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Accurate mediastinal lymph node staging is critical to inform on the management of patients with early stage lung cancer and is usually undertaken in the setting where surgery is being considered as a management option.

Views on the appropriateness of surgery in patients with N2 disease are varied. Some clinicians carry a prevailing view that patients with N2 disease are not suitable due to poor overall survival. However, after induction treatment, there were no differences in overall survival in randomized trials comparing surgery to radiotherapy.1–4 These results suggest equipoise in defining optimum management for patients with N2 disease, and surgery as a valid option. In fact, in the Albain et al. study after induction chemoradiotherapy patients in the surgery arm had significantly better progression-free survival.4

The spectrum of N2 disease is as varied as the number of different management options, ranging from microscopic to fixed bulky disease. The former is not usually detected prior to thoracotomy and patients with the latter are not offered surgery as a management option. Therefore, most clinical decisions are based on tissue confirmation of the site and distribution of N2 disease detected by computed tomography (CT), positron emission tomography (PET) or PET/CT criteria.

Diagnostic fine needle aspiration of paratracheal masses began as early as 1978,5,6 but as technology improved, smaller and more flexible aspiration needles were manufactured for use within a flexible bronchoscope.5 The development of endobronchial ultrasound (EBUS) became a significant complimentary advancement, with a convex probe facilitating real-time EBUS-guided transbronchial needle aspiration (EBUS-TBNA) of mediastinal and hilar lymph nodes. Today, EBUS-TBNA is becoming increasingly available for mediastinal lymph node staging in patients with known or suspected lung cancer.

We recently conducted a systematic review and meta-analysis of 10 suitable studies that fit our selection criteria out of 365 publications from 1950 to 2008. The point specificity of EBUS-TBNA to detect N2 disease was 1.00 (95% confidence interval [CI] 0.92–1.00) and the point sensitivity was 0.88 (95% CI 0.79–0.94). The discriminating ability of EBUS-TBNA was excellent, as assessed by the area under the summary receiver operating characteristics curve of 0.99 (95% CI 0.96–1.00).7 The specificity of 100% is easily explained, as tests that involve tissue biopsy false positive results are rare (ie diagnosis of cancer in normal lymph nodes).

Given the excellent test performance of EBUS-TBNA, what is its role for staging lung cancer? The favorable published results of EBUS-TBNA compared to both CT and PET do 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. Current published evidence has been generated from a handful of experts and it is not realistic to assume a similar test performance across the board until appropriate experience and expertise has been acquired more widely. In addition, EBUS-TBNA can assess only access lymph node stations in close proximity to the airway, such as the paratracheal and subcarinal stations (although a greater reach is possible with the complementary use of endoscopic ultrasound [EUS]).

In general, many clinicians use PET/CT as the first line for mediastinal lymph node staging, reserving blind TBNA, EBUS-TBNA and EUS to confirm or refute the finding of PET/CT. How rigorously the mediastinum should be staged depends on the clinicians' and patients' attitudes towards surgery as a management modality for N2 disease. If there is a permissive attitude towards recommending surgery for patients with PET/CT positive N2 disease it could be argued that further tissue sampling is not required. On the other hand, if there is a restrictive approach to surgery as a treatment modality, then all efforts are directed at confirming N2 disease identified on PET/CT. This can involve blind TBNA, EBUS-TBNA or EUS and needle aspiration where available, and with a specificity of 100%, it can be assumed that all patients with a positive result have lymph node metastasis. However, with a pooled sensitivity of 0.93, it can be expected that 7% of patients with N2 disease have a false negative result. Therefore, if the results of the EBUS-TBNA are negative, confirmatory mediastinoscopy and lymph node biopsies will be required. The role of EBUS-TBNA in the middle ground, where surgery is offered to selected patients based on response to initial induction treatment, is much harder to define, as there is insufficient evidence in this area. Intuitively the specificity (ability to rule in N2 disease) of 100% should not change based on the reasons outlined above, however the results with regards to sensitivity (ability to rule out disease) is undefined.

The introduction of EBUS-TBNA offers a new and exciting modality to stage the mediastinum. Its role is best defined in conjunction with availability, expertise and, most importantly, attitudes towards the (surgical) management of patients with N2 disease.

References

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  2. References
  • 1
    Johnstone DW, Byhardt RW, Ettinger D, Scott CB. Phase III study comparing chemotherapy and radiotherapy with preoperative chemotherapy and surgical resection in patients with non-small-cell lung cancer with spread to mediastinal lymph nodes (N2); final report of RTOG 89-01. Radiation Therapy Oncology Group. Int J Radiat Oncol Biol Phys 2002; 54: 3659.
  • 2
    Shepherd FA, Johnston MR, Payne D et al. Randomized study of chemotherapy and surgery versus radiotherapy for stage IIIA non-small-cell lung cancer: a National Cancer Institute of Canada Clinical Trials Group Study. Br J Cancer 1998; 78: 6835.
  • 3
    Van Meerbeeck JP, Kramer GW, Van Schil PE et al. Randomized controlled trial of resection versus radiotherapy after induction chemotherapy in stage IIIA-N2 non-small-cell lung cancer. J Natl Cancer Inst 2007; 99: 44250.
  • 4
    Albain KS, Swann RS, Rusch VW et al. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet 2009; 374: 37986.
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    Herth F, Becker HD, Manegold C, Drings P. Endobronchial ultrasound EBUS–assessment of a new diagnostic tool in bronchoscopy for staging of lung cancer. Onkologie 2001; 24: 1514.
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    Whyte RI. Advances in the staging of intrathoracic malignancies. World J Surg 2001; 25: 16773.
  • 7
    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: 75762.