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Point/Counterpoint Editorials |

Point: Should UItrasonographic Endoscopy Be the Preferred Modality for Staging of Lung Cancer? YesEBUS for Staging Lung Cancer? Yes FREE TO VIEW

Momen M. Wahidi, MD, MBA, FCCP; Armin Ernst, MD, MHCM, FCCP
Author and Funding Information

From the Division of Pulmonary and Critical Care Medicine (Dr Wahidi) and Department of Medicine, Duke University Medical Center; and Reliant Medical Group (Dr Ernst).

Correspondence to: Momen M. Wahidi, MD, MBA, FCCP, Division of Pulmonary and Critical Care Medicine, Duke University Medical Center, Box 3683, Durham, NC 27710; e-mail: momen.wahidi@duke.edu


Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Dr Wahidi has served as a consultant with Olympus Corp and received educational grants from Olympus Corp and Pentax of America Inc. Dr Ernst has reported that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2014;145(3):447-449. doi:10.1378/chest.13-2722
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Published online

Lung cancer remains the leading cause of cancer deaths in the United States, accounting for an estimated 29% and 26% of deaths in 2012 in men and women, respectively.1 Outcomes of patients with lung cancer vary dramatically on the basis of stage, with a 5-year survival ranging from 73% for stage IA to 13% for stage IV.2 Therefore, accurate staging of lung cancer plays an essential role in patient management, dictating the optimal treatment or combination of treatments with surgery, chemotherapy, or radiation therapy. Of particular interest for precise staging is the determination of metastatic involvement in mediastinal lymph nodes. Although radiographic imaging can be helpful, it suffers from low sensitivity (chest CT scan) or low specificity (PET scan).3 Tissue sampling remains the most accurate method to make this determination, following the cliché “tissue is the issue.” Mediastinoscopy has been the standard approach to mediastinal tissue biopsy for decades, but more recently, newer ultrasonographic endoscopic technology has emerged as a sensitive and less invasive mediastinal sampling approach. This technology includes endobronchial ultrasound (EBUS) and esophageal ultrasound (EUS) used separately or in combination. In this point editorial, we argue that EBUS- and EUS-guided transbronchial needle aspiration of the mediastinum should be the preferred first approach to mediastinal staging in lung cancer over cervical mediastinoscopy (CM) because of their high sensitivity, low morbidity, and reduced cost.

A number of prospective trials have been performed with the primary goal of comparing the efficacy of CM and endoscopic ultrasonography in mediastinal staging. A study of patients with suspected non-small cell lung cancer and enlarged mediastinal lymph nodes (≥ 10 mm on chest CT scan) found EBUS-guided transbronchial needle aspiration (EBUS-TBNA) to have a higher sensitivity and negative predictive value than CM (87% and 78% vs 68% and 59%, respectively)4; this study has been criticized for selecting patients with radiographically enlarged lymph nodes (size > 1 cm). A second trial found similar results for both EBUS-TBNA and CM in sensitivity and negative predictive values (81% and 93% vs 79% and 93%, respectively) and no significant difference in determining the true pathologic N stage.5 The most robust data come from a study by Annema et al,6 which randomized patients to either CM or endosonography (EBUS-TBNA and EUS-guided fine needle aspiration) followed by CM in case no nodal metastases were found on endosonography. When lymph nodes were found to be normal by either approach, thoracotomy with lymph node dissection was performed. The study found a diagnostic sensitivity of 79% for endosonography, 85% for CM, and 94% for endosonography followed by CM and recommended the latter combined strategy as the best staging approach. In line with the findings of these studies, the American College of Chest Physicians lung cancer guidelines3 recommends ultrasound-guided needle techniques as the best first test over surgical staging in patients with a high suspicion of mediastinal involvement (grade 1B).

