Lung cancer remains the most common cause of cancer death in the United States. Accurate staging leads to optimal treatment decisions, defines prognosis,⁴ and mitigates the impact of inaccurate clinical staging upon the design of clinical research.¹ For limited-stage disease, mediastinal lymph node involvement is the most important factor determining both treatment method and prognosis.¹¹ CALGB 9761 confirms clinical underestimation of disease. Of patients suspected of having stage I non-small-cell lung cancer (NSCLC), only 61.7% retained that stage and diagnosis after complete staging. For patients with confirmed NSCLC, staging accuracy improved to 71.6% using multiple invasive and noninvasive diagnostic techniques.¹ Accurate mediastinal assessment leads to a lower probability of stage misclassification with “patients migrating toward their true (higher) stage,”¹⁷ sometimes termed the “Will Rogers phenomenon.” Despite advances in noninvasive radiologic anatomic and functional imaging as well as medical mediastinoscopy (endoscopic ultrasound–guided fine-needle aspiration [EUS-FNA] and endobronchial ultrasound–guided transbronchial needle aspiration [EBUS-TBNA]), mediastinoscopy remains the “gold standard” for the mediastinal staging of lung cancer, and video-mediastinoscopy allows for the standardization of technique.

Noninvasive CT scan assessment of the mediastinum is associated with high rates of false positives and false negatives. The Duke University Evidence-Based Practice Center investigators evaluated CT scan mediastinal staging. Pooled sensitivity and specificity of noninvasive mediastinal assessment with CT scan were 51% and 86% respectively, and 40% of lymph nodes interpreted as malignant by CT scan were benign. Up to 20% of lymph nodes interpreted as benign on CT scan were malignant.^12,13 Regarding mediastinal imaging by positron emission tomography (PET), the same investigators reported pooled sensitivity of 74% and specificity of 85% for detecting mediastinal metastasis.^12,13 The high false-negative and false-positive rates associated with
PET mediastinal imaging require tissue confirmation to prevent unnecessary surgical explorations as well as to prevent patients from being excluded from curative surgery. According to Melek and associates,¹⁰ PET does not provide enough “accuracy in mediastinal staging of NSCLC.” Lee and colleagues⁷ suggest that increasing the minimum standard uptake value (SUV) threshold for positive lymph nodes from 2.5 to 5.3 improves the sensitivity to 91% and specificity to 88% of PET mediastinal imaging. Caution must be exercised with this approach, as there may be a higher number of falsenegatives for patients harboring micrometastatic mediastinal lymphadenopathy.⁷ Further studies are necessary to validate utilization of a higher SUV in the staging of the mediastinum.¹⁶ Whitson and colleagues¹⁶ recommend tissue confirmation in all patients considered candidates for “definitive chemoradiation therapy or for surgical resection.” Endoscopic mediastinal assessment utilizing a combination of EUS-FNA and EBUS-TBNA is a promising strategy to assess the mediastinum in patients with lung cancer.

EUS and EBUS allows for the evaluation of levels 2R, 4R, 3, 2L, 4L, 7, 9, 10, 11, and 12. EUS-FNA has been shown to have high sensitivity (93%) and high negative predictive value (83%).¹⁴ Sensitivity (93%) remains high and negative predictive value increases to 97% when EUS-FNA is combined with EBUS-TBNA.¹⁵ Although more lymph node stations can be assessed utilizing EUS-FNA combined with EBUS-TBNA, Yasufuku and Fujisawa¹⁸ suggest that “due to the possibility of micrometastases, it is not clear that EBUS-TBNA will completely replace mediastinoscopy for mediastinal staging.” Randomized controlled trials are needed to evaluate endoscopic mediastinal staging versus mediastinoscopy.³