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SC01 - Staging Before and After Induction Therapy for N2 Disease (ID 325)
- Event: WCLC 2016
- Type: Science Session
- Track: Radiology/Staging/Screening
- Presentations: 1
- Moderators:G. Mostbeck, E. Fadel
- Coordinates: 12/05/2016, 11:00 - 12:30, Lehar 3-4
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SC01.04 - The Role of Mediastinoscopy in Induction Therapy of N2 NCSLC (ID 6601)
11:50 - 12:05 | Author(s): S. Call
- Abstract
Abstract:
Rationale for restaging after induction therapy Persistent mediastinal nodal involvement after induction therapy is an independent prognostic factor associated with poor prognosis [1]. Based on the results of two phase III clinical trials on multimodality treatment for pathologically proven N2 non-small cell lung cancer (NSCLC) [2,3], patients with persistent mediastinal involvement do not benefit from surgical resection in terms of survival. The assessment of an objective response after induction therapy continues to be a diagnostic challenge. For this reason, the use of ‘mediastinal downstaging’ as a criterium to select patients for surgery requires a reliable restaging method to predict pathologic stage before lung resection. Algorithm for mediastinal restaging The European Society of Thoracic Surgeons guidelines for preoperative lymph node staging for NSCLC recommend histological confirmation of objective response after induction therapy. This confirmation can be done with ultrasound-guided endoscopic techniques. However, the use of an invasive surgical technique is still recommended when the results of endoscopic procedures are negative [4]. The role of mediastinoscopy Mediastinoscopy in restaging can be performed in the following situations: 1) after induction therapy with no pretherapeutic invasive diagnosis; 2) after induction therapy with mediastinal histological confirmation by endoscopic techniques; 3) after induction therapy preceded by staging mediastinoscopy. In this case, mediastinoscopy is a reoperation: a remediastinoscopy. The use of first mediastinoscopy for restaging is addressed in a small series [5]. In this article, a negative predictive value (NPV) of 90% with a prevalence of ypN2 of 46% were reported. Theoretically, this approach could be a good strategy to perform an easier and safe mediastinoscopy due to the absence of adhesions in the mediastinum. Remediastinoscopy (reMS) is a technique that does not differ much from a conventional mediastinoscopy. However, reMS is technically more demanding because of peritracheal adhesions, resulting in a lower accuracy in comparison with the first procedure. The main goal of this procedure is to take new biopsies of those nodes that had been positive at first mediastinoscopy. Moreover, if it is technically feasible, other nodal stations should be reached to rule out subclinical progression of the disease. Although reMS is not a common procedure, several authors have reported its feasibility and consistent results (see table 1). In addition, its results do not seem to depend on the type of the induction therapy (chemotherapy or chemoradiation) or on the level of thoroughness of the initial mediastinoscopy [6]. Morbidity rate ranges from 0% to 4%, and complications are not specific of reMS because they can also occur at first mediastinoscopy [1,6-8]. Regarding mortality, only one death has been reported. Based on the four largest published series, this intraoperative death represents a mortality rate of 0.2% [1,6-8]. The role of transcervical lymphadenectomies During the last decade, two new surgical staging procedures were developed: videoassisted mediastinoscopic lymphadenectomy (VAMLA) and transcervical extended mediastinal lymphadenectomy (TEMLA). The main difference between these procedures is that VAMLA is an endoscopic technique performed through a videomediastinoscope, and TEMLA is an open procedure assisted by a videomediastinoscope or a videothoracoscope, depending on the nodal station dissected. Both techniques imply the removal of all the lymph nodes of the explored nodal stations, allowing the identification of minimal nodal disease that is not identified on computed tomography (CT) or positron emission tomography (PET). Therefore, after a properly performed transcervical lymphadenectomy, the restaging of the mediastinum is unnecessary because there is no material left for a new biopsy. Focusing on the use of these procedures for restaging after induction therapy, only TEMLA has been validated on two retrospective studies conducted in the same institution. In the first series with 63 patients, the diagnosis of N2-3 disease before induction treatment was confirmed with invasive techniques in 27 patients (20 with endosonography and 7 with mediastinoscopy), and with CT in 36. Sensitivity, specificity and accuracy of restaging TEMLA were 95.5%, 100% and 98.3%, respectively [9]. In the second series with 176 patients treated with chemo- or chemotherapy, the restaging values of endobronchial endosonography (EBUS) and/or esophageal ultrasonograpy (EUS) (88 patients) were compared with those of TEMLA (78 patients). There was a significant difference between EBUS/EUS and TEMLA for sensitivity (64.3% and 100%; p < 0.01) and NPV (82.1% and 100%; p < 0.01) in favor of TEMLA [10]. Regarding their use for primary staging, VAMLA and TEMLA represent a new paradigm. Firstly, transcervical lymphadenectomies could also be considered part of the induction treatment because the mediastinum is staged and downstaged by these operations. Secondly, due to the fact that nodal restaging is unnecessary, new parameters should be used to select patients for lung resection after induction such as the stability of the primary tumor and the absence of extrathoracic disease based on the results of postinduction CT or PET. Finally, intraoperative pathologic study of the remaining lymph nodes should confirm the absence of nodal involvement before proceeding with lung resection, especially if pneumonectomy is required. Conclusions In multimodality treatments for patients with stage IIIA(N2) tumors, pathologic restaging after induction therapy is essential to decide on subsequent treatment. ReMS is a useful procedure regardless of the induction treatment used or the intensity of the first mediastinoscopy. The role of transcervical lymphadenectomies in staging and restaging should be implemented in clinical practice and validated in future clinical trials. References 1. De Waele M, Serra-Mitjans M, Hendriks J, et al. Accuracy and survival of repeat mediastinoscopy after induction therapy for non-small cell lung cancer in a combined series of 104 patients. Eur J Cardiothorac Surg 2008;33:824-8. 2. 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;99:442-50. 3. 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;374:379-86. 4. De Leyn P, Dooms C, Kuzdzal J, 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. 5. Lardinois D, Schallberger A, Betticher D, et al. Postinduction video-mediastinoscopy is as accurate and safe as video-mediastinoscopy in patients without pretreatment for potentially operable non-small cell lung cancer. Ann Thorac Surg 2003;75:1102–6. 6. Call S, Rami-Porta R, Obiols C, et al. Repeat mediastinoscopy in all its indications: experience with 96 patients and 101 procedures. Eur J Cardiothorac Surg 2011; 39:1022-7. 7. Stamatis G, Fechner S, Hillejan L, et al. Repeat mediastinoscopy as a restaging procedure. Pneumologie 2005;59:862-6. 8. Marra A, Hillejan L, Fechner S, et al. Remediastinoscopy in restaging of lung cancer after induction therapy. J Thorac Cardiovasc Surg 2008;135:843-9. 9. Zieliński M, Hauer L, Hauer J, et al. Non-small-cell lung cancer restaging with transcervical extended mediastinal lymphadenectomy. Eur J Cardiothorac Surg 2010;37:776–80. 10. Zielinski M, Szlubowski A, Kołodziej M, et al. Comparison of endobronchial ultrasound and/or endoesophageal ultrasound with transcervical extended mediastinal lymphadenectomy for staging and restaging of non-small-cell lung cancer. J Thorac Oncol 2013;8:630-6. Table 1. Staging values of the largest published series of remediastinoscopies for restaging after induction therapy.
Abbreviations: N: number of patients; S: Sensitivity; NPV: Negative predictive value; DA: Diagnostic accuracyAuthor Year N S NPV DA Stamatis et al. [7] 2005 160 0.74 0.86 0.92 De Waele et al. [1] 2008 104 0.71 0.73 0.84 Marra et al. [6] 2008 104 0.61 0.85 0.88 Call et al. [8] 2011 84 0.74 0.79 0.87
