Minimally invasive methods accurately stage lung cancer

Two minimally invasive staging methods used together may be an accurate substitute for mediastinoscopy for some lung cancer patients with suspected metastatic mediastinal lymph nodes, according to a report in JAMA (299:540-546, 2008).

"Noninvasive staging with chest CT or PET is associated with high rates of false-positive and false-negative results, respectively," said Michael B. Wallace, MD, MPH, of the Mayo Clinic, Jacksonville, Florida, and his colleagues.

The lung cancer staging guidelines of the American College of Chest Physicians recommend that patients with abnormal lymph nodes on CT or PET, or centrally located tumors without mediastinal adenopathy, undergo invasive staging, with tissue confirmation of suspected metastatic mediastinal lymph nodes.

"Mediastinoscopy or thoracoscopy has been the diagnostic standard," the authors said, but less invasive methods have emerged as potential alternatives.

These new noninvasive methods include blind transbronchial needle aspiration (TBNA), endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), and, most recently, endobronchial ultrasound-guided fine-needle aspiration (EBUS-FNA).

The investigators tested the three newer methods in 138 patients with known or suspected lung cancer, based on a lung or mediastinal abnormality seen on CT, and no pathologically proven extrathoracic metastases.

Invasive staging of the mediastinum found malignant nodes in 42 (30%) of the study patients. Patients were followed for 6 months to 1 year.

TBNA, EBUS-FNA, and EUS-FNA were performed as a single combined procedure. All slides were reviewed remotely by a staff pathologist.

Samples classified as suspicious or malignant were considered positive and those that were benign or nondiagnostic were considered negative. The three procedures were completed without complications in all patients.

Sensitivity results

EBUS detected 29 of the 42 malignant lymph nodes, resulting in a significantly higher sensitivity than TBNA (69% vs 36%, P = .003), which found 15 of the malignant nodes (see Table). EUS also detected 29 malignant nodes, but EUS plus EBUS found 39 of the malignant nodes and had a higher sensitivity than any of the other noninvasive methods (93%).

TBNA had the lowest estimated negative predictive value (78%), and EUS plus EBUS had the highest (97%).

Each method had a median of one lymph node sampled. The percentage of malignant lymph nodes detected by each procedure (the number malignant/total number sampled) was 15% for TBNA, 19.7% for EBUS, and 22% for EUS.

"These findings suggest that EUS plus EBUS may allow near-complete minimally invasive mediastinal staging in patients with suspected lung cancer," the authors commented.

The results require confirmation, they said, but suggest that EUS plus EBUS may be an alternative approach for mediastinal staging in these patients.

The authors noted that "mediastinoscopy is best suited for sampling lymph nodes in the pretracheal and paratracheal regions but has limited access to the inferior and posterior mediastinum and aortopulmonary window." Further, they noted, mediastinoscopy carries a small risk of major morbidity (2%) and mortality (0.08%), and is considerably more expensive than EUS.

In this study, they said, if mediastinoscopy had been performed only when the EUS plus EBUS results were negative, the invasive procedure could have been avoided in 39 patients (28%). If EUS plus EBUS had been used in all patients without mediastinoscopy, "97% would have been correctly labeled as negative," they wrote.

Complementary tests

With EUS, the main reason for false-negative results, the researchers said, "appears to be lymph node metastases located in sites inaccessible to EUS-FNA." Thus, they said, EUS is best suited for sampling lymph nodes in the posterior mediastinum. EBUS, however, is capable of visualizing anterior mediastinal lymph nodes and thus complements the mediastinal access of EUS.

The researchers noted that the use of EUS plus EBUS testing is currently limited because of the need for training, specialized equipment, and combined expertise in endoscopy and bronchoscopy. Yet, the authors noted, the bronchoscopists who performed EBUS in their study "had only recently been trained in EBUS-FNA, and they still achieved a high level of sensitivity."