Five-Year Survival After Endosonography vs Mediastinoscopy for Mediastinal Nodal Staging of Lung Cancer | Cardiothoracic Surgery | JAMA | JAMA Network
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Figure.  Survival Among Patients With Lung Cancer in the Endosonographic vs Surgical Staging Strategies
Survival Among Patients With Lung Cancer in the Endosonographic vs Surgical Staging Strategies

Adjusted for mediastinal nodal metastases status (N0/N1 vs N2/N3) (adjusted hazard ratio, 0.98 [95% CI, 0.73-1.32]). The median duration of follow-up was 33 months (interquartile range [IQR], 13-76) for surgical staging and 31 months (IQR, 13-75) for endosonographic staging.

Table.  Survival Among Patients With Lung Cancer in the Endosonographic vs the Surgical (Mediastinoscopy) Staging Strategiesa
Survival Among Patients With Lung Cancer in the Endosonographic vs the Surgical (Mediastinoscopy) Staging Strategiesa
1.
Torre  LA, Bray  F, Siegel  RL, Ferlay  J, Lortet-Tieulent  J, Jemal  A.  Global cancer statistics, 2012.  CA Cancer J Clin. 2015;65(2):87-108.PubMedGoogle ScholarCrossref
2.
Vilmann  P, Clementsen  PF, Colella  S,  et al.  Combined endobronchial and oesophageal endosonography for the diagnosis and staging of lung cancer.  Eur Respir J. 2015;46(1):40-60.PubMedGoogle ScholarCrossref
3.
Silvestri  GA, Gonzalez  AV, Jantz  MA,  et al.  Methods for staging non-small cell lung cancer.  Chest.2013;143(5 suppl):e211S-250S. PubMedGoogle ScholarCrossref
4.
Annema  JT, van Meerbeeck  JP, Rintoul  RC,  et al.  Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer.  JAMA. 2010;304(20):2245-2252.PubMedGoogle ScholarCrossref
5.
Navani  N, Nankivell  M, Lawrence  DR,  et al.  Lung cancer diagnosis and staging with endobronchial ultrasound-guided transbronchial needle aspiration compared with conventional approaches.  Lancet Respir Med. 2015;3(4):282-289.PubMedGoogle ScholarCrossref
Research Letter
September 13, 2016

Five-Year Survival After Endosonography vs Mediastinoscopy for Mediastinal Nodal Staging of Lung Cancer

Author Affiliations
  • 1Department of Respiratory Medicine, Academic Medical Center, Amsterdam, the Netherlands
  • 2Department of Clinical Epidemiology, Biostatistics, and Bioinformatics, Academic Medical Center, Amsterdam, the Netherlands
  • 3Department of Respiratory Medicine, Onze-Lieve-Vrouw Hospital, Aalst, Belgium
  • 4Department of Respiratory Medicine, University Hospital Ghent, Ghent, Belgium
  • 5Department of Respiratory Medicine, Leuven University Hospitals, Leuven, Belgium
  • 6Papworth Clinical Trials Unit Collaboration, Papworth Hospital, Cambridge, United Kingdom
JAMA. 2016;316(10):1110-1112. doi:10.1001/jama.2016.10349

Lung cancer accounts for the highest cancer-related mortality rate worldwide.1 Accurate mediastinal nodal staging is crucial in the management of non–small cell lung cancer (NSCLC) because it directs therapy and has prognostic value.2,3

The Assessment of Surgical Staging vs Endosonographic Ultrasound in Lung Cancer (ASTER) trial compared mediastinoscopy (surgical staging) with an endosonographic staging strategy (which combined the use of endobronchial and transesophageal ultrasound followed by mediastinoscopy if negative).4 The endosonographic strategy was significantly more sensitive for diagnosing mediastinal nodal metastases than surgical staging (94% endosonographic strategy vs 79% surgical strategy).

If mediastinal staging is improved, more patients should receive optimal treatment and might survive longer. The current post hoc analysis evaluated survival in ASTER.

Methods

At inclusion in ASTER, all participants provided written informed consent; the current analysis was either approved or waived by the involved ethical committees. Of 241 patients with potentially resectable NSCLC, 123 were randomized to endosonographic staging and 118 to surgical staging in 4 tertiary referral centers in Leiden (the Netherlands), Ghent and Leuven (Belgium), and Cambridge (United Kingdom) between February 2007 and April 2009.4 Surgical-pathological staging was the reference standard for mediastinal nodal assessment.

Between June 30, 2015, and October 15, 2015, survival data were obtained through patient records, death registers, or contact with general practitioners (trial protocol in the Supplement).

The proportion of survivors at 5 years for both staging strategies and odds ratios (ORs) with 95% CIs were calculated. Kaplan-Meier analysis was performed and hazard ratios were calculated to compare survival between the strategies, adjusting for mediastinal nodal metastases in a Cox proportional hazards model. Survival for patients with no date of death were censored on the date last known to be alive. The assumption of proportional hazard was tested and met. Subgroup analysis was performed for patients with nodal stages N2/N3 and N0/N1. Data were analyzed using SPSS Statistics (IBM), version 22.0.