Although the rates of morbidity and mortality for mediastinoscopy are low (2% and 0.08%, respectively), the complications can be significant, particularly injury to vascular and mediastinal structures.3,7 On the other hand, complications from EBUS-TBNA are extremely rare. A meta-analysis of 11 studies involving 1,299 patients undergoing EBUS-TBNA revealed a complication rate of 0.15% (occurring in two patients: one with a pneumothorax and the other with self-limited hypoxemia).8 A few case reports highlighted the potential for infectious complications after EBUS-TBNA, including mediastinal abscess and mediastinitis.9-11 Only one case of death following EBUS-TBNA was reported in a patient with thrombocytopenia, prolonged coagulation tests, and renal and hepatic dysfunction; hemoptysis developed after the procedure, and the patient was not resuscitated due to family wishes.12

Several economic analyses have found EBUS alone or EBUS/EUS to be more cost-effective than mediastinoscopy in the diagnosis and staging of lung cancer.13-16 Earlier criticism of the data pointed to the lack of inclusion of the cost of mediastinoscopies performed to confirm the normal results of ultrasound-based sampling. Researchers listened and included the cost in two subsequent studies. An Australian study compared real costs derived from actual patient data at a major teaching hospital and demonstrated that EBUS-TBNA (with normal results being surgically confirmed) to be the most cost-beneficial approach (AU$2,961) compared with EBUS-TBNA alone (normal results not being surgically confirmed, AU$3,344) and mediastinoscopy (AU$8,859).16 A UK cost-effectiveness study showed that the 6-month cost of the endosonography strategy (followed by CM if results were normal) was £9,713 vs £10,459 for the surgical approach, with savings related primarily to the reduction of the number of unnecessary thoracotomies.15 In an era of ever-changing health-care delivery models and the advent of high-value care and bundled payments, these findings cannot be overlooked.

In summary, ultrasonographic endoscopy has emerged as the preferred modality for the staging of lung cancer because it is equally sensitive to mediastinoscopy yet is safer and cheaper. This statement should be qualified by emphasizing that a normal result from EBUS or EUS should not be presumed to be truly normal, and surgical sampling should ensue in these situations. Following this approach, the majority of patients with suspected lung cancer would be adequately staged, and only a handful would need mediastinoscopy. The data are robust and now endorsed by rigorously performed evidence-based societal guidelines, such as the American College of Chest Physicians lung cancer guidelines. It is time to embrace this approach and to overcome the comfort of our old ways. Learning and mastering ultrasonographic endoscopy for staging lung cancer should be part of the armamentarium of pulmonologists and thoracic surgeons who participate in the multidisciplinary care of patients with lung cancer. Our tools should conform to patient needs and not vice versa. John F. Kennedy once said, “Change is the law of life. And those who look only to the past or present are certain to miss the future.”17

ASTER

Assessment of Surgical Staging vs Endosonographic Ultrasound in Lung Cancer

CM

cervical mediastinoscopy

EBUS

endobronchial ultrasound

EBUS-TBNA

endobronchial ultrasound-guided transbronchial needle aspiration

EUS

esophageal ultrasound

NSCLC

non-small cell lung cancer

Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10-29. [CrossRef] [PubMed]
 
Shepherd FA, Crowley J, Van Houtte P, et al; International Association for the Study of Lung Cancer International Staging Committee and Participating Institutions. The International Association for the Study of Lung Cancer lung cancer staging project: proposals regarding the clinical staging of small cell lung cancer in the forthcoming (seventh) edition of the tumor, node, metastasis classification for lung cancer. J Thorac Oncol. 2007;2(12):1067-1077. [CrossRef] [PubMed]
 
Silvestri GA, Gonzalez AV, Jantz MA, et al. Methods for staging non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5_suppl):e211S-e250S. [CrossRef] [PubMed]
 
Ernst A, Anantham D, Eberhardt R, Krasnik M, Herth FJ. Diagnosis of mediastinal adenopathy-real-time endobronchial ultrasound guided needle aspiration versus mediastinoscopy. J Thorac Oncol. 2008;3(6):577-582. [CrossRef] [PubMed]
 
Yasufuku K, Pierre A, Darling G, et al. A prospective controlled trial of endobronchial ultrasound-guided transbronchial needle aspiration compared with mediastinoscopy for mediastinal lymph node staging of lung cancer. J Thorac Cardiovasc Surg. 2011;142(6):1393-1400. [CrossRef] [PubMed]
 
