Video-assisted mediastinoscopic lymphadenectomy (VAMLA): Mature results for staging non-small cell lung cancer with normal mediastinum.

OBJECTIVES: The aim of this study is to analyze the accuracy of video-assisted mediastinoscopic lymphadenectomy (VAMLA) and the unsuspected (u) N2/3 rates in patients with non-small cell lung cancer (NSCLC) and normal mediastinum by integrated positron emission tomography-computed tomography. METHODS: Prospective observational single-center study of 603 consecutive VAMLAs from 2010 to 2022. EXCLUSION CRITERIA: other indications (n = 32), tumors different from NSCLC (n = 91), and clinical (c) N2/3 tumors by positron emission tomography-computed tomography (n = 46). Systematic nodal dissection was the gold standard to validate negative VAMLAs. Those patients with negative VAMLA and missing reference standard test were excluded. uN2/3 rates were analyzed in the global series and in the subgroups of tumors according to their clinical nodal and tumor categories. Pathologic findings were reviewed, and staging values were calculated. RESULTS: Three hundred eighty-three patients with cN0/1 NSCLC underwent VAMLA. Staging values of VAMLA were: sensitivity, 0.98 (95% CI, 0.92-0.99); negative predictive value, 0.99 (95% CI, 0.98-1); and diagnostic accuracy, 0.99 (95% CI, 0.98-1). The uN2/3 rate for the whole series (N = 383) was 18.8%. The uN2/3 rates according to presurgical nodal and tumor categories determined by positron emission tomography computed tomography were: 3.6% (4 out of 111) in cT1N0; 16.3% (18 out of 110) in cT2N0; 10.25% (4 out of 39) in cT3N0; and 32% (7 out of 22) in cT4N0. Forty-two percent (39 out of 93) in cN1; complication rate was 7%. CONCLUSIONS: This series of NSCLC with normal mediastinum staged by VAMLA demonstrates a high accuracy of this technique and a high rate of uN2/3 disease (specially in cN1 and cT4N0). VAMLA could be considered the reference staging procedure for staging cN0/1 NSCLC.

EBUS-TBNA for mediastinal staging of centrally located T1N0M0 non-small cell lung cancer clinically staged with PET/CT.

BACKGROUND AND OBJECTIVE: To evaluate the diagnostic accuracy and clinical usefulness of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal staging of centrally located T1N0M0 non-small cell lung cancer (NSCLC) clinically staged with positron emission tomography/computed tomography (PET/CT). METHODS: We conducted a study that included patients with centrally located T1N0M0 NSCLC, clinically staged with PET/CT who underwent EBUS-TBNA for mediastinal staging. Patients with negative EBUS-TBNA underwent mediastinoscopy, video-assisted mediastinoscopic lymphadenectomy (VAMLA) and/or lung resection with systematic nodal dissection, that were considered the gold standard. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), overall accuracy of EBUS-TBNA for diagnosing mediastinal metastases (N2 disease) and the number needed to treat (NNT: number of patients needed to undergo EBUS-TBNA to avoid a case of pathologic N2 disease after resection) were calculated. RESULTS: One-hundred eighteen patients were included. EBUS-TBNA proved N2 disease in four patients. In the remaining 114 patients who underwent mediastinoscopy, VAMLA and/or resection there were two cases of N2 (N2 prevalence 5.1%). The sensitivity, specificity, NPV, PPV and overall accuracy for diagnosing mediastinal metastases (N2 disease) were of 66%, 100%, 98%, 100% and 98%, respectively. The NNT was 31 (95% CI: 15-119). CONCLUSION: EBUS-TBNA in patients with central clinically staged T1N0M0 NSCLC presents a good diagnostic accuracy for mediastinal staging, even in a population with low prevalence of N2 disease. Therefore, its indication should be considered in the management of even these early lung cancers.

Pathological N1/N2 in Clinical Stage I Bronchogenic Carcinoma. Analysis From a Prospective Multicentre Database.

