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Table of Contents
Year : 2021  |  Volume : 4  |  Issue : 2  |  Page : 360-362

Bridging the gap between guidelines and practice for invasive mediastinal staging in non-small-cell lung cancers

Department of Surgical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India

Date of Submission01-Jun-2021
Date of Decision05-Jun-2021
Date of Acceptance06-Jun-2021
Date of Web Publication30-Jun-2021

Correspondence Address:
Arvind Krishnamurthy
Cancer Institute (WIA), 38, Sardar Patel Road, Adyar, Chennai - 600 036, Tamil Nadu
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/crst.crst_129_21

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How to cite this article:
Krishnamurthy A. Bridging the gap between guidelines and practice for invasive mediastinal staging in non-small-cell lung cancers. Cancer Res Stat Treat 2021;4:360-2

How to cite this URL:
Krishnamurthy A. Bridging the gap between guidelines and practice for invasive mediastinal staging in non-small-cell lung cancers. Cancer Res Stat Treat [serial online] 2021 [cited 2022 Aug 19];4:360-2. Available from: https://www.crstonline.com/text.asp?2021/4/2/360/320174

Lung cancer is one of the leading causes of death globally as well as in the Indian subcontinent. In patients with non-metastatic non-small-cell lung cancers (NSCLCs), involvement of the mediastinal nodes remains the most important prognostic factor. Invasive mediastinal staging better delineates the extent of nodal involvement in patients with NSCLC, who are initially staged by computed tomography (CT) or positron emission tomography (PET)-CT. Mediastinal staging is a prerequisite, not only to accurately assess the prognosis, but also to facilitate proper treatment planning. Clinical practice guidelines generally recommend the confirmation of absence of disease in the mediastinal lymph nodes, prior to embarking on radical surgical resection for patients with lung cancers (barring certain exceptions). Further, patients with neoplastic involvement of the mediastinal lymph nodes (N2/N3 disease) should be considered for multimodality treatment, which may or not may not include radical surgery.[1],[2],[3]

A major limitation of radiological staging in patients with NSCLC is its low accuracy. The presence of a mediastinal lymph node of size > 1 cm and a standardized uptake value higher than that of the mediastinal blood pool on PET-CT imaging are considered predictors of malignant involvement. However, it must be noted that about 20% of the sub-centimeter-sized lymph nodes can harbor an occult malignancy. In addition, a few mediastinal lymph nodes that are not radio avid can also harbor malignancy. The somewhat lower specificity and sensitivity of CT (81% and 55%, respectively) and PET-CT imaging (88 and 80%, respectively) suggest that these imaging modalities can both overstage (false positive due to granulomatous disease including tuberculosis) as well as understage (false negative) the mediastinum in a significant proportion of patients with NSCLC.[1],[2],[3] Thus, there is a perceived need for invasive mediastinal staging in all the patients with non-metastatic NSCLCs, with the possible exception of those with either bulky mediastinal disease or peripheral adenocarcinoma of size <3 cm, with cN0 status.[1],[2],[3],[4] Moreover, practicing clinicians can be alerted about the need to pursue invasive mediastinal staging based on the results of certain risk models that predict the probability of mediastinal nodes harboring metastatic disease.[5]

Cervical mediastinoscopy is considered to be the gold standard for invasive upper mediastinal staging.[6] Lymph node stations corresponding to the para-aortic and the aortopulmonary window, which are considered relatively inaccessible via the conventional mediastinoscopy approaches, can be accessed through extended cervical mediastinoscopy approaches, which include transcervical extended mediastinal lymphadenectomy and video-assisted mediastinal lymphadenectomy.[7]

Over the years, the growing popularity of the endosonographic techniques, which preferably use a combination of endobronchial ultrasound (EBUS) and esophageal ultrasound (EUS), has revolutionized the approach to invasive mediastinal staging.[1],[2],[3] The combined EBUS/EUS approach has the potential to sample almost all the mediastinal lymph node stations. Clinical practice guidelines now recommend that the techniques used to assess the mediastinum should be as minimally invasive as possible to begin with, thus paving the way for the initial use of endosonographic techniques in preference to mediastinoscopy. It is important to note that these clinical practice guidelines acknowledge the moderate-to-low level of evidence that underlies these recommendations.[1],[2],[3]

