Preoperative Mediastinal Lymph Node Staging for Non-small Cell Lung Cancer

2014 Update of the 2007 ESTS Guidelines

Paul De Leyn; Christophe Dooms; Jaroslaw Kuzdzal; Didier Lardinois; Bernward Passlick; Ramon Rami-Porta; Akif Turna; Paul Van Schil; Frederico Venuta; David Waller; Walter Weder; Marcin Zielinski

Disclosures

Transl Lung Cancer Res. 2014;3(4):225-233. 

In This Article

Surgical Staging Techniquesother Section

Cervical Mediastinoscopy

Cervical mediastinoscopy through a pretracheal suprasternal incision was introduced by Carlens in 1959 and further popularized by Pearson in North America. It allows a full mapping of the ipsilateral and contralateral superior mediastinal lymph nodes. Cervical mediastinoscopy is performed under general anaesthesia and can be safely done as an outpatient procedure. For many years it was the gold standard for invasive staging of patients with potentially operable lung cancer. Since 1995, use of video techniques has been introduced leading to video-assisted mediastinoscopy (VAM). VAM clearly improved visualization and teaching[33] since both the trainer and the trainee can share the magnified image on the monitor. For more details on the technique of cervical mediastinoscopy, we refer to a recent publication on this topic.[34]

There are only retrospective studies comparing the safety and accuracy of conventional mediastinoscopy with VAM. Although some authors[35–37] found an increase in the number of LN or LN stations biopsied, no difference in sensitivity or NPV was found. In some of these studies a reduction in the complication rate (mainly of recurrent nerve palsy) was observed. Very recently,[38] a best evidence topic has been published on the safety and accuracy of VAM compared to conventional mediastinoscopy (Table 3). The authors analysed 108 papers published between 1989 and 2011. There were 5,156 conventional mediastinoscopies and 956 VAMs. Both procedures are safe with no mortality in that time frame and a low morbidity. Although by VAM more lymph node stations are sampled, the negative predictive value and accuracy were identical.

Although the video-mediastinoscope is not strictly necessary to achieve a thorough, clinically acceptable mediastinoscopy, it has many advantages over the conventional one: larger and clearer images, the possibility to simultaneously share the procedure with trainees and all the personnel in the operative theatre, the possibility to record the operation for future educational uses and discussion, and the possibility to improve its teaching without compromising the safety or accuracy of the procedure. Moreover it allows bimanual dissection with possibilities to perform nodal dissection and removal rather than sampling or biopsy. This is especially important and technically feasible for the subcarinal LN station. After removal of station 7 LNs, the oesophagus can be clearly visualized. The ESTS working group recommends performing VAM.

Video-assisted Thoracoscopic Surgery (VATS)

Although VATS can reach almost every mediastinal lymph node station, it is more invasive than cervical mediastinoscopy (it needs double lumen intubatio), it is limited by pleural adhesions, and it can only evaluate ipsilateral nodal disease. For the para-aortic lymph nodes (station 6) and the subaortic lymph nodes (station 5), left VATS is a surgical technique that allows obtaining large tissue samples. It is indicated when enlarged PET positive lymph nodes are visualized at level 5 or 6. These lymph node stations cannot be biopsied by routine mediastinoscopy, E(B)US-FNA. An alternative to VATS is the left anterior mediastinotomy. In some experienced centres, extended mediastinoscopy from the mediastinoscopy incision is performed for these lymph node stations and it gives good negative predictive values: 0.89–0.97.[34]

Video-assisted Mediastinoscopic Lymphadenectomy (VAMLA) Transcervical Extended Mediastinal Lymphadenectomy (TEMLA)