OBJECTIVES: To determine the incidence of occult N1/N2 nodal metastases and associated risk factors in patients with non-small cell lung cancer no larger than 3cm and deemed cN0 by CT and PET-CT in a prospective, multicentre national database. METHODS: Patients with a NSCLC no larger than 3cm, deemed cN0 by PET-CT and CT scan, who had undergone at least a lobectomy, were selected from a national multicentre database of 3533 patients who had undergone anatomic lung resection between 2016 and 2018. Clinical and pathological variables of patients with pN0 and patients with pN1/N2 were compared to identify factors associated with the presence of lymph node metastases. Chi2 and the Mann-Whitney U test were used for categorical and numerical variables, respectively. All variables with p<0.2 in the univariate analysis were included in the multivariate logistic regression analysis. RESULTS: The study included 1205 patients from the cohort. The incidence of occult pN1/N2 disease was 10.70% (95%CI, 9.01-12.58). The multivariable analysis revealed that the degree of differentiation, size, location (central or peripheral) and SUV of the tumour in PET, surgeon experience and number of lymph nodes resected were associated with occult N1/N2 metastases. CONCLUSIONS: The incidence of occult N1/N2 in patients with bronchogenic carcinoma with cN0 tumours no larger than 3cm is no negligible. Data about the degree of differentiation, tumour size in CT scan, maximal uptake of the tumour in PET-CT, location (central or peripheral), number of lymph nodes resected and surgeon seniority is relevant in order to detect patients at risk.

External validation of the European Society of Thoracic Surgeons morbidity and mortality risk models.

OBJECTIVES: There is a wide variety of predictive models of postoperative risk, although some of them are specific to thoracic surgery, none of them is widely used. The European Society for Thoracic Surgery has recently updated its models of cardiopulmonary morbidity (Eurolung 1) and 30-day mortality (Eurolung 2) after anatomic lung resection. The aim of our work is to carry out the external validation of both models in a multicentre national database. METHODS: External validation of Eurolung 1 and Eurolung 2 was evaluated through calibration (calibration plot, Brier score and Hosmer-Lemeshow test) and discrimination [area under receiver operating characteristic curves (AUC ROC)], on a national multicentre database of 2858 patients undergoing anatomic lung resection between 2016 and 2018. RESULTS: For Eurolung 1, calibration plot showed suboptimal overlapping (slope = 0.921) and a Hosmer-Lemeshow test and Brier score of P = 0.353 and 0.104, respectively. In terms of discrimination, AUC ROC for Eurolung 1 was 0.653 (95% confidence interval, 0.623-0.684). In contrast, Eurolung 2 showed a good calibration (slope = 1.038) and a Hosmer-Lemeshow test and Brier score of P = 0.234 and 0.020, respectively. AUC ROC for Eurolung 2 was 0.760 (95% confidence interval, 0.701-0.819). CONCLUSIONS: Thirty-day mortality score (Eurolung 2) seems to be transportable to other anatomic lung-resected patients. On the other hand, postoperative cardiopulmonary morbidity score (Eurolung 1) seems not to have sufficient generalizability for new patients.

Treatment and intention-to-treat propensity score analysis to evaluate the impact of video-assisted thoracic surgery on 90-day mortality after anatomical resection for lung cancer.

OBJECTIVES: The aim of this study was to know the treatment effect of video-assisted thoracic surgery (VATS) on 90-day mortality after anatomical lung resection based on a nationwide cohort. METHODS: This is a multicentre prospective cohort of 2721 anatomical resections for lung cancer from December 2016 to March 2018. Treatment and intention-to-treat (ITT) analyses were performed after inverse probability score weighting and different propensity score matching algorithms. Covariate balance was assessed by standardized mean differences. The estimators reported were the average treatment effect, the average treatment effect on the treated and odds ratios after conditional logistic models with 95% confidence intervals. The unconfoundedness assumption was evaluated by sensitivity analysis for average treatment effect (c-dependence) and average treatment effect on the treated (Γ). RESULTS: VATS was the initial approach in 1911 patients (70.2%), though 273 cases (14.3%) had to be converted to thoracotomy. Ninety-day mortality rates were: treatment analysis (VATS 1.16% vs open 3.9%, P < 0.001), ITT analysis (VATS 1.78% vs open 3.36%, P = 0.012). After inverse probability score weighting and propensity score matching, in the treatment analysis, VATS meant absolute risk reductions between 2.25% and 2.96% and relative risk reductions between 65% and 70% [OR = 0.34 (95% confidence interval 0.15-0.79), all P-values <0.004). However, all the estimators turned out to be non-significant in the ITT analyses. A high sensitivity to unobservable confounders was proved (c-dependence 0.135, Γ = 1.5). CONCLUSIONS: VATS can reduce the risk of 90-day mortality after anatomical lung resection. However, the implications of conversion to thoracotomy, comparing ITT versus treatment analysis, and the potential impact of hidden bias should deserve further attention in the future.

