ga

Skip to content

My Files [0]

These are the files you have added to your collection.

  • You don't have any documents yet, feel free to browse the website and add documents.

CADTH » Search All Products » CADTH Technology Overviews » Volume 1 - Issue 2 » Endobronchial Ultrasound for Lung Cancer Diagnosis and Staging: A Review of the Clinical and Cost-Effectiveness

Endobronchial Ultrasound for Lung Cancer Diagnosis and Staging: A Review of the Clinical and Cost-Effectiveness

From CADTH Technology Overviews, Volume 1, Issue 2, June 2010

[Adapted from Ho C, Clark M, Argáez C. Endobronchial ultrasound for lung cancer diagnosis and staging: a review of the clinical and cost-effectiveness. (Health Technology Inquiry Service). Ottawa: Canadian Agency for Drugs and Technologies in Health; 2009.]

Introduction

Despite advances in treatment, lung cancer is the leading cause of death from malignancies in Canada and worldwide.1 Diagnosis and staging of lung cancer are needed to start early treatment, determine the prognosis, and to decide the appropriate treatment plan.2-4 The presence or absence of metastatic disease in the mediastinal lymph nodes is determined during staging.2-4 Mediastinal staging can be non-invasive or invasive. Non-invasive staging can be done using computed tomography (CT), positron emission tomography (PET), and PET-CT.4-6 Invasive staging, which provides a definitive tissue diagnosis, involves the use of surgical biopsy (mediastinoscopy) or needle biopsy, such as transesophageal ultrasound (EUS), endobronchial ultrasound (EBUS), conventional transbronchial needle aspiration (TBNA), CT fluoroscopy-guided TBNA, EUS-guided fine needle aspiration (EUS-FNA), CT-guided transthoracic needle aspiration (CTTTNA), electromagnetic guidance bronchoscopy-TBNA, and EBUS-guided TBNA (EBUS-TBNA).5,6

EBUS is a new technology that involves the introduction of an ultrasound probe into the thoracic region through the bronchial airway while patients are under conscious sedation or general anesthesia.7 The probe is used to generate images of pulmonary and mediastinal structures. Its use allows for the minimally invasive sampling of peripheral pulmonary lesions, and mediastinal and hilar lesions.8,9 The development of the built-in linear probe, as opposed to a radial probe, enables real-time guidance during EBUS-TBNA.10,11

Because of its recent introduction and its increased use in clinical practice, a review of the clinical effectiveness and cost-effectiveness of EBUS for the diagnosis and staging of lung cancer is needed.

Objective

The objective of the report is to answer the following research questions:

  • What is the clinical effectiveness of endobronchial ultrasound (EBUS) for the diagnosis and staging of lung cancer?
  • What is the cost-effectiveness of EBUS for the diagnosis and staging of lung cancer?

Methods

The following bibliographic databases were searched through the Ovid interface: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, and Embase. Parallel searches were run in PubMed and The Cochrane Library (Issue 1, 2009). The search strategy comprised controlled vocabulary, such as the National Library of Medicine’s MeSH (Medical Subject Headings), and keywords. No filters were applied to limit the retrieval by study type.

The search was restricted to English language articles that were published between 2004 and April 2009. Regular alerts were established on Embase and MEDLINE, and information that was retrieved through alerts was current to May 2009.

Grey literature was identified by searching the websites of health technology assessment (HTA) and related agencies, professional associations, and other specialized databases. Google and other Internet search engines were used to search for additional information. These searches were supplemented by handsearching the bibliographies and abstracts of key papers, and through contacts with appropriate experts and agencies.

The quality of the HTA and meta-analysis were assessed using the Oxman and Guyatt criteria for the quality of systematic reviews.12 Economic study quality was assessed using Drummond’s quality checklist.13

Results

One HTA, one meta-analysis, two cost analyses, and three observational studies were identified regarding the use of EBUS for lung cancer diagnosis and staging.

 

Clinical

A 2009 meta-analysis assessed the overall diagnostic accuracy of EBUS-TBNA in detecting metastatic mediastinal lymph nodes in lung cancer.14 The meta-analysis included 11 prospective studies that enrolled a total of 1,299 patients, ranging in age from 58 years old to 69 years old and who were suspected of having lung cancer. Eight studies enrolled patients who were selected on the basis of positive CT or PET results, and the remaining three studies enrolled patients regardless of CT or PET results. Among the patients who had positive CT or PET results of suspected lymph node metastasis, the sensitivity of EBUS-TBNA was higher compared with those who did not have positive CT or PET results. EBUS-TBNA had a pooled sensitivity of 0.93 and a pooled specificity of 1.00 for lung cancer detection and staging. Complications occurred in two patients. One patient experienced a major pneumothorax and required chest tube drainage after the EBUS-TBNA procedure, and one patient experienced minor hypoxemia during the procedure (this complication is not EBUS-specific). The meta-analysis received a high-quality score when it was assessed, based on Oxman and Guyatt’s criteria for scientific quality.12