Results

Survival data at 5 years were obtained for 237 of 241 patients (98%); 2 patients in both groups were lost to follow-up. There were 182 men (77%) with a mean age at randomization of 65 years (SD, 9). Detailed patient characteristics were previously reported.4 The prevalence of mediastinal nodal metastases was 54% in the endosonographic strategy group and 44% in the surgical strategy group.

Survival at 5 years was 35% (42 of 121 patients) for the endosonographic strategy vs 35% (41 of 116 patients) for the surgical strategy (OR, 0.97 [95% CI, 0.57-1.66]) (Table). The estimated median survival was 31 months (95% CI, 21-41) for the endosonographic strategy vs 33 months (95% CI, 23-43) for the surgical strategy (adjusted hazard ratio, 0.98 [95% CI, 0.73-1.32]) (Figure).

In the subgroup with N2/N3 metastases, survival was 17% (11 of 64 patients) in the endosonographic strategy vs 19% (10 of 52 patients) in the surgical strategy (OR, 0.87 [95% CI, 0.34-2.25]). In the subgroup with N0/N1 metastases, survival was 54% (31 of 57 patients) for the endosonographic strategy vs 48% (31 of 64 patients) for the surgical strategy (OR, 1.27 [95% CI, 0.62-2.60]).

Discussion

No survival difference was found 5 years following randomization to an endosonographic or surgical staging strategy for patients with NSCLC. Since the original results of ASTER were published, clinical guidelines on lung cancer management underwent major revisions and now advocate endosonography instead of mediastinoscopy as the initial step for mediastinal nodal staging.2,3 The endosonographic strategy is more accurate, less invasive, and reduces unnecessary thoracotomies.4

Data from a recent randomized trial show prolonged survival in patients who underwent endosonography compared with conventional staging.5 However, most patients in the latter group underwent bronchoscopy instead of mediastinoscopy.

Why did improved mediastinal staging not lead to improved survival? Missing data occurred in less than 2% and therefore are an unlikely source of bias. However, ASTER was powered to detect a difference in diagnostic sensitivity, not survival, as reflected by the wide confidence intervals. If a survival difference between the strategies exists, it is likely to be small and a larger sample size may be needed to detect it. However, randomized trials to detect a survival difference based on staging strategy are not likely to be conducted as the endosonographic strategy is now advised in clinical guidelines.2,3

Section Editor: Jody W. Zylke, MD, Deputy Editor.
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Article Information

Corresponding Author: Jouke T. Annema, MD, PhD, Department of Respiratory Medicine, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, the Netherlands (j.t.annema@amc.uva.nl).

Author Contributions: Dr Kuijvenhoven had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Kuijvenhoven, Tournoy, Annema.
Acquisition, analysis, or interpretation of data: All Authors.
Drafting of the manuscript: Kuijvenhoven, Korevaar, Tournoy, Annema.
Critical revision of the manuscript for important intellectual content: Tournoy, Malfait, Dooms, Rintoul, Annema.
Statistical analysis: Kuijvenhoven, Korevaar, Tournoy.
Administrative, technical, or material support: Malfait.
Study supervision: Tournoy, Annema.
No additional contributions: Dooms, Rintoul.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Annema reports receiving material and financial support for educational endobronchial and esophageal ultrasound courses from Hitachi, Pentax, COOK and Symbionix to the department of respiratory medicine at his institution. Dr Rintoul reports receiving financial support for educational endobronchial and esophageal ultrasound courses from Olympus to his institution. No other disclosures were reported.

Funding/Support: The ASTER trial was supported by local support for data collection at Ghent University Hospital, the Zorgprogramma Oncologie Gent, and by the National Institute for Health Research Cambridge Biomedical Research Centre (Dr Rintoul). Data collection in Papworth Hospital was supported by the UK National Health Service R&D Health Technology Assessment Program (project No. 06/302/216). No specific funding was sought for this post hoc analysis.

Role of the Funder/Sponsor: The funders of the original ASTER trial had no role in the design and conduct of this post hoc analysis; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Trial Registration: clinicaltrials.gov Identifier: NCT00432640

References
1.
Torre  LA, Bray  F, Siegel  RL, Ferlay  J, Lortet-Tieulent  J, Jemal  A.  Global cancer statistics, 2012.  CA Cancer J Clin. 2015;65(2):87-108.PubMedGoogle ScholarCrossref
2.
Vilmann  P, Clementsen  PF, Colella  S,  et al.  Combined endobronchial and oesophageal endosonography for the diagnosis and staging of lung cancer.  Eur Respir J. 2015;46(1):40-60.PubMedGoogle ScholarCrossref
3.
Silvestri  GA, Gonzalez  AV, Jantz  MA,  et al.  Methods for staging non-small cell lung cancer.  Chest.2013;143(5 suppl):e211S-250S. PubMedGoogle ScholarCrossref
4.
Annema  JT, van Meerbeeck  JP, Rintoul  RC,  et al.  Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer.  JAMA. 2010;304(20):2245-2252.PubMedGoogle ScholarCrossref
5.
Navani  N, Nankivell  M, Lawrence  DR,  et al.  Lung cancer diagnosis and staging with endobronchial ultrasound-guided transbronchial needle aspiration compared with conventional approaches.  Lancet Respir Med. 2015;3(4):282-289.PubMedGoogle ScholarCrossref
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