Radicality of lymphadenectomy in lung cancer resections by thoracotomy and video-assisted thoracoscopic approach: A prospective, multicentre and propensity-score adjusted study.

OBJECTIVE: To analyse differences in intraoperative nodal assessment in patients undergoing lung cancer resection by thoracotomy and video-assisted thoracoscopy (VATS) in the Spanish Video-Assisted Thoracic Surgery Group (GEVATS). METHODS: Prospective multicentre cohort study of anatomic pulmonary resections (n = 3533) performed from December 2016 to March 2018. Main surgical, clinical and oncological variables related with lymphadenectomy were compared according to surgical approach. Corresponding tests for homogeneity were performed. Multiple logistic regression analyses were used to determine the odds ratio (OR) and 95% confidence interval (95%CI). Covariate adjustment using the propensity score (PS) was performed to reduce confounding effects. RESULTS: After exclusions, 2532 patients were analysed. Systematic nodal dissection (SND) was performed in 65%, with a median of resected/sampled lymph nodes (LN) of 7 (IQR 4-12) and pathologic (p) N2 and uncertain (u) pNu rates of 9.4% and 28.9%, respectively. At multivariate analysis, the following were associated with thoracotomy (OR; 95%CI): SND (1.4; 1.08-1.96; p = 0.014), staging mediastinoscopy (2.6; 1.59-4.25; p < 0.001), tumor > 3 cm (2.1; 1.66-2.78; p < 0.001), central tumor (2.5; 1.90-3.24; p < 0.001); pN1 (1.8; 1.25-2.67; p < 0.002), pN2 (1.8; 1.18-2.76; p = 0.006), lower FEV1 (0.9; 0.98-0.99; p < 0.001), squamous cell carcinoma (1.5; 1.16-1.98; p = 0.002) and inexperienced surgeons in VATS (compared with > 100 VATS experience) (37.6; 13.55-104.6; p < 0.001). After PS adjustment, SND maintained the OR, but in the limit of signification (1.4; 1-1.98; p = 0.05). Nodal upstaging was significantly higher in the thoracotomy group. Complication rates of SND and no SND were similar. CONCLUSIONS: Thoracotomy was associated with a more thorough lymphadenectomy in GEVATS. Therefore, intraoperative lymph node evaluation performed at VATS should be improved to have better prognostic information and more solid grounds to indicate adjuvant therapy.

Surgical Risk Following Anatomic Lung Resection in Thoracic Surgery: A Prediction Model Derived from a Spanish Multicenter Database. / Riesgo quirúrgico tras resección pulmonar anatómica en cirugía torácica. Modelo predictivo a partir de una base de datos nacional multicéntrica.

INTRODUCTION: The aim of this study was to develop a surgical risk prediction model in patients undergoing anatomic lung resections from the registry of the Spanish Video-Assisted Thoracic Surgery Group (GEVATS). METHODS: Data were collected from 3,533 patients undergoing anatomic lung resection for any diagnosis between December 20, 2016 and March 20, 2018. We defined a combined outcome variable: death or Clavien Dindo grade IV complication at 90 days after surgery. Univariate and multivariate analyses were performed by logistic regression. Internal validation of the model was performed using resampling techniques. RESULTS: The incidence of the outcome variable was 4.29% (95% CI 3.6-4.9). The variables remaining in the final logistic model were: age, sex, previous lung cancer resection, dyspnea (mMRC), right pneumonectomy, and ppo DLCO. The performance parameters of the model adjusted by resampling were: C-statistic 0.712 (95% CI 0.648-0.750), Brier score 0.042 and bootstrap shrinkage 0.854. CONCLUSIONS: The risk prediction model obtained from the GEVATS database is a simple, valid, and reliable model that is a useful tool for establishing the risk of a patient undergoing anatomic lung resection.

Effect of COVID-19 on Thoracic Oncology Surgery in Spain: A Spanish Thoracic Surgery Society (SECT) Survey.

