Although mediastinoscopy/otomy has the distinct advantage of providing direct visualization of suspicious mediastinal nodal disease, as well as a tissue diagnosis of such nodes, other studies are available in the preoperative staging repertoire. A noninvasive imaging modality currently in clinical use to evaluate for hilar, mediastinal, and extrathoracic metastases is positron-emission tomography (PET). By using the radioisotope [18F]fluorodeoxyglucose (FDG) to detect metabolically overactive cellular growth, one can more accurately describe a patient's clinical stage and appropriate therapeutic maneuvers.
There is currently no absolute indication for the use of PET scanning, although some guidelines do exist in the literature. It seems clear that for patients who display clear evidence of extrathoracic disease, PET scanning is a costly and unnecessary test that will not change clinical management. Generally, a PET scan is indicated for patients with a question of extrathoracic metastases, those with questionable clinical stage III (cIII) disease (and even cI and cII disease), because surgical management may be altered in at least 8% to 18% of these patients.6,7
The data to support these clinical recommendations are substantial. PET scans, when compared with CT scans of the chest, abdomen, and pelvic anatomy, have an increased sensitivity for detecting disease, ranging from 79% to 95% versus 50% to 86% for CT.8–10 The significance of this is most noticeable in light of evidence that 7.5%, 18%, and 24% of patients with cI, cII, and cIII disease, respectively, will have extrathoracic disease by PET scanning and hence may avoid an unnecessary nontherapeutic resection.11 The strengths of PET scanning lie in its superior sensitivity and accuracy (>90%).12 This has led many to provide recommendations about continued operative staging (i.e., mediastinoscopy) depending on PET and CT scanning. Surgical staging may not be necessary in patients with negative CT and PET,13 negative PET and mediastinal nodes less than 1.5 cm,14 or if the primary lesion has a PET standardized uptake value (SUV) of less than 2.5 and a negative mediastinum.15
Although it has excellent sensitivity, the specificity of PET scanning is unacceptably low. A number of inflammatory and infectious conditions can produce a positive PET scan in the absence of malignancy, thus leading to either unnecessary operative diagnostic procedures or, worse yet, a decision to forego definitive treatment because of a false assumption of metastatic disease (overstaging). This is critical because there are data to suggest that even minimal N2 disease (e.g., ipsilateral mediastinal nodal metastases) can be resected with a primary tumor for a 5-year survival rate of 40% compared with 8% for bulky N2 disease.11 In addition, since several studies have demonstrated high false-negative and false-positive rates (11%–33% and 15%–52%, respectively, with PET), surgical staging continues to be an important part of the preoperative workup.
Endobronchial Ultrasound and Endoscopic Esophageal Ultrasound in Mediastinal Staging
The introduction of endobronchial ultrasound (EBUS) and endoscopic esophageal ultrasound (EUS) has aided clinicians in determining appropriate candidates for surgical versus nonoperative therapy for lung cancer in a less invasive manner. Endobronchial ultrasound with transbronchial FNA (EBUS-TBNA) can be used to biopsy lymph nodes in stations 1 to 4, 7, and 10 to 12. Accuracy rates of over 90% have been reported by the combined use of EBUS and EUS-FNA biopsy to stage the mediastinum in NSCLC.16
To describe the technique of EUS briefly, an endoscope is inserted into the esophagus with sonographic examination of nodal tissue distributed around the esophagus. By passing the endoscope distally, one can assess adrenal lesions and, more frequently, posterior mediastinal lymph nodes, most notably stations 7, 8, and 9. Level 5 nodes in the aortopulmonary window can be accessed, as well as occasionally the levels 2 and 4 paratracheal nodes. In contrast with PET, nodes as small as 3 mm can be visualized, and those 5 mm or larger may be biopsied.17 The only inaccessible mediastinal nodes are those anterior to the tracheobronchial tree (levels 2, 3, and 4) because air within the proximal airway distorts ultrasound findings.
EUS with FNA has gained considerable acceptance as an adjunct to mediastinoscopy, particularly in evaluating posterior mediastinal nodes at levels 5, 7, 8, and 9. Recent data suggest that EUS with FNA is superior to any other technique in investigating the posterior mediastinum, with sensitivity of 84% to 94%, specificity of 100%, and accuracy of 94% to 98% in determining regional disease.18–21
Some have advocated the use of EBUS-TBNA and EUS-FNA as a primary method of staging the mediastinum. This method can be supported by its minimally invasive approach and relatively low risk, coupled with its ability to provide accurate, thorough information about locoregional and distant disease. A randomized controlled multicenter trial assigned 241 patients to either surgical staging alone or combined EBUS-TBNA and EUS-FNA followed by surgical staging if no nodal metastases were found. For patients without evidence of mediastinal metastases following surgical staging in either group, a thoracotomy with complete lymph node dissection was done. This study found that EBUS-TBNA and EUS-FNA improved the detection of nodal metastases and reduced the number of unnecessary thoracotomies by more than half compared with surgical staging alone.22 In a recent prospective trial, EBUS-TBNA and mediastinoscopy were performed in the same setting in 153 patients, and thoracotomy with pulmonary resection and mediastinal lymphadenectomy were performed on those patients for whom no evidence of N2 or N3 disease was found on EBUS-TBNA or mediastinoscopy.23 EBUS-TBNA was found to have no statistical difference in sensitivity, negative predictive value, and diagnostic accuracy compared to mediastinoscopy.24 In fact, such data are so encouraging that some centers have suggested replacing mediastinoscopy with EBUS-TBNA and EUS-FNA as the “gold standard” for staging the mediastinum.
Enthusiasm for EBUS/EUS used either alone or in conjunction with currently accepted surgical staging techniques must be tempered by a number of factors. Much of the current data supporting EBUS/EUS has been compiled at advanced tertiary care centers with significant experience in the technique. The assessment of tissue (mediastinoscopy) versus cytology (EBUS/EUS) also may factor into the accuracy of detecting micrometastases, as well as the ability to provide adequate tissue for tumor marker and mutation analysis.