Annema JT, van Meerbeeck JP, Rintoul RC, et al. Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: a randomized trial. JAMA. 2010;304(20):2245-2252. [CrossRef] [PubMed]
 
Hammoud ZT, Anderson RC, Meyers BF, et al. The current role of mediastinoscopy in the evaluation of thoracic disease. J Thorac Cardiovasc Surg. 1999;118(5):894-899. [CrossRef] [PubMed]
 
Gu P, Zhao YZ, Jiang LY, Zhang W, Xin Y, Han BH. Endobronchial ultrasound-guided transbronchial needle aspiration for staging of lung cancer: a systematic review and meta-analysis. Eur J Cancer. 2009;45(8):1389-1396. [CrossRef] [PubMed]
 
Gochi F, Chen F, Aoyama A, Date H. Mediastinal infectious complication after endobronchial ultrasound-guided transbronchial needle aspiration. Interact Cardiovasc Thorac Surg. 2013;17(4):751-752. [CrossRef] [PubMed]
 
Moffatt-Bruce SD, Ross P Jr. Mediastinal abscess after endobronchial ultrasound with transbronchial needle aspiration: a case report. J Cardiothorac Surg. 2010;5:33. [CrossRef] [PubMed]
 
Parker KL, Bizekis CS, Zervos MD. Severe mediastinal infection with abscess formation after endobronchial ultrasound-guided transbrochial needle aspiration. Ann Thorac Surg. 2010;89(4):1271-1272. [CrossRef] [PubMed]
 
Miller DR, Mydin HH, Marshall AD, Devereux GS, Currie GP. Fatal haemorrhage following endobronchial ultrasound-transbronchial needle aspiration: an unfortunate first. QJM. 2013;106(3):295-296. [CrossRef] [PubMed]
 
Ang SY, Tan RW, Koh MS, Lim J. Economic analysis of endobronchial ultrasound (EBUS) as a tool in the diagnosis and staging of lung cancer in Singapore. Int J Technol Assess Health Care. 2010;26(2):170-174. [CrossRef] [PubMed]
 
Harewood GC, Pascual J, Raimondo M, et al. Economic analysis of combined endoscopic and endobronchial ultrasound in the evaluation of patients with suspected non-small cell lung cancer. Lung Cancer. 2010;67(3):366-371. [CrossRef] [PubMed]
 
Sharples LD, Jackson C, Wheaton E, et al. Clinical effectiveness and cost-effectiveness of endobronchial and endoscopic ultrasound relative to surgical staging in potentially resectable lung cancer: results from the ASTER randomised controlled trial. Health Technol Assess. 2012;16(18):1-75. [PubMed]
 
Steinfort DP, Liew D, Conron M, Hutchinson AF, Irving LB. Cost-benefit of minimally invasive staging of non-small cell lung cancer: a decision tree sensitivity analysis. J Thorac Oncol. 2010;5(10):1564-1570. [CrossRef] [PubMed]
 
Address in the Assembly Hall at the Paulskirche in Frankfurt (266). June 25, 1963. Public Papers of the President: John F. Kennedy, 1963. JFK Library website. http://www.jfklibrary.org/Research/Research-Aids/Ready-Reference/JFK-Quotations.aspx#C. Accessed August 9, 2013.
 

Figures

Tables

References

Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62(1):10-29. [CrossRef] [PubMed]
 
Shepherd FA, Crowley J, Van Houtte P, et al; International Association for the Study of Lung Cancer International Staging Committee and Participating Institutions. The International Association for the Study of Lung Cancer lung cancer staging project: proposals regarding the clinical staging of small cell lung cancer in the forthcoming (seventh) edition of the tumor, node, metastasis classification for lung cancer. J Thorac Oncol. 2007;2(12):1067-1077. [CrossRef] [PubMed]
 