After the first wave of COVID-19, the Spanish Society of Thoracic Surgeons (SECT) surveyed its members to assess the impact of the pandemic on thoracic oncology surgery in Spain. In May 2020, all SECT members were invited to complete an online, 40-item, multiple choice questionnaire. The questionnaire was developed by the SECT Scientific Committee and sent via email. The overall response rate was 19.2%. The respondents answered at least 91.5% of the items, with only one exception (a question about residents). Most respondents (89.3%) worked in public hospitals. The reported impact of the pandemic on routine clinical activity was considered extreme or severe by 75.5% of respondents (25.5% and 50%, respectively). Multidisciplinary tumour boards were held either with fewer members attending or through electronic platforms (44.6% and 35.9%, respectively). Surgical activity decreased by 95.7%, with 41.5% of centers performing surgery only on oncological patients and 11.7% only in emergencies. Nearly 60% of respondents reported modifying standard protocols for early-stage cancer and in the preoperative workup. Most centers (≈80%) reported using full personal protective equipment when operating on COVID-19 positive patients. The COVID-19 pandemic severely affected thoracic oncology surgery in Spain. The lack of common protocols led to a variable care delivery to lung cancer patients.

How do we Classify a Central Tumor? Results of a Multidisciplinary Survey from the SEPAR Thoracic Oncology Area. / ¿Cómo clasificamos un tumor central? Resultados de una encuesta multidisciplinaria propuesta desde el área de Oncología Torácica de SEPAR.

INTRODUCTION: In patients with non-small cell lung cancer (NSCLC) and normal mediastinal imaging tests, centrally located tumors have greater occult mediastinal involvement. Clinical guidelines, therefore, recommend invasive mediastinal staging in this situation. However, definitions of centrality in the different guidelines are inconsistent. The SEPAR Thoracic Oncology area aimed to evaluate the degree of familiarity with various concepts related to tumor site among professionals who see patients with NSCLC in Spain. METHODS: A questionnaire was distributed to members of Spanish medical societies involved in the management of NSCLC, structured according to the 3 aspects to be evaluated: 1) uniformity in the definition of central tumor location; 2) uniformity in the classification of lesions that extend beyond dividing lines; and 3) ability to delineate lesions in the absence of dividing lines. RESULTS: A total of 430 participants responded. The most voted definition of centrality was «lesions in contact with hilar structures¼ (49.7%). The lines most often chosen to delimit the hemitorax were concentric hilar lines (89%). Most participants (92.8%) classified tumors according to the side of the dividing line that contained most of their volume. Overall, 78.6% were able to correctly classify a central lesion in the absence of dividing lines. CONCLUSIONS: In our survey, the most widely accepted definition of centrality is not one of the proposals specified in the clinical guidelines. The results reflect wide variability in the classification of tumor lesions.

Geometrical Measurement of Central Tumor Location in cT1N0M0 NSCLC Predicts N1 but Not N2 Upstaging.

BACKGROUND: In patients with non-small cell lung cancer (NSCLC) and normal mediastinum, the central tumor location predicts occult nodal disease (both N1 and N2). We evaluated a novel definition of central location based on a geometrical measurement of the tumor location within the lung that could predict N2, N1, or both. METHODS: This retrospective study included patients with confirmed NSCLC, radiologically and metabolically staged T1 N0 M0, who underwent invasive mediastinal staging and/or lung resection. The central tumor location was measured considering 2 ratios. The inner margin ratio (IMR) and outer margin ratio (OMR) were both calculated as the distance from the inner margin of the lung to both margins of the tumor (inner [IMR], outer [OMR]) divided by the lung width. Optimal cutoffs for IMR and OMR were calculated. Tumors with values lower than the cutoffs were considered central. Prevalences of N1 and N2 upstaging were estimated and bivariate logistic regression analysis was performed to predict the odds of N1 and N2 upstaging using IMR and OMR cutoffs. RESULTS: A total of 209 patients were included. The prevalence of N1 and N2 upstaging was 11% and 5.3%, respectively. Cutoffs of 0.5 for IMR and 0.64 for OMR were estimated. Both ratios predicted N1 upstaging (adjusted odds ratio [95% confidence interval]: 4.2 [1.5-12]; P < .007; area under the curve, 0.65) but did not predict N2 upstaging. CONCLUSIONS: Central tumor location can be assessed by means of IMR and OMR and predicts N1 upstaging in patients with radiologically and metabolically T1 N0 M0 tumors. This is important for the selection of patients for therapies that require N0 tumors.