Two of the studies that were included in the meta-analysis compared EBUS-TBNA with conventional TBNA15 and with mediastinoscopy.16 EBUS-TBNA was found to be more sensitive than conventional TBNA. It detected 69% compared with 36% of malignant lymph nodes in 138 patients who had lung or mediastinal abnormality on CT. In another population of 66 patients who were clinically suspected of having non-small cell lung cancer (NSCLC), EBUS-TBNA detected 91% of malignancies compared with 78% with mediastinoscopy. Three prospective trials looked at the diagnostic accuracy of EBUS-TBNA in a total of 500 patients who were suspected of having lung cancer.17-19  The findings from these prospective studies correspond with the conclusion of the meta-analysis. The sensitivities of mediastinal lymph node staging range from 85% to 90%, with specificities of 100%.

A 2008 HTA focused on the effectiveness and safety of EBUS in the detection and staging of lung cancer in patients with established or suspected lung cancer.20 The HTA found that EBUS-TBNA statistically significantly increased the diagnostic yield for mediastinal lymph nodes compared with conventional TBNA, particularly for locations other than subcarinal lymph nodes.

Economic

A cost-effectiveness analysis published in 2008 examined whether or not the introduction of EBUS-guided procedures for the investigation of NSCLC, mediastinal and hilar masses, endobronchial cancer, and peripheral lung lesions represented value for money in the Australian health care system.21 The cost analysis indicated that the cost of EBUS-TBNA was A$1,120 per procedure (C$996), which translated to a savings of A$347 per patient (C$308) compared with conventional TBNA for NSCLC staging or diagnosis of mediastinal and hilar masses. This reflects the economic benefits that are associated with the improved yield resulting from the use of EBUS-guided procedures. This cost analysis was considered to be rigourous, based on Drummond's quality checklist for economic studies.13

A cost study also found that a combined approach of TBNA, EBUS-TBNA, and mediastinoscopy is the most cost-effective for mediastinal lymph node staging in NSCLC, compared with TBNA alone, EBUS-TBNA, or mediastinoscopy.22

According to the Australian cost analysis, the estimated number of patients who are eligible per year to undergo pathological assessment for NSCLC staging and diagnosis of mediastinal masses ranges from 1,456 to 2,262 (15% to 23%) among a total of 9,611 patients with lung cancer. Based on Canadian Cancer Statistics,1 the number of new cases of lung cancer in Canada in 2009 is estimated to be 23,400. Assuming that the figures in Australia apply to Canada and that the procedural costs in the two countries are similar, between 3,510 and 5,382 Canadian patients could undergo EBUS-TBNA per year, with total costs ranging from an estimated C$3,496,000 to an estimated C$5,360,000 per year. The use of EBUS-TBNA instead of conventional TBNA would provide an annual cost savings of C$839,000 to C$1,286,400.

Limitations

The HTA that was included did not include a meta-analysis, and the conclusions of the report were based on an assessment of the findings from the individual trials. Based on Oxman and Guyatt’s assessment tool for scientific quality,12 this HTA was not considered to be of high quality. There were no methods to combine the findings of the relevant studies, and the conclusions were partially supported by the data.

Conclusions

Given the existing evidence, EBUS is an accurate and safe tool to use in lung cancer diagnosis and staging. The cost-effectiveness of EBUS has not been evaluated, but cost-analyses show that EBUS-TBNA reduced the staging cost by 24% per patient. Using Australian cost-analysis data, and assuming that the costs are similar in Canada, the use of EBUS-TBNA compared with the use of conventional TBNA in Canada for NSCLC staging and the diagnosis of mediastinal masses could lead to estimated savings of C$0.8 million to C$1.3 million per year in the Canadian health care system. The limitation of this cost analysis is that conventional TBNA is not the standard of care for mediastinal staging. There are minimal data on the comparison of EBUS with mediastinoscopy.