A similar trend was also observed in the questionnaire-based survey published in this issue of the journal. The authors aimed to study the trends in mediastinal evaluation for lung cancers across India; 82.9% of the respondents preferred EBUS as the initial modality for invasive mediastinal staging.[8] It must be noted that only 20% of the invited clinicians responded to the survey, and the vast majority (84.3%) of them were from academic institutions. This could limit the generalizability of the survey results to general clinical practice. A surprising aspect of the survey results was that mediastinoscopy and EBUS services were reported to be available in the institutions of only 52.9% and 60% of the respondents, respectively. These observations clearly highlight the definite need for enhanced infrastructure to aid clinicians to' better stage and manage their patients with lung cancers.

It must be emphasized that for standard invasive mediastinal staging of patients with lung cancer, both endosonographic techniques (EBUS/EUS) and mediastinoscopy have distinct clinical applications and their roles should at best be considered complementary.[9] Both the procedures have been reported to be safe with low rates of procedure-related complications. However, a few studies suggest that endosonographic techniques are marginally safer.[10] The endosonographic approaches remain invaluable in the decision-making algorithm, especially when the test results are positive; however, the same is not true in the context of a negative test report. The consensus statements of a few earlier studies have reported a 13%–15% probability of identifying metastatic disease in the mediastinal lymph node despite a negative result on endosonography.[11] These findings strongly suggest the need for a confirmatory mediastinoscopy to validate the negative results following endosonography. However, some clinicians do not recommend the practice of confirmatory mediastinoscopy owing to its limited additional diagnostic value.[9],[12] Further, more recent studies suggest an equivalence of the two invasive mediastinal staging techniques.

A recent meta-analysis of 42 studies, including 3248 patients, reported a similar proportion of unforeseen N2 disease with and without a prior cervical mediastinoscopy, following a negative endosonography among patients who underwent radical lung surgery.[12] A more recent meta-analysis interestingly concluded that the performance and safety of EBUS were seemingly adequate to replace mediastinoscopy for invasive mediastinal staging.[13] The results of the ongoing MEDIASTrial[14] will hopefully answer the important question of the additional value of performing a confirmatory mediastinoscopy in patients with NSCLC following a negative endosonography.

Although an increasing number of studies are reporting the equivalence of both the invasive mediastinal staging techniques, it remains unclear whether these encouraging trial results can be effectively reproduced in routine clinical practice.[4],[15] In such a scenario, it is vital for each case of non-metastatic NSCLC to be deliberated in a multidisciplinary tumor board. The multidisciplinary board should consider a wide range of issues and variables, including those pertaining to the characteristics of the primary tumor and lymph nodes on PET-CT scans as well as other factors pertaining to the availability and in-house expertise in performing both the invasive mediastinal staging procedures.

It is vitally important for the treating clinicians to strive to achieve optimal results when performing mediastinal endosonography and mediastinoscopy, by adhering to the prescribed international standards. The quality of the invasive mediastinal testing would largely depend on the quality of the equipment, availability of well-trained and experienced operator teams, and the added availability of rapid-onsite cytology (ROSE). It must be emphasized that greater skills and expertise are required for mediastinal restaging, in view of the tumor fibrosis and necrosis following induction therapy, although the general principles of imaging and sampling remain the same.

In conclusion, accurate mediastinal lymph node staging can help ensure the optimal management of patients with non-metastatic NSCLCs, by avoiding the potential dangers of under and over staging. Although clinical practice guidelines from numerous organizations are available to guide the clinicians about the science and practice of invasive mediastinal staging, there seems to be a great deal of variability and possible underutilization of these services in a sizable proportion of patients with NSCLC, as was highlighted by the questionnaire-based survey. A low threshold for reviewing complex cases of non-metastatic NSCLCs in a committed multi-disciplinary tumor board and an enhanced infrastructure in every institution managing patients with lung cancers can possibly help bridge the quality gap between the clinical practice guidelines and routine clinical practice. Practicing clinicians in India thus need to adopt a pragmatic approach toward the use of invasive mediastinal staging in the management of patients with lung cancers.

