Original Contribution
Representativeness of Nodal Sampling With Endobronchial Ultrasonography in Non–Small-Cell Lung Cancer Staging

https://doi.org/10.1016/j.ultrasmedbio.2011.10.006Get rights and content

Abstract

The objective of our study was to determine the procedure-related requirements of mediastinal node sampling with endobronchial ultrasonography with real-time transbronchial needle aspiration (EBUS-TBNA) that would provide negative predictive value (NPV) for the identification of stage III disease in non–small-cell lung cancer (NSCLC) high enough to consider the technique equivalent to cervical mediastinoscopy. Representative EBUS-TBNA was defined as a sampling procedure obtaining satisfactory samples from normal nodes in regions 4R, 4L and 7 or diagnosing malignancy in mediastinal nodes. NPV was estimated using the results of postsurgical staging in patients who underwent surgery as a reference. Two-hundred ninety-six patients staged with EBUS-TBNA were included. Representative samples from regions 4R, 4L and 7 showing nonmalignant cytology were obtained from 98 patients (33.1%) and EBUS-TBNA detected N2/N3 disease in 150 (50.7%). Accordingly, an EBUS-TBNA procedure accomplishing the representativeness criteria required for sampling was attained in 248 of the participating patients (83.8%). The NPV of the procedure in this setting was 93.6%, with false-negative results only found in 5 patients, four of them with nodal metastasis out of the reach of EBUS-TBNA (regions 5, 8 and 9). In conclusion, representative sampling of regions 4R, 4L and 7 is achieved in more than 80% of patients staged using EBUS-TBNA, and in the procedures that attain this requirement a NPV >90% for mediastinal malignancy is reached, a figure equivalent to cervical mediastinoscopy.

Introduction

A wide range of sensitivity values have been reported for blind transbronchial needle aspiration (TBNA) when used for mediastinal lymph node sampling, with figures high enough to consider blind TBNA accurate for the management of lung cancer only when large nodes are the target (Detterbeck et al. 2007). The use of radial endobronchial ultrasonography (EBUS) before TBNA increases the sensitivity of the technique (Herth et al. 2004), and linear EBUS with real-time TBNA (EBUS-TBNA) has further improved results by providing direct ultrasonographic visualization while sampling—an approach that is highly accurate with all sizes of nodes (Krasnik et al. 2003). Sensitivities well above 80% and specificities of 100% for lymph node staging have been reported in studies that have used EBUS-TBNA for lung cancer staging (Adams et al., 2009, Cetinkaya et al., 2011, Varela-Lema and Fernández-Villar, 2009, Ye et al., 2011). The negative predictive value (NPV) of the technique for the identification of lung cancer metastases in mediastinal nodes in different studies, however, has been highly variable, ranging from 11–99% (Varela-Lema et al. 2009). These discrepancies may be partly attributable to population characteristics, but factors related to the performance of the procedure probably are significant determinants of the NPV in this setting. Uncertainty relative to the NPV of EBUS-TBNA findings in lung cancer staging, however, complicates therapeutic decisions and has prompted the use of additional preoperative techniques, such as endoscopic ultrasound-guided fine needle aspiration through the esophagus and cervical mediastinoscopy in patients with negative EBUS-TBNA results (Vilmann et al., 2005, Wallace et al., 2008).

The obtention of representative samples of all reachable nodal regions in the mediastinum with EBUS-TBNA is a goal not always attained (Block, 2010, Varela-Lema and Fernández-Villar, 2009), and procedure-related requirements ensuring high NPV for lung cancer staging need to be defined. The aim of the present study was to determine the proportion of EBUS-TBNA procedures that are able to obtain representative samples of both lower paratracheal and subcarinal regions, and to identify EBUS-TBNA performance requirements associated with NPV high enough to consider the technique equivalent to cervical mediastinoscopy in patients with non–small-cell lung cancer (NSCLC), so that therapeutic surgery can be confidently undertaken after an EBUS-TBNA negative for malignancy.

Section snippets

Population

All patients who had a suspicion of lung cancer in North Barcelona Health Area were referred by the general practitioner to the Lung Cancer Unit for diagnosis. EBUS-TBNA was used for mediastinal staging in patients diagnosed with NSCLC who did not show distant metastasis at the first examination. The present study included all NSCLC patients who were staged by means of EBUS-TBNA between 2005 and 2011. A computed tomography (CT) scan of the lung, mediastinum and upper abdomen was performed in

Population and sampling

EBUS-TBNA was used for staging 296 patients with a diagnosis of NSCLC who had a mean age of 63 y (SD ± 10). One-hundred eighty-two (61.5%) showed nodal enlargement on thoracic CT (Table 1). Eight-hundred-three EBUS-TBNA sampling procedures were performed in these patients, 675 (84.1%) on mediastinal and 128 (15.9%) on lobar nodes (Table 2). The median short-axis diameter of the sampled mediastinal and lobar nodes, measured by means of EBUS, was 10 mm (IQR 7 to 14) and 8 mm (IQR 6 to 11),

Discussion

Our study confirms that EBUS-TBNA is an accurate technique for lung cancer staging. Representative sampling of mediastinal regions 4R, 4L and 7 with EBUS-TBNA require the obtention of satisfactory samples, showing lymphocytic and/or malignant cells, from at least one node from each station. This representativeness criteria are attained in >80% of the studied patients through EBUS-TBNA in the present study. In this scenario, the procedure reaches a NPV >90%, equivalent to figures reported for

Acknowledgments

This study has been granted by Fondo de Investigación Sanitaria (FIS) and Fundació Catalana de Pneumologia (FUCAP). The authors thank Adoración Ruiz for her technical assistance during the performance of the procedures. M.E. Kerans assisted with the English expression in versions of the manuscript; her editing fees were covered by funding from Fondo de Investigación Sanitaria.

References (38)

  • K. Adams et al.

    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)
  • J.T. Annema et al.

    Mediastinoscopy vs endosonograpy for mediastinal nodal staging of lung cancer—a randomized trial

    JAMA

    (2010)
  • M. Bernasconi et al.

    Combined transbronchial needle aspiration and positron emission tomography for mediastinal staging of NSCLC

    Eur Respir J

    (2006)
  • British Thoracic Society Guidelines on Diagnostic Flexible Bronchoscopy

    Thorax

    (2001)
  • E. Cetinkaya et al.

    Efficacy of convex probe endobronchial ultrasound (CP-EBUS) assisted tranbronchial needle aspiration for mediastinal staging in non-small cell lung cancer case with mediastinal lymphadenopathy

    Ann Thorac Cardiovasc Surg

    (2011)
  • G.L. Colice

    Chest CT for known or suspected lung cancer

    Chest

    (1994)
  • G.L. Colice et al.

    Physiologic evaluation of the patient with lung cancer being considered for resectional surgery

    Chest

    (2007)
  • P. De Leyn et al.

    ESTS guidelines for preoperative lymph node staging for non-small cell lung cancer

    Eur J Cardiothorac Surg

    (2007)
  • F.C. Detterbeck et al.

    Invasive mediastinal staging of lung cancer

    Chest

    (2007)
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