability of clinical evaluation to detect brain metastases in comparison to CT in 1,830 patients (Table 6). Nine studies31, 107, 137, 152, 153, 155, 158, 159, 164 limited

Detection of Bone Metastases

The problem of false-positive scan abnormalities in radionuclide bone scintigraphy is particularly nettlesome, owing to the frequency of degenerative and traumatic skeletal damage and the difficulty in obtaining a definitive diagnosis via follow-up imaging or biopsy. False-positive bone imaging findings also occur with MRI, which may be no more accurate than nuclear bone imaging.167 Eight studies examined the ability of the clinical evaluation to detect bone metastases in 723 patients using

Pleural/Lung Metastases

The limited data suggest that PET scanning can be useful in identifying lung metastases28, 174 and malignant pleural effusions175, 176 in NSCLC patients, though much of the data pertains to nonpulmonary malignancies. False-positive and false-negative findings have occasionally been noted.30, 175, 177, 178

Recommendations

  • 7

    For patients with either a known or suspected lung cancer, a thorough clinical evaluation similar to that listed in Table 4 should be performed. Grade of recommendation, 1B

  • 8

    Patients with abnormal clinical evaluations should undergo imaging for extrathoracic metastases. Site-specific symptoms warrant a directed evaluation of that site with the most appropriate study (eg , head CT scanning/MRI plus either whole-body PET scanning or bone scanning plus abdominal CT scanning). Grade of

Summary

CT scanning of the chest is useful in providing anatomic detail that better identifies the location of the tumor, its proximity to local structures, and whether or not lymph nodes in the mediastinum are enlarged. Unfortunately, the accuracy of chest CT scanning in differentiating benign from malignant lymph nodes in the mediastinum is unacceptably low. Whole-body PET scanning provides functional information on tissue activity, and has much better sensitivity and specificity than chest CT

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