  References Top

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De Leyn P, Dooms C, Kuzdzal J, Lardinois D, Passlick B, Rami-Porta R, et al. Revised ESTS guidelines for preoperative mediastinal lymph node staging for non-small-cell lung cancer. Eur J Cardiothorac Surg 2014;45:787-98.  Back to cited text no. 2
Vilmann P, Clementsen PF, Colella S, Siemsen M, De Leyn P, Dumonceau JM, et al. Combined endobronchial and esophageal endosonography for the diagnosis and staging of lung cancer: European Society of Gastrointestinal Endoscopy (ESGE) Guideline, in cooperation with the European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS). Endoscopy 2015;47:545-59.  Back to cited text no. 3
Osarogiagbon RU, Lee YS, Faris NR, Ray MA, Ojeabulu PO, Smeltzer MP. Invasive mediastinal staging for resected non-small cell lung cancer in a population-based cohort. J Thorac Cardiovasc Surg 2019;158:1220-9.e2.  Back to cited text no. 4
Martinez-Zayas G, Almeida FA, Simoff MJ, Yarmus L, Molina S, Young B, et al. A Prediction model to help with oncologic mediastinal evaluation for radiation: HOMER. Am J Respir Crit Care Med 2020;201:212-23.  Back to cited text no. 5
D'Andrilli A, Maurizi G, Venuta F, Rendina EA. Mediastinal staging: When and how? Gen Thorac Cardiovasc Surg 2020;68:725-32.  Back to cited text no. 6
Call S, Rami-Porta R. Cervical mediastinoscopy and video-assisted mediastinoscopic lymphadenectomy for the staging of non-small cell lung cancer. Mediastinum 2019;3:31.  Back to cited text no. 7
Chandveettil J, Kattepur A, Pareekutty NM, Kumbakara R, Balasubramanian S. Changing trends of invasive mediastinal evaluation in India: A questionnaire-based survey. Cancer Res Stat Treat 2021: 4:231-7.  Back to cited text no. 8
Kuijvenhoven JC, Korevaar DA, Tournoy KG, Malfait TL, Dooms C, Rintoul RC, et al. Five-year survival after endosonography vs mediastinoscopy for mediastinal nodal staging of lung cancer. JAMA 2016;316:1110-2.  Back to cited text no. 9
Verdial FC, Berfield KS, Wood DE, Mulligan MS, Roth JA, Francis DO, et al. Safety and costs of endobronchial ultrasound-guided nodal aspiration and mediastinoscopy. Chest 2020;157:686-93.  Back to cited text no. 10
Leiro-Fernández V, Fernández-Villar A. Mediastinal staging for non-small cell lung cancer. Transl Lung Cancer Res 2021;10:496-505.  Back to cited text no. 11
Bousema JE, van Dorp M, Noyez VJ, Dijkgraaf MG, Annema JT, van den Broek FJ. Unforeseen N2 disease after negative endosonography findings with or without confirmatory mediastinoscopy in resectable non-small cell lung cancer: A systematic review and meta-analysis. J Thorac Oncol 2019;14:979-92.  Back to cited text no. 12
Figueiredo VR, Cardoso PF, Jacomelli M, Santos LM, Minata M, Terra RM. EBUS-TBNA versus surgical mediastinoscopy for mediastinal lymph node staging in potentially operable non-small cell lung cancer: A systematic review and meta-analysis. J Bras Pneumol 2020;46:E20190221.  Back to cited text no. 13
Bousema JE, Annema JT, van der Heijden EH, Verhagen AF, Dijkgraaf MG, van den Broek FJ. MEDIASTrial study group. MEDIASTinal staging of non-small cell lung cancer by endobronchial and endoscopic ultrasonography with or without additional surgical mediastinoscopy (MEDIASTrial): A statistical analysis plan. Trials 2021;22:168.  Back to cited text no. 14
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