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Bronchoscopy and endobronchial ultrasound for diagnosis and staging of lung cancer

May 1, 2012|Cleveland Clinic Journal of Medicine
Francisco Aécio Almedia, MD, MS, FCCP
Author and Disclosure Information

Francisco Aécio Almedia, MD, MS, FCCP
Associate Staff Member, Director, Interventional Pulmonary Medicine Fellowship Program, Respiratory Institute, Cleveland Clinic, Cleveland, OH

Correspondence: Francisco Aécio Almeida, MD, MS, FCCP, Critical Care Medicine, Cleveland Clinic, 9500 Euclid Avenue, A90, Cleveland, OH 44195; almeidf@ccf.org

Dr. Almeida reported that he has no financial relationships that pose a potential conflict of interest with this article.

This article was developed from an audio transcript of Dr. Almeida’s presentation at the “Advances in Lung Cancer Evaluation and Management” symposium held in Cleveland, Ohio, on April 30, 2011. The transcript was formatted and edited by Cleveland Clinic Journal of Medicine staff for clarity and consciseness and was then reviewed, revised, and approved by Dr. Almeida.

ABSTRACTVarious techniques, including standard bronchoscopy, transthoracic needle aspiration and mediastinoscopy, are used for diagnosis and staging of lung cancer. Minimizing the number of invasive procedures for lung cancer diagnosis and staging is preferred, however, and a growing number of bronchoscopic techniques are being used. Currently available techniques for the initial diagnosis of lung cancer include electromagnetic navigation bronchoscopy with computed tomography mapping and sample collection, endobronchial ultrasound (EBUS) using radial or convex probe tips, and the combination of the two approaches. EBUS with transbronchial needle aspiration (EBUS-TBNA) is highly specific and sensitive for the examination of mediastinal lymph nodes. Several studies have demonstrated the utility of this approach for less invasive lung cancer mediastinal staging. EBUS-TBNA has also been used in the collection of tissue samples for the analysis of tumor biomarkers that significantly influence the selection of cancer treatment strategies. Evidence suggests that EBUS-TBNA may be less useful for restaging patients with lung cancer after cytotoxic therapy.

Guided fine-needle aspiration with ultrasound bronchoscopy

An additional approach to mediastinal lung cancer staging is endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA) and EBUS-TBNA in a single procedure. The use of EBUS-TBNA and EUS-B-FNA for NSCLC staging was examined in a prospective study of 150 patients with confirmed or strongly suspected NSCLC.10 Patients underwent EBUS-TBNA, and EUS-B-FNA then was used for nodes that were inaccessible through the airways. EBUS-TBNA diagnosed mediastinal metastases in 38 of 143 patients, and three more patients were identified by additional EUS-B-FNA. Surgery identified four additional patients with mediastinal metastases that were negative by both EBUS-TBNA and EUS-B-FNA. Overall sensitivity for the detection of mediastinal metastases was 84.4% with EBUS-TBNA alone versus 91.1% with EBUS-TBNA followed by EUS-B-FNA, but this was not statistically significant (P = .332).

A second study of 139 patients with confirmed NSCLC reported similar results when EBUS-TBNA and EUS-B-FNA were performed using a single ultrasound bronchoscope.11 The sensitivity for detection of mediastinal metastases was 89% with EUS-FNA, 92% with EBUS-TBNA, and 96% with the combined approach. The specificity was 100% for all three approaches. The negative predictive values were 82% for the esophageal approach, 92% for the endobronchial approach, and 86% for the combined approach.

Meta-analyses support EBUS-TBNA for staging

The usefulness of EBUS-TBNA for NSCLC staging has been examined in two recent meta-analyses. The first included data from 11 studies of EBUS-TBNA with 1,299 patients.12 Overall, the included studies yielded a pooled sensitivity of 93% and a specificity of 100% for the detection of metastatic mediastinal lymph nodes (95% CI). The sensitivity was higher for patients who were selected for evaluation on the basis of positive PET or CT findings than for patients without selection by PET or CT (0.94 vs 0.76) (P < .05). The authors concluded that EBUS-TBNA for lung cancer staging is accurate, safe, and cost-effective, and that selection of patients based on CT or PET findings resulted in higher sensitivity.

The second meta-analysis examined data from 10 studies evaluating the utility of EBUS-TBNA for lung cancer staging.13 This meta-analysis also yielded high sensitivity (88%) and specificity (100%) of EBUS-TBNA for the identification of metastatic mediastinal lymph nodes.

