What is the clinical benefit of mediastinal lymph node dissection in stage IIIA operable NSCLC?

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Introduction

Jutta's info icon.png Defining operable and inoperable disease in stage III

The management of Stage III NSCLC has been divided into sections dependent on whether the disease is considered operable or inoperable at the time of diagnosis.

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Stage III NSCLC encompasses a broad spectrum of disease extent from tumour involving a single nodal station identified only postoperatively despite extensive pre-operative staging to involvement of multiple contralateral mediastinal nodes and supraclavicular nodes appreciated on clinical examination. In patients with clinically equivocal involvement, pathological confirmation of nodal status should be made if it will influence management options.

The decision as to operability should be made in a multidisciplinary setting.

Patients with Stage III NSCLC may be deemed inoperable because of patient factors (the patient’s respiratory function or co-morbidities may preclude operative intervention or the patient may choose not to proceed with surgery) or tumour factors (the extent or location of gross disease might make surgical resection technically impossible, for example left sided tumours with mediastinal nodes to the right of the aorta, N3 nodal involvement and most T4 tumours).

In the absence of other factors precluding surgery, patients with N1 disease should be considered for surgery. Patients with confirmed N2 disease should not be treated by surgery as the sole modality, but resectable cases may be considered for a multimodality approach. There is no consensus on the distinction between resectable and unresectable N2 disease. Factors influencing assessment of resectability include nodal size, number of stations involved, extracapsular extension and involvement of the recurrent laryngeal nerve.

This evidence relates to patients who have had standard therapy with at least lobectomy and lymph node sampling. Mediastinal lymph node staging, either by pre-operative (mediastinoscopy, endobronchial ultrasound FNA) or intra-operative sampling is an integral part of surgical resection of NSCLC. Besides the prognostic value of proper staging, the current evidence base for adjuvant chemotherapy shows a survival advantage for patients receiving chemotherapy if any nodes are found to be positive.


Complete lymph node dissection versus lymph node staging in stage IIIA

Whilst accurate lymph node staging should be standard practice, the evidence to date has been unclear as to when a complete mediastinal lymph node dissection is indicated, if at all. In a Cochrane review by Manser et al[1], it was found that the evidence already existed for a survival benefit from complete mediastinal lymph node dissection. This was specifically reported in 2006[2], but did not generate the level of interest that accompanies new pharmacological interventions. The randomised trials by Wu et al[3] and Passlick et al[4] showed an increasing benefit for higher stage disease, but the Will Rogers phenomenon of stage migration could not be ruled out as a source of bias. It was not until the publication of the American College of Surgeons Oncology Group Z30 trial[5], that it could be inferred that the benefit of complete mediastinal dissection is clearest in stage II and higher NSCLC.

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Evidence summary and recommendations

Evidence summary Level References
Complete mediastinal lymph node dissection is associated with improved overall survival compared to lymph node staging alone in patients with unknown stage or stage II-IIIA surgically resected NSCLC. I, II [1], [2], [6], [3], [4]
Recommendation Grade
A complete mediastinal lymph node dissection of at least Stations 2R, 4R, 7 and 8 (right side) or Stations 5, 6, 7 and 8 (left side) is recommended for surgically resected stage IIIA NSCLC.
B

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References

  1. 1.0 1.1 Manser R, Wright G, Hart D, Byrnes G, Campbell DA. Surgery for early stage non-small cell lung cancer. Cochrane Database Syst Rev 2005 Jan 25;(1):CD004699 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/15674959].
  2. 2.0 2.1 Wright G, Manser RL, Byrnes G, Hart D, Campbell DA. Surgery for non-small cell lung cancer: systematic review and meta-analysis of randomised controlled trials. Thorax 2006 Jul;61(7):597-603 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/16449262].
  3. 3.0 3.1 Wu Y, Huang ZF, Wang SY, Yang XN, Ou W. A randomized trial of systematic nodal dissection in resectable non-small cell lung cancer. Lung Cancer 2002 Apr;36(1):1-6 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11891025].
  4. 4.0 4.1 Passlick B, Kubuschock B, Sienel W, Thetter O, Pantel K, Izbicki JR. Mediastinal lymphadenectomy in non-small cell lung cancer: effectiveness in patients with or without nodal micrometastases - results of a preliminary study. Eur J Cardiothorac Surg 2002 Mar;21(3):520-6 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11888774].
  5. Darling GE, Allen MS, Decker PA, Ballman K, Malthaner RA, Inculet RI, et al. Randomized trial of mediastinal lymph node sampling versus complete lymphadenectomy during pulmonary resection in the patient with N0 or N1 (less than hilar) non-small cell carcinoma: Results of the American College of Surgery Oncology Group Z0030 Trial. J Thorac Cardiovasc Surg 2011 Mar;141(3):662-70 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21335122].
  6. Hughes MJ, Chowdhry MF, Woolley SM, Walker WS. In patients undergoing lung resection for non-small cell lung cancer, is lymph node dissection or sampling superior? Interact Cardiovasc Thorac Surg 2011 Sep;13(3):311-5 [Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21606053].

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Appendices

Further resources

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