CRD summary

The review assessed the sensitivity and specificity of endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) biopsy for mediastinal lymph node staging in patients with lung cancer. The authors concluded that EBUS-TBNA biopsy had excellent overall test performance and specificity. The sensitivities reported by included studies varied widely (minimum reported value 0.33), so these conclusions should be viewed with caution.

Authors' objectives

To determine the sensitivity and specificity of endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) biopsy for mediastinal lymph node staging in patients with lung cancer, and to compare these with published results for computed tomography (CT) and positron emission tomography (PET) scans.

Searching

MEDLINE, EMBASE and the Cochrane Library were searched from inception to February 2008. Search terms were reported (full search strategy published in an on-line appendix, see URL for Additional Data). On-line trial registers abstracts from major scientific meetings (2005 to 2007) were also searched to identify unpublished studies. Bibliographies of all included articles were screened for additional studies. No language restrictions were applied.

Study selection

Studies that assessed endobronchial ultrasound (EBUS) for mediastinal staging in patients with suspected or confirmed lung cancer (both small and non-small cell subtypes) were eligible for inclusion. Studies that included patients with primary underlying disease other than lung cancer, studies that focused on mediastinal node staging alone and studies of re-staging after induction therapy were excluded.

The inclusion criteria used by studies in the review varied and, where reported, included CT mediastinal lymph nodes less than 1cm and over 1cm on short axis, PET positive mediastinal nodes, operable disease, and stage I to IIIa. Where reported, the reference standard was mediastinoscopy and/or thoracotomy.

Three reviewers independently assessed studies for inclusion and disagreements were resolved by consensus.

Assessment of study quality

The methodological quality of included studies was assessed using the 14-item QUADAS (Quality Assessment of Diagnostic Accuracy Studies) tool, including items relating to: reporting quality; participant selection and spectrum; appropriateness of the reference standard; verification biases; blinding; disease progression bias; and handling of withdrawals and indeterminate results.

The authors did not state how many reviewers performed the quality assessment.

Data extraction

Data were extracted to populate 2x2 contingency tables of test performance (absolute numbers of true positive, false negative, false positive and true negative results). Data were extracted with the patient as the unit of analysis to prevent cluster sampling error and to focus on the ability of EBUS-TBNA to accurately stage the mediastinum as a whole. Sensitivity and specificity, with 95% confidence intervals (CIs) were calculated for each study.

The authors did not state how data were extracted for the review, or how many reviewers performed the data extraction.

Methods of synthesis

Pooled estimates of sensitivity and specificity and a summary Receiver Operating Characteristic (sROC) curve were generated using a bivariate mixed-effects regression model (Midas9 module in Stata 9.2). Likelihood ratios were calculated from pooled estimates of sensitivity and specificity. Between study heterogeneity was assessed using the I² test.

Results of the review

Ten studies (six full papers and four published abstracts), with a total of 782 participants (range 16 to 300), were included in the review. The mean quality score was 6.1 (range 2 to 9) out of a possible 14 points. Methodological flaws included poor description of tests used as the reference standard, with reference standard (where reported) often varying between patients within individual studies.

The pooled estimate for the sensitivity of the endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) biopsy was 0.88 (95% CI 0.79 to 0.94), and the pooled estimate for specificity was 1.00 (95% CI 0.92 to 1.00). The corresponding estimates for positive likelihood ratio were 680.86 (95% CI 9.66 to 48000.00) and for negative likelihood ratio, 0.12 (95% CI 0.06 to 0.21).

Authors' conclusions

The authors concluded that endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) biopsy had excellent overall test performance and specificity for mediastinal lymph node staging in patients with lung cancer, and that results compare favourably with published results for computed CT and PET scans.

CRD commentary

The review addressed a clearly stated research question, with partially defined inclusion criteria; no criteria were defined for an appropriate reference standard and the reference standard used varied between studies. A variety of sources were searched for relevant studies, including potential sources of unpublished studies; no language restrictions were applied. Therefore, it is likely that a good retrieval rate of relevant studies was achieved, and the potential for language and/or publication bias was minimised. Measures were taken to avoid error and/or bias in the study selection process, but it was unclear whether similar measures were applied to data extraction and quality assessment.

The methodological quality of included studies was assessed, but not fully reported; summary quality scores, which studies have shown to be potentially misleading, were reported for included studies. Meta-analyses were conducted using an appropriate model. However, given the apparent heterogeneity in sensitivity estimates and the reference standard used across studies, the appropriateness of pooling was questionable; all but one of the included studies reported 100% specificity, which (as the authors stated) was unsurprising as the EBUS-TBNA biopsy is a tissue based test, so is similar to the reference standard.

Given the wide variation in reported sensitivities (minimum reported value 0.33), the authors' conclusion (that EBUS-TBNA has excellent overall test performance) should be viewed with caution.

Implications of the review for practice and research

Practice: The authors stated that the favourable results of endobronchial ultrasound with transbronchial needle aspiration (EBUS-TBNA) biopsy compared with both CT and PET scans does not necessarily mean that it should be adopted as the investigation of choice for staging of mediastinal lymph nodes in patients with known or suspected lung cancer; EBUS-TBNA is more invasive than imaging techniques and integrated PET/CT carries the additional advantage of screening for distant metastatic disease.

Research: The authors stated that future studies should directly compare the results of CT, PET-CT, EBUS-TBNA, mediastinoscopy and systematic lymph node dissection for staging and should better define where EBUS might fit into the diagnostic algorithm in relation to mediastinoscopy and lymph node biopsies. Studies in different institutions by different operators would greatly increase the external validity of the results of future meta-analyses on this topic.

Funding

The authors stated that their review was not commissioned.

Bibliographic details

Adams K, Shah PL, Edmonds L, Lim E. Test performance of endobronchial ultrasound and transbronchial needle aspiration biopsy for mediastinal staging in patients with lung cancer: systematic review and meta-analysis. Thorax 2009; 64(9): 757-762. [PubMed: 19454408]

Original Paper URL

http://thorax.bmj.com/content/64/9/757.abstract

Indexing Status

Subject indexing assigned by NLM

MeSH

Biopsy, Needle /methods; Bronchoscopy /methods; Endosonography /methods; Epidemiologic Methods; Humans; Lung Neoplasms /pathology /ultrasonography; Lymph Nodes /pathology /ultrasonography; Lymphatic Metastasis /pathology; Mediastinum /pathology /ultrasonography; Neoplasm Staging

AccessionNumber

12009109471

Database entry date

21/04/2010

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.