Key Point

Endobronchial plus transesophageal endoscopic ultrasound-guided fine-needle aspirations may be more accurate in detecting malignant lymph nodes than transbronchial needle aspiration, and it could be an alternative to mediastinoscopy.

Although mediastinoscopy is considered the diagnostic standard for the detection of malignant lymph nodes in patients with suspected lung cancer, less invasive alternatives to this procedure may also provide desirable accuracy. Among these minimally invasive options, the combination of endobronchial ultrasound-guided fine-needle aspiration (EBUS-FNA) and transesophageal endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) may be more accurate than traditional transbronchial needle aspiration (TBNA) and, in some cases, serve as a substitute for mediastinoscopy, as reported in the February 6 JAMA.

“Our study suggests that EBUS-FNA and EUS-FNA are more sensitive than standard TBNA and that EUS-FNA in combination with EBUS-FNA achieves near-complete minimally invasive mediastinal staging in patients with suspected lung cancer,” Michael B. Wallace, MD, and colleagues stated. “If these data are confirmed by other studies, they thus suggest that EUS plus EBUS may be an alternative method for surgical staging of the mediastinum.”

Dr. Wallace, Director of Research for the Department of Medicine and Professor of Medicine in the Division of Gastroenterology and Hepatology at the Mayo Clinic in Jacksonville, Florida, and colleagues enrolled 150 patients with suspected lung cancer for the study. Primary chest CT or PET images were unavailable for 12 of these patients, which excluded them from the final analysis. Among the remaining 138 patients, 42 had malignant lymph nodes. EUS-FNA detected malignant lymph nodes mostly in the subcarina and posterior mediastinum, while EBUS-FNA detected malignant lymph nodes mostly in the subcarina and anterior mediastinum.

EUS-FNA and EBUS-FNA each detected 29 malignant lymph nodes, while TBNA detected 15. However, the combination of EUS-FNA and EBUS-FNA (EUS plus EBUS) detected 39 malignant lymph nodes and displayed an estimated sensitivity that was 24% higher than that of either of these two methods alone. “EUS plus EBUS also had higher sensitivity and higher negative predictive value for detecting lymph nodes in any mediastinal location and for patients without lymph node enlargement on chest CT,” the researchers pointed out. In addition, EUS plus EBUS had a negative predictive value of 97%, which was higher than the negative predictive value of either of these two methods alone (88%). In comparison, TBNA had the lowest negative predictive value (78%).

BENEFITS OF EUS PLUS EBUS

Both EUS-FNA and EBUS-FNA separately have been shown to have good sensitivity among patients with suspected lung cancer. The present study’s results confirmed this and showed that “EBUS-FNA is more accurate than standard TBNA for the detection of malignant mediastinal lymph nodes,” Dr. Wallace and colleagues stated. However, the results also suggest that “EUS plus EBUS is more accurate than any of these procedures alone. In this study, this combination provided nearly complete staging (negative predictive value, 97%; positive predictive value, 100%) of the mediastinum and was performed without procedural complications.”

Although EUS-FNA “has emerged ... as a valuable tool for mediastinal lymph node staging in lung cancer” during the past decade, it is best suited for sampling lymph nodes in the posterior mediastinum, the researchers pointed out. This method is performed via the esophagus, as ultrasonographic imaging does not penetrate air-filled structures. Therefore, “the region immediately anterior to the trachea is a ‘blind spot’ for EUS-FNA.” The primary reason for false-negative samples with EUS-FNA appears to be lymph node metastases that are located in sites inaccessible to EUS-FNA. Since EBUS-FNA does not have EUS-FNA’s blind spot, anterior mediastinal lymph nodes can be visualized with this procedure. In this way, EBUS-FNA complements the mediastinal access of EUS-FNA, they explained.

MORE ACCURATE THAN MEDIASTINOSCOPY?

“Patients with suspicious lung tumors in the absence of mediastinal adenopathy on CT and PET, particularly those with centrally located tumors or intraparenchymal lymphadenopathy, have traditionally undergone mediastinal staging using mediastinoscopy followed by surgical exploration,” the investigators stated. “Our findings suggest that EUS plus EBUS may be a substitute for mediastinoscopy in most cases.”

Mediastinoscopy, which is performed under general anesthesia, has a negative predictive value of 89% and a positive predictive value of 100%. An average sensitivity of approximately 78% has been shown for the detection of mediastinal lymph node metastases in cervical mediastinoscopy studies, Dr. Wallace told Pulmonary Reviews. However, the procedure is not without limitations.

“Mediastinoscopy is best suited for sampling lymph nodes in the pretracheal and paratracheal regions,” the investigators stated. “Although generally safe, mediastinoscopy has a 2% risk of major morbidity and a 0.08% risk of mortality and is substantially more costly than EUS-FNA.... In our study, the negative predictive value of EUS plus EBUS was estimated to be 97%, approaching that of [the diagnostic standard] thoracotomy with mediastinal lymph node dissection.”

While the study did not directly compare EUS plus EBUS with mediastinoscopy and other surgical techniques, “it is certainly possible that EUS plus EBUS is more accurate” than mediastinoscopy, in addition to being clearly less invasive, Dr. Wallace said. “Mediastinoscopy is only able to access the lymph nodes in the anterior mediastinum, similar to those accessible by EBUS-FNA. Lymph nodes, particularly in the aortopulmonary window, and the lower mediastinum are not accessible to standard mediastinoscopy, although some can be sampled by an additional surgical procedure.”

If mediastinoscopy had been performed only when results from EUS plus EBUS were negative, the surgical procedure would have been avoided in 28% of the 138 patients in the study, the researchers stated. If EUS plus EBUS had been used to completely replace mediastinoscopy, 97% would have been correctly labeled as negative.

Additional avenues of research remain for the role that EUS plus EBUS may play in the staging of suspected lung cancer. “There are many other new questions that will be explored by our group and others, such as the accuracy of EUS plus EBUS to restage lung cancer after chemoradiotherapy, the ‘learning curve’ for EBUS, and the cost-effectiveness of EUS plus EBUS versus surgical staging,” Dr. Wallace said.           

—John Merriman

Suggested Reading
Detterbeck FC, Jantz MA, Wallace M, et al. Invasive mediastinal staging of lung cancer: ACCP evidence-based clinical practice guidelines (2nd edition). Chest. 2007;132(3 Suppl):202S-220S.
Wallace MB, Pascual JMS, Raimondo M, et al. Minimally invasive endoscopic staging of suspected lung cancer. JAMA. 2008;299(5):540-546.

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