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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.

Several techniques are available for the diagnosis of suspected lung cancer, including standard flexible bronchoscopy, transthoracic needle aspiration, and sputum cytology. Mediastinal staging of lung cancer is essential for treatment planning and assessment of prognosis, and has traditionally been performed surgically. Although cervical mediastinoscopy is regarded as the “gold standard” for sampling mediastinal lymph nodes, this procedure typically requires hospitalization and general anesthesia.1 Current endobronchial ultrasound (EBUS) techniques provide less invasive lung cancer diagnosis and staging. Recent research has examined the application of endobronchial ultrasound-based assessment for initial diagnosis of lung cancer, mediastinal staging and restaging after neoadjuvant therapy, and evaluation of tumor genetic markers.

BRONCHOSCOPIC LUNG CANCER DIAGNOSIS

Evidence-based clinical guidelines for the diagnosis of lung cancer developed by the American College of Chest Physicians reviewed the sensitivity of standard bronchoscopy (ie, without EBUS or electromagnetic navigation) and ancillary procedures that are often performed in combination with flexible bronchoscopy, such as endobronchial biopsy, brushing, washing, and standard transbronchial needle aspiration (TBNA).2 A comprehensive review of published studies from 1971 to 2004 was included in the analysis. Overall, the sensitivity of standard flexible bronchoscopy was 88% (67% to 97%) for the diagnosis of central bronchogenic carcinoma and 78% (36% to 88%) for the diagnosis of peripheral bronchogenic carcinoma. Newer techniques have been developed that appear to provide more consistent diagnosis of primary lesions.

Electromagnetic navigation bronchoscopy (ENB) is a functional tool in biopsy planning that uses computed tomography (CT) mapping to precisely locate peripheral lesions. After real-time navigation to the peripheral lesion with a steerable probe, tissue collection may be optimized by guiding sampling instruments directly to the lesion through an extendable working channel.3 A prospective pilot study examined the feasibility and safety of ENB to reach peripheral lesions and lymph nodes in patients with suspected lung cancer lesions or enlarged mediastinal lymph nodes.3 Diagnostic tissue was obtained in 80.3% of attempts, including 74% of procedures involving peripheral lung lesions and 100% of procedures involving lymph nodes.

IMPROVING DIAGNOSIS WITH ULTRASOUND

Another diagnostic method is EBUS, which uses reflected sound waves to better visualize lesions at the time of biopsy.4 Radial probe endobronchial ultrasound (RP-EBUS) employs a rotating ultrasound transducer at the end of a probe, and is used either with or without a water-filled balloon to improve ultrasound transduction and image quality. Convex-probe ultrasound uses a curvilinear ultrasound probe at the end of a bronchoscope, which allows for real-time TBNA visualization.4 A recent meta-analysis examined the yield of RP-EBUS for the evaluation of peripheral pulmonary lesions in 16 studies with a combined population of 1,420 patients.5 The overall sensitivity of RP-EBUS for the detection of lung cancer was 73%, and the specificity was 100%. In a prospective, randomized clinical trial of patients with peripheral lung lesions, the combination of ENB and RP-EBUS produced a diagnostic yield of 88%, compared with 69% with RP-EBUS alone and 59% with ENB alone (P = .02).6 Although this finding suggests that a multimodal approach combining ENB and RP-EBUS may improve lung cancer diagnosis, the sample size was relatively small (118 patients).

ENDOBRONCHIAL ULTRASOUND FOR LUNG CANCER STAGING

Reproduced with permission from the American College of Chest Physicians (Yasufuku K, et al. Comparison of endobronchial ultrasound, positron emission tomography, and CT for lymph node staging of lung cancer. Chest 2006; 130:10–18).
Figure 1. The diagnostic reach of various ultrasound sampling techniques is shown with 1, highest mediastinal; 2, upper paratracheal; 4, lower paratracheal; 5, subaortic; , subcarinal; 8, paraesophageal; 9, pulmonary ligament; 10, hilar; 11, interlobar; and 12, lobar. Endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) is performed via the airway as opposed to endo-scopic ultrasound with fine-needle aspiration (EUS-FNA), which is carried out in the esophagus.7
A promising application for EBUS is its use as a less invasive method for confirming metastatic mediastinal lymph nodes in the staging of lung cancer. Figure 1 shows the distribution of the mediastinal lymph nodes and the various diagnostic techniques that may be used to sample different lymph node stations.7

In a prospective study of potentially operable patients from Japan with proven (n = 96) or suspected (n = 6) lung cancer, investigators compared CT, positron emission tomography (PET), and EBUS-TBNA for mediastinal lymph node staging using surgical histology as the reference standard.7 The accuracy of staging was significantly greater with EBUS-TBNA (98%) than either PET (72.5%) or CT (60.8%) (P < .00001).

A recent retrospective study examined the use of EBUS-TBNA for clarification of 127 PET-positive hilar or mediastinal lymph nodes from 109 patients with suspected lung cancer.1 In 77 patients (71%), EBUS-TBNA successfully identified cancerous lymph nodes and obviated the need for further surgical biopsy. In 96 patients with definitive reference pathology, the sensitivity of EBUS-TBNA was 91%, specificity was 100%, and diagnostic accuracy was 92%. The positive predictive value of EBUS was 100%, but the negative predictive value (ie, the proportion of patients with negative EBUS-TBNA who were also negative on surgical pathology) was only 60%. This suggests a relatively high rate of false-negative EBUS-TBNA findings in this PET-positive group of patients.

Another recent study prospectively evaluated the usefulness of EBUS-TBNA after PET-CT for mediastinal staging in 117 patients with potentially operable non–small cell lung cancer (NSCLC).8 Patients were classified as either N2- or N3-positive or -negative using EBUS-TBNA, and patients who were N2- or N3-negative underwent surgical staging with lymph node dissection. Mediastinal node metastasis was confirmed by EBUS-TBNA in 37 nodal stations of 27 patients. Ninety patients who were negative by EBUS-TBNA underwent surgery with lymph node dissection. Three were reclassified as positive and 87 as negative. The overall sensitivity of EBUS-TBNA for the detection of mediastinal metastases was 90% versus 70% with PET-CT (P = .052). For the subgroup of 61 patients who had a normal mediastinum by PET-CT, nine were found to have mediastinal metastases at surgical evaluation. Six of these nine false-negatives were correctly identified by EBUS-TBNA.

Similar results were found in a study examining the use of EBUS-TBNA in 97 patients with confirmed NSCLC, no enlarged lymph nodes on CT (ie, no lymph nodes larger than 1 cm in short axis), and no abnormal mediastinal PET findings.9 Lymph nodes as small as 5 mm by ultrasound imaging at stations 2R, 2L, 4R, 4L, 7, 10R, 10L, 11R, and 11L were aspirated, and all patients underwent surgical staging. Malignant lymph nodes were detected by surgical staging in nine patients, and eight of these were identified by EBUS-TBNA. The sensitivity of EBUS-TBNA for the detection of mediastinal metastases was 89%; the specificity was 100%; and the negative predictive value was 99%.

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