During the last decade, two new invasive staging techniques representing more radical methods of mediastinal exploration have been introduced: VAMLA[39] and TEMLA.[40] These two techniques aim for a complete removal of all the mediastinal nodes with the surrounding adipose tissue to improve the accuracy of staging. VAMLA is completely performed with the use of the videomediastinoscope whilst TEMLA uses a 5–8 cm collar incision in the neck and elevates the sternum with a hook. The dissection is performed in an open way and with the use of the videomediastinoscope. By VAMLA, the lymph nodes which are usually accessible through mediastinoscopy, are removed. By TEMLA, more lymph node stations are accessible such as the prevascular, the para-aortic, the subaortic and the para-oesophageal lymph node stations. The negative predictive value is very high and approaches 98.7% for TEMLA. Although there is no doubt that the accuracy of mediastinal staging increases when lymphadenectomy is performed compared to nodal biopsy, these techniques have a higher morbidity and mortality. The complications after VAMLA and TEMLA are well recorded and are probably more studied in detail than after CM or VAM. These procedures are performed in very experienced centres. For VAMLA mainly problems with recurrent nerve palsy and important scarring with an impact on subsequent resection are reported.[39,41–44] The published data for TEMLA are mainly from one very experienced centre and there are concerns on morbidity and mortality.

For TEMLA and VAMLA we conclude that currently available data regarding its use are limited and, therefore, we do not recommend its use except of clinical trials. We encourage other centres to publish their data with these new staging techniques.

The algorithm for preoperative mediastinal staging is shown in Figure 1. For NSCLC, both for mediastinal as for distant staging, PET or PET-CT is indicated.

Figure 1.

Revised ESTS guideline for primary mediastinal staging (De Leyn et al., European Journal of Cardiothoracic Surgery 2014;45:787–798 with permission). (a), in tumours >3 cm (mainly in adenocarcinoma with high FDG uptake) invasive staging should be considered; (b), depending on local expertise to adhere to minimal requirements for staging; (c), endoscopic techniques are minimally invasive and are the first choice if local expertise with EBUS/EUS needle aspiration is available; (d), due to its higher NPV, in case of PET positive or CT enlarged mediastinal LN's, videoassisted mediastinoscopy (VAM) with nodal dissection or biopsy remain indicated when endoscopic staging is negative. Nodal dissection has an increased accuracy over biopsy.

  • Direct surgery can be performed if all of these three criteria apply: no suspect lymph node detected by CT or PET, a tumor ≤3 cm (stage IA), located in the outer third of the lung (level IIA).

  • In case of enlarged mediastinal lymph nodes on CT or PET-positive lymph nodes, tissue confirmation is indicated. In this case, endosonography (EBUS/EUS) with fine needle aspiration is the first choice (when available) since it is minimally invasive and has a high sensitivity to rule in mediastinal nodal disease (level IA). If negative, video-assisted mediastinoscopy is indicated (level IB). The combined use of endoscopic staging and surgical staging results in the highest accuracy.

For patients with a left upper lobe tumour, surgical staging of the aorto-pulmonary window nodes (if enlarged on CT and/or PET-CT-positive) can be performed (by anterior mediastinotomy, VATS or extended cervical mediastinoscopy) if involvement changes treatment strategy (level V).

  • Invasive staging by E(B)US/mediastinoscopy is indicated if at least one of these criteria apply: central lesion, suspect N1 nodes (level IIB). In case of tumors >3 cm (mainly in adenocarcinoma with high FDG uptake) the negative predictive value for mediastinal nodal disease is <90% and invasive staging may be considered (level IIB). Although a high FDG update in the primary tumor is a predictor of N2 disease, the ideal cutoff of SUV value has not yet been determined above which invasive mediastinal nodal staging is required. In addition, the SUV measurement is not yet standardized from one center to another and therefore a visual interpretation of the FDG uptake on PET is to be preferred (Dooms 2010). In all of the above-mentioned cases there is the choice between VAM with biopsy or lymph node dissection or endoscopic staging by EBUS/EUS with fine needle aspiration. The choice depends on local expertise to adhere to minimal requirements for staging (level V). If video-assisted mediastinoscopy is negative, these patients can undergo surgical treatment. They also can undergo surgical treatment after negative EBUS/EUS if the number of nodes explored and the number of needle passes in each node meet the established requirements. Otherwise, surgical exploration is recommended after negative EBUS/EUS.

  • If only CT is available, we refer to the algorithm of the 2007 edition of the ESTS guidelines (De Leyn 2007).

We conclude that optimal mediastinal lymph node staging is a truly multidisciplinary process, with a variety of possible techniques, to be performed by experienced hands.

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