EVALUATION OF EBUS VERSUS MEDIASTINOSCOPY AND OTHER INVASIVE TESTS

Although several studies suggest that EBUS-TBNA provides an accurate and less invasive method for assessment of mediastinal lymph nodes in the mediastinal staging of patients with NSCLC, few studies have directly compared EBUS-TBNA with mediastinoscopy. In a prospective crossover trial, 66 patients with suspected NSCLC underwent mediastinal staging using EBUS-TBNA followed by mediastinoscopy, with surgical lymph node dissection as the reference standard.14 The overall diagnostic yield for all lymph nodes was significantly higher with EBUS-TBNA than with mediastinoscopy (91% vs 78%) (P = .007). However, this difference was primarily due to a higher success rate in the diagnosis of subcarinal lymph nodes (98% vs 78%) (P = .007), which can be difficult to evaluate with mediastinoscopy. Differences between the two methods at other node stations were not statistically significant (Table). In the 57 patients who were diagnosed with NSCLC, the prediction of the correct pathologic stage did not differ significantly between the two approaches (93% with EBUS-TBNA vs 82% with mediastinoscopy) (P = .083).

A more recent randomized, multicenter clinical trial compared endosonographical staging (EUS-FNA and EBUS-TBNA) with mediastinoscopy in 241 patients with resectable suspected NSCLC.15 Patients were randomized to either surgical staging or to endosonography followed by surgical staging for those without nodal metastases using ultrasound-guided FNA. The sensitivity for detection of nodal metastases was 79% with surgical staging and 94% with endosonography and surgical staging (P = .02). Comparing the sensitivity of the two procedures alone, without follow-up surgical staging when ultrasound was negative, the sensitivities of the two approaches were similar: 79% with mediastinoscopy and 85% with endosonographic staging alone.

Another retrospective study examined the results of EBUS-TBNA for the initial diagnosis and staging of 88 patients with known or suspected lung cancer who underwent at least one invasive diagnostic or staging procedure before EBUS-TBNA.16 The selection of EBUS-TBNA and bronchoscopy as the initial test for diagnosis and staging could have prevented at least one invasive test in 50% of patients, and could have been the only invasive test procedure in 47.7% of individuals. In 27 patients who underwent two or more invasive tests, EBUS-TBNA could have avoided at least one invasive test in 16 patients (59%).

PATHWAYS TO DIAGNOSIS

Reprinted with permission from Current Opinion in Pulmonary Medicine (Almeida FA, et al. Initial evaluation of the nonsmall cell lung cancer patient: diagnosis and staging. Curr Opin Pulm Med 2010; 16:307–314).
Figure 2. This diagnostic algorithm should be followed for patients with suspected non–small cell lung cancer (NSCLC).17 CBC = complete blood count; COPD = chronic obstructive pulmonary disease; CT = computed tomography; Dlco = diffusion capacity of the lung for carbon monoxide; EBUS-TBNA = endobronchial ultrasound-guided trans-bronchial needle aspiration; PET = positron emission tomography
A proposed diagnostic algorithm for suspected NSCLC is shown in Figure 2.17 When lung cancer is highly suspected on the basis of focused patient history and physical examination, the patient should undergo CT-PET or chest CT with contrast that also should assess the liver and adrenal glands. If the patient has radiographic evidence of metastatic disease, the next step is biopsy of the most accessible, most advanced lesion for tissue diagnosis and staging. In patients without evidence of metastatic disease, the next step is to evaluate the mediastinal lymph nodes. Patients with evidence of nodal involvement on PET-CT or without evidence of nodal involvement but with larger tumors (eg, stage T1b or larger) may be evaluated using EBUS-TBNA as the first invasive test if available or mediastinoscopy. Standard bronchoscopy in conjunction with EBUS-TBNA has the capability of sampling the primary lesion when the mediastinal staging fails to demonstrate malignant disease. Therefore, it can provide a definitive diagnosis in addition to mediastinal staging during one single procedure, whereas mediastinoscopy typically cannot assess the primary lesion if necessary.

APPLICATIONS IN MOLECULAR TUMOR PROFILING

Genetic profiling of lung cancer tissue samples is essential to identify biomarkers that significantly influence treatment responses, and EBUS-TBNA has been used to obtain biopsy tissue samples for genetic analysis. One study examined the detection of EGFR gene mutations in biopsy tissue samples obtained from 46 patients with metastatic adenocarcinoma to the hilar or mediastinal lymph nodes diagnosed by EBUS-TBNA.18 Recut sections of the paraffin-embedded samples yielded tumor cells in 43 patients, and tissue samples were examined for mutations of EGFR exons 19 and 21. Five patients underwent surgical resection, and three of these yielded samples with EGFR mutations at exon 21. Examination of the 43 EBUS-TBNA specimens revealed EGFR mutations in 11. These included three of the mutations that were identified from surgical specimens. A more recent study examined the concordance between mutations of KRAS, EGFR, BRAF, and PIK3CA obtained by EBUS-TBNA, EUS-B-FNA, and histologic samples obtained during surgical staging from 43 patients.19KRAS mutations were identified in six patients, EGFR mutation in one patient, and PIK3CA mutation in one patient. The investigators observed 100% concordance between cytologic fine-needle aspirates and histologic specimens, suggesting no additional benefit of more invasive procedures for the evaluation of tumor biomarkers.

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