Silvestri GA, Gonzalez AV, Jantz MA, et al. Methods for staging non-small cell lung cancer: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013;143(5_suppl):e211S-e250S. [CrossRef] [PubMed]
 
Ernst A, Anantham D, Eberhardt R, Krasnik M, Herth FJ. Diagnosis of mediastinal adenopathy-real-time endobronchial ultrasound guided needle aspiration versus mediastinoscopy. J Thorac Oncol. 2008;3(6):577-582. [CrossRef] [PubMed]
 
Yasufuku K, Pierre A, Darling G, et al. A prospective controlled trial of endobronchial ultrasound-guided transbronchial needle aspiration compared with mediastinoscopy for mediastinal lymph node staging of lung cancer. J Thorac Cardiovasc Surg. 2011;142(6):1393-1400. [CrossRef] [PubMed]
 
Annema JT, van Meerbeeck JP, Rintoul RC, et al. Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: a randomized trial. JAMA. 2010;304(20):2245-2252. [CrossRef] [PubMed]
 
Hammoud ZT, Anderson RC, Meyers BF, et al. The current role of mediastinoscopy in the evaluation of thoracic disease. J Thorac Cardiovasc Surg. 1999;118(5):894-899. [CrossRef] [PubMed]
 
Gu P, Zhao YZ, Jiang LY, Zhang W, Xin Y, Han BH. Endobronchial ultrasound-guided transbronchial needle aspiration for staging of lung cancer: a systematic review and meta-analysis. Eur J Cancer. 2009;45(8):1389-1396. [CrossRef] [PubMed]
 
Gochi F, Chen F, Aoyama A, Date H. Mediastinal infectious complication after endobronchial ultrasound-guided transbronchial needle aspiration. Interact Cardiovasc Thorac Surg. 2013;17(4):751-752. [CrossRef] [PubMed]
 
Moffatt-Bruce SD, Ross P Jr. Mediastinal abscess after endobronchial ultrasound with transbronchial needle aspiration: a case report. J Cardiothorac Surg. 2010;5:33. [CrossRef] [PubMed]
 
Parker KL, Bizekis CS, Zervos MD. Severe mediastinal infection with abscess formation after endobronchial ultrasound-guided transbrochial needle aspiration. Ann Thorac Surg. 2010;89(4):1271-1272. [CrossRef] [PubMed]
 
Miller DR, Mydin HH, Marshall AD, Devereux GS, Currie GP. Fatal haemorrhage following endobronchial ultrasound-transbronchial needle aspiration: an unfortunate first. QJM. 2013;106(3):295-296. [CrossRef] [PubMed]
 
Ang SY, Tan RW, Koh MS, Lim J. Economic analysis of endobronchial ultrasound (EBUS) as a tool in the diagnosis and staging of lung cancer in Singapore. Int J Technol Assess Health Care. 2010;26(2):170-174. [CrossRef] [PubMed]
 
Harewood GC, Pascual J, Raimondo M, et al. Economic analysis of combined endoscopic and endobronchial ultrasound in the evaluation of patients with suspected non-small cell lung cancer. Lung Cancer. 2010;67(3):366-371. [CrossRef] [PubMed]
 
Sharples LD, Jackson C, Wheaton E, et al. Clinical effectiveness and cost-effectiveness of endobronchial and endoscopic ultrasound relative to surgical staging in potentially resectable lung cancer: results from the ASTER randomised controlled trial. Health Technol Assess. 2012;16(18):1-75. [PubMed]
 
Steinfort DP, Liew D, Conron M, Hutchinson AF, Irving LB. Cost-benefit of minimally invasive staging of non-small cell lung cancer: a decision tree sensitivity analysis. J Thorac Oncol. 2010;5(10):1564-1570. [CrossRef] [PubMed]
 
Address in the Assembly Hall at the Paulskirche in Frankfurt (266). June 25, 1963. Public Papers of the President: John F. Kennedy, 1963. JFK Library website. http://www.jfklibrary.org/Research/Research-Aids/Ready-Reference/JFK-Quotations.aspx#C. Accessed August 9, 2013.
 
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