References

  1. Canadian Cancer Society's Steering Committee. Canadian cancer statistics 2009 [Internet]. Toronto: Canadian Cancer Society; 2009. [cited 2010 May 3]. Available from: http://www.cancer.ca/canada-wide/about%20cancer/cancer%20statistics/~/media/CCS/Canada%20wide/Files%20List/English%20files%20heading/pdf%20not%20in%20publications%20section/Stats%202009E%20Cdn%20Cancer.ashx
  2. Midthun DE. Overview of the initial evaluation, treatment and prognosis of lung cancer. 2008 May 14 [cited 2008 Sep 22]. In: UpToDate [Internet]. Version 16.2. Waltham (MA): UpToDate; c 2005 - . Available from: www.uptodate.com Subscription required.
  3. NCCN clinical practice guidelines in oncology: non-small cell lung cancer. Fort Washington (PA): National Comprehensive Cancer Network; 2009.
  4. Yasufuku K, Fujisawa T. Staging and diagnosis of non-small cell lung cancer: invasive modalities. Respirology. 2007;12(2):173-83.
  5. Yasufuku K, Nakajima T, Fujiwara T, Chiyo M, Iyoda A, Yoshida S, et al. Role of endobronchial ultrasound-guided transbronchial needle aspiration in the management of lung cancer. Gen Thorac Cardiovasc Surg. 2008;56(6):268-76.
  6. Schipper P, Schoolfield M. Minimally invasive staging of N2 disease: endobronchial ultrasound/transesophageal endoscopic ultrasound, mediastinoscopy, and thoracoscopy. Thorac Surg Clin. 2008;18(4):363-78.
  7. Yasufuku K, Nakajima T, Chiyo M, Sekine Y, Shibuya K, Fujisawa T. Endobronchial ultrasonography: current status and future directions. J Thorac Oncol. 2007;2(10):970-9.
  8. Sheski FD, Mathur PN. Endobronchial ultrasound. Chest [Internet]. 2008 Jan [cited 2009 Apr 28];133(1):264-70. Available from: http://www.chestjournal.org/content/133/1/264.full.pdf+html?sid=e21fbfaf-3b7f-4b00-b589-9c58db813ad2
  9. El-Bayoumi E, Silvestri GA. Bronchoscopy for the diagnosis and staging of lung cancer. Semin Respir Crit Care Med. 2008;29(3):261-70.
  10. Gomez M, Silvestri GA. Endobronchial ultrasound for the diagnosis and staging of lung cancer. Proc Am Thoracic Soc. 2009 Apr;6(2):180-6.
  11. Steinfort DP, Wurzel D, Irving LB, Ranganathan SC. Endobronchial ultrasound in pediatric pulmonology. Pediatr Pulmonol. 2009 Apr;44(4):303-8.
  12. Oxman AD, Guyatt GH. Validation of an index of the quality of review articles. J Clin Epidemiol. 1991;44(11):1271-8.
  13. Drummond MF, Sculpher MJ, Torrance GW, O'Brien BJ, Stoddart GL. Methods for the economic evaluation of health care programmes. 3rd ed. Oxford (UK): Oxford University; 2005. (Oxford medical publications).
  14. 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 May;45(8):1389-96.
  15. Wallace MB, Pascual JMS, Raimondo M, Woodward TA, McComb BL, Crook JE, et al. Minimally invasive endoscopic staging of suspected lung cancer. JAMA [Internet]. 2008 [cited 2009 Apr 27];299(5):540-6. Available from: http://jama.ama-assn.org/cgi/reprint/299/5/540
  16. Ernst A, Anantham D, Eberhardt R, Krasnik M, Herth FJF. Diagnosis of mediastinal adenopathy-real-time endobronchial ultrasound guided needle aspiration versus mediastinoscopy. J Thorac Oncol. 2008;3(6):577-82.
  17. Szlubowski A, Kuzdzal J, Kolodziej M, Soja J, Pankowski J, Obrochta A, et al. Endobronchial ultrasound-guided needle aspiration in the non-small cell lung cancer staging. Eur J Cardiothorac Surg. 2009;35(2):332-6.
  18. Hwangbo B, Kim SK, Lee HS, Lee HS, Kim MS, Lee JM, et al. Application of endobronchial ultrasound-guided transbronchial needle aspiration following integrated positron emission tomography/CT in mediastinal staging of potentially operable non-small cell lung cancer. Chest. 2008 Dec 31;135(5):1280-7.
  19. Omark PH, Eckardt J, Hakami A, Olsen KE, Jorgensen OD. The value of mediastinal staging with endobronchial ultrasound-guided transbronchial needle aspiration in patients with lung cancer. Eur J Cardiothorac Surg. 2009 Sep;36(3):465-8.
  20. Sabirin J, Mohd Tahir N. Endobronchial ultrasound (EBUS) [Internet]. Malaysia: Health Technology Assessment Unit, Ministry of Health Malaysia; 2008. [cited 2009 Apr 21]. Available from: http://www.inahta.org/Publications/Briefs-Checklist-Impact/2008/3815/
  21. Endobronchial ultrasound-guided procedures [Internet]. Canberra, Australia: Department of Health and Ageing, Commonwealth of Australia; 2008. [cited 2009 Jul 14]. (MSAC application 1108). Available from: http://www.health.gov.au/internet/msac/publishing.nsf/Content/115CC907F00447B3CA2575AD0082FD6C/$File/1108report.pdf
  22. Kunst PWA, Eberhardt R, Herth FJF. Combined EBUS real time TBNA and conventional TBNA are the most cost-effective means of lymph node staging. J Bronchology. 2008;15(1):17-20.