Recommendations for acting in elective and urgent thoracic surgery during SARS-CoV-2 pandemic. Spanish Society of Thoracic Surgery. / Recomendaciones de actuación en cirugía torácica electiva y urgente en contexto de pandemia por SARS-CoV-2 de la Sociedad Española de Cirugía Torácica (SECT).

Expansion of the pandemic produced by new coronavirus SATS-CoV-2 has made healthcare focused on patients with COVID-19 disease, leading to discontinue most of elective surgical procedures. Being thoracic surgery eminently oncological, an optimal triage of patients amenable to be safely operated on is mandatory. Moreover, severe pulmonary involvement by COVID-19 causes complications frequently needing urgent thoracic surgical procedures under a new context. The Spanish Society of Thoracic Surgery (SECT) has developed this document to establish basic recommendations to keep up essential elective surgical activity and to guide surgeons facing thoracic urgencies in this new and unknown environment.

Preoperative staging of the mediastinum is an essential and multidisciplinary task.

Mediastinal staging is a crucial step in the management of patients with NSCLC. With the recent development of novel techniques, mediastinal staging has evolved from an activity of interest mainly for thoracic surgeons to a joint effort carried out by many specialists. In this regard, the debate of cases in MDT sessions is crucial for optimal management of patients. Current evidence-based clinical guidelines for preoperative NSCLC staging recommend that mediastinal staging should be performed with increasing invasiveness. Image-based techniques are the first approach, although they have limited accuracy and findings must be confirmed by pathology in almost all cases. In this setting, the advent of radiomics is promising. Invasive staging depends on procedural factors rather than diagnostic performance. The choice between endoscopy-based or surgical procedures should depend on the local expertise of each centre. As the extension of mediastinal disease in terms of number of involved lymph nodes and nodal stations affects prognosis and the choice of treatment, systematic samplings are preferred over random targeted samplings. Following this approach, a diagnosis of single mediastinal nodal involvement can be unreliable if all reachable mediastinal nodal stations have not been assessed. The performance of confirmatory mediastinoscopy after a negative endoscopy-based procedure is controversial but currently recommended. Current indications of invasive staging in patients with radiologically normal mediastinum have to be re-evaluated, especially for central tumour location.

Spanish Video-Assisted Thoracic Surgery Group: Method, Auditing, and Initial Results From a National Prospective Cohort of Patients Receiving Anatomical Lung Resections.

INTRODUCTION: Our study sought to know the current implementation of video-assisted thoracoscopic surgery (VATS) for anatomical lung resections in Spain. We present our initial results and describe the auditing systems developed by the Spanish VATS Group (GEVATS). METHODS: We conducted a prospective multicentre cohort study that included patients receiving anatomical lung resections between 12/20/2016 and 03/20/2018. The main quality controls consisted of determining the recruitment rate of each centre and the accuracy of the perioperative data collected based on six key variables. The implications of a low recruitment rate were analysed for "90-day mortality" and "Grade IIIb-V complications". RESULTS: The series was composed of 3533 cases (1917 VATS; 54.3%) across 33 departments. The centres' median recruitment rate was 99% (25-75th:76-100%), with an overall recruitment rate of 83% and a data accuracy of 98%. We were unable to demonstrate a significant association between the recruitment rate and the risk of morbidity/mortality, but a trend was found in the unadjusted analysis for those centres with recruitment rates lower than 80% (centres with 95-100% rates as reference): grade IIIb-V OR=0.61 (p=0.081), 90-day mortality OR=0.46 (p=0.051). CONCLUSIONS: More than half of the anatomical lung resections in Spain are performed via VATS. According to our results, the centre's recruitment rate and its potential implications due to selection bias, should deserve further attention by the main voluntary multicentre studies of our speciality. The high representativeness as well as the reliability of the GEVATS data constitute a fundamental point of departure for this nationwide cohort.

Src-Homology 2 Domain-Containing Phosphatase 2 in Resected EGFR Mutation-Positive Lung Adenocarcinoma.

INTRODUCTION: EGFR mutation-positive lung adenocarcinoma (LUAD) displays impaired phosphorylation of ERK and Src-homology 2 domain-containing phosphatase 2 (SHP2) in comparison with EGFR wild-type LUADs. We hypothesize that SHP2 expression could be predictive in patients positive with resected EGFR mutation versus patients with EGFR wild-type LUAD. METHODS: We examined resected LUAD cases from Japan and Spain. mRNA expression levels of AXL, MET, CDCP1, STAT3, YAP1, and SHP2 were analyzed by quantitative reverse transcriptase polymerase chain reaction. The activity of SHP2 inhibitors plus erlotinib were tested in EGFR-mutant cell lines and analyzed by cell viability assay, Western blot, and immunofluorescence. RESULTS: A total of 50 of 100 EGFR mutation-positive LUADs relapsed, among them, patients with higher SHP2 mRNA expression revealed shorter progression-free survival, in comparison with those having low SHP2 mRNA (hazard ratio: 1.83; 95% confidence interval: 1.05-3.23; p = 0.0329). However, SHP2 was not associated with prognosis in the remaining 167 patients with wild-type EGFR. In EGFR-mutant cell lines, the combination of SHP099 or RMC-4550 (SHP2 inhibitors) with erlotinib revealed synergism via abrogation of phosphorylated AKT (S473) and ERK1/2 (T202/Y204). Although erlotinib translocates phosphorylated SHP2 (Y542) into the nucleus, either RMC-4550 alone, or in combination with erlotinib, relocates SHP2 into the cytoplasm membrane, limiting AKT and ERK1/2 activation. CONCLUSIONS: Elevated SHP2 mRNA levels are associated with recurrence in resected EGFR mutation-positive LUADs, but not in EGFR wild-type. EGFR tyrosine kinase inhibitors can enhance SHP2 activation, hindering adjuvant therapy. SHP2 inhibitors could improve the benefit of adjuvant therapy in EGFR mutation-positive LUADs.

Nodal size ranking as a predictor of mediastinal involvement in clinical early-stage non-small cell lung cancer.

In non-small cell lung cancer (NSCLC) patients, the recommended minimum requirement for an endoscopy-based mediastinal staging procedure is sampling the largest lymph node (LN) in right and left inferior paratracheal, and subcarinal stations. We aimed to analyze the percentage of cases where the largest LN in each mediastinal station was malignant in a cohort of NSCLC patients with mediastinal metastases diagnosed in the lymphadenectomy specimen. Furthermore, we investigated the sensitivity of a preoperative staging procedure in a hypothetical scenario where only the largest LN of each station would have been sampled.Prospective data of patients with mediastinal nodal metastases diagnosed in the lymphadenectomy specimens were retrospectively analyzed. The long-axis diameter of the maximal cut surface of all LNs was measured on hematoxylin and eosin-stained sections.Seven hundred seventy five patients underwent operation and 49 (6%) with mediastinal nodal disease were included. A total of 713 LNs were resected and 119 were involved. Sixty seven nodal stations revealed malignant LNs: in these, the largest LN was malignant in 39 (58%). In a "per patient" analysis, a preoperative staging procedure that sampled only the largest LN would have attained a sensitivity of 0.67; and if the largest and the second largest were sampled, sensitivity would be 0.87.In patients with NSCLC, nodal size ranking is not reliable enough to predict malignancy. In clinical practice, regardless of the preoperative staging method, systematic thorough sampling of all visible LNs is to be recommended over selective random samplings.

Cervical mediastinoscopy and video-assisted mediastinoscopic lymphadenectomy for the staging of non-small cell lung cancer.

The staging of mediastinal lymph nodes is essential for planning the most adequate treatment for patients with non-small cell lung cancer (NSCLC). For this reason, the current American and European guidelines recommend obtaining tissue confirmation of any mediastinal abnormality seen on chest computed tomography (CT) and positron emission tomography (PET). This can be done by endoscopic techniques, such as endobronchial ultrasonographic fine-needle aspiration (EBUS-FNA), esophageal ultrasonographic FNA (EUS-FNA), or a combination of the two (CUS). Traditionally, surgical methods have been reserved to validate the negative results of minimally invasive endoscopic techniques. However, based on the latest evidence, cervical mediastinoscopy and video-assisted mediastinoscopic lymphadenectomy (VAMLA) have demonstrated their superiority over minimally invasive methods in terms of performance for those tumors with normal mediastinum [clinical (c) N0-1 by CT and PET]. Therefore, cervical mediastinoscopy and VAMLA should be considered in the staging algorithms of this particular subset of NSCLC, and in the other well-established indications.