Invasive Mediastinal Staging Research Articles

What Does N2 Lymph Node Involvement Mean for Patients with Non-Small Cell Lung Cancer (NSCLC)?-A Review of Implications for Diagnosis and Treatment.

Patients with stage III NSCLC with N2 lymph node involvement carry a complex and diverse disease entity. Challenges persist in the areas of diagnosis, staging, multimodal management, and the determination of surgical indications and resectability criteria. Therefore, this review focuses on the latest updates in N2 disease staging and its prognostic and treatment implications. Emphasis is placed on the importance of accurate staging using imaging modalities such as [18F]FDG-PET/CT as well as minimally invasive mediastinal staging endoscopic techniques. The evolving role of surgery in the management of N2 disease is also explored. The benefits of neoadjuvant and adjuvant treatments have been demonstrated, along with the efficacy of a combined multimodal approach with chemo-immunotherapy in the perioperative setting, reigniting the debate of N2 disease subsets and optimal treatment options. Furthermore, this review addresses the controversies surrounding surgical approaches in upfront "borderline" resectable stage III NSCLC as well as the benefits of combined chemoradiotherapy with consolidation immunotherapy for patients with unresectable tumors. In conclusion, personalized diagnostic and treatment approaches tailored to individual patient characteristics, resource availability, and institutional expertise are essential for optimizing outcomes in patients with stage III-N2 NSCLC.

Minimally Invasive with Maximal Yield: A Narrative Review of Current Practices in Mediastinal Lymph Node Staging in Non-Small Cell Lung Cancer.

Background: Lung cancer remains the leading cause of cancer deaths in the United States despite declining incidence and improved outcomes because of advancements in early detection and development of novel therapies. Accurate mediastinal lymph node staging is crucial for determining prognosis and guiding treatment decisions, particularly for non-small cell lung cancer (NSCLC). Materials and Methods: A systematic search of PubMed was conducted to identify English language articles published between January 2010 and January 2024 focusing on preoperative lymph node staging in adults with NSCLC. Case series, observational studies, randomized trials, guidelines, narrative reviews, systematic reviews, and meta-analyses were included. Results: Various imaging modalities, surgical and nonsurgical procedures for mediastinal lymph node staging were reviewed, including positron emission tomography with computed tomography, cervical mediastinoscopy, video-assisted cervical mediastinoscopy, anterior mediastinotomy, video-assisted thoracoscopy, endobronchial ultrasound-guided fine needle aspiration (EBUS-FNA), transesophageal endoscopic ultrasound-guided fine needle aspiration (EUS-FNA), and computed tomography-guided percutaneous lymph node biopsy. EBUS-FNA emerged as the preferred initial staging procedure because of its high sensitivity and low complication rate. Combining it with other procedures or confirmatory testing may be helpful in determining appropriate treatment. Conclusions: Although cervical mediastinoscopy remains a valuable confirmatory procedure in select cases, its role as a first-line staging modality is diminishing with the widespread adoption of EBUS-FNA and EUS-FNA. The combination of EBUS-FNA and EUS-FNA allows access to nearly all mediastinal lymph node stations with high diagnostic accuracy. Future research may further refine the selection criteria for invasive mediastinal staging procedures, ultimately optimizing patient outcomes in the management of NSCLC.

Presurgical invasive mediastinal staging in lung cancer, unexpected N2 and long-term survival: a registry-based study with data from the Spanish group for video-assisted thoracic surgery.

Mediastinal lymph node staging is a key element in the diagnosis of lung cancer. The combination of computed tomography (CT) and positron emission tomography (PET) has improved staging but some circumstances are known to influence their negative predictive value. The objective of this study was to assess the impact on survival of avoiding invasive mediastinal staging in surgical lung cancer patients with negative mediastinum in CT and PET and intermediate risk of unexpected pN2. Data were collected from the prospective cohort of the Spanish Group for Video-Assisted Thoracic Surgery (GEVATS), from December 2016 to March 2018. For this study, patients were selected if they had negative mediastinum in CT and PET findings but tumours >3 cm or located centrally, or with cN1 disease. Patients who did and did not undergo invasive staging [invasive group (IG) and non-invasive group (NIG)] were compared, analysing unexpected pN2 and survival with Kaplan-Meier curves and Cox regression. A total of 2,826 patients underwent surgery for primary lung cancer. We selected 1,247 patients who had tumours >3 cm, central tumours or cN1. Invasive staging was performed in 275 (22.1%) cases. The unexpected pN2 rate was 9.6% in the NIG and 13.8% in the IG, but half of them were discovered prior to surgery in the IG. Five-year overall survival (OS) was poorer in the IG (52.4% vs. 64%; P<0.001). In the Cox regression model, male sex, older age, diabetes, synchronous tumour, lower diffusing capacity for carbon monoxide, larger tumour size, higher pathological N-stage, and IG status were significant independent risk factors. Invasive staging recommended by guidelines could be reduced with an appropriate selection in mediastinal CT- and PET-negative patients with risk factors for unexpected pN2, because rates of pN2 and survival did not worsen without invasive staging.

Role of EBUS-TBNA in Mediastinal Staging of NSCLC Patients

Abstract Purpose Mediastinal staging in non-small-cell lung carcinoma (NSCLC) is essential for appropriate treatment. Invasive mediastinal staging is necessary and mediastinoscopy has been the gold standard, but it is associated with morbidity. The aim of this study is to evaluate the efficacy of endobronchial ultrasonography transbronchial needle aspiration (EBUS-TBNA), compare it with mediastinoscopy, and assess the endosonographic features of lymph nodes for prediction of metastasis. Methods This is a retrospective study of 200 patients with NSCLC who underwent EBUS-TBNA from January 2017 to December 2019. The patients with potentially resectable NSCLC who underwent EBUS-TBNA were included. Standard definitions of sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and diagnostic accuracy were used to determine the diagnostic performance of EBUS-TBNA. Results A total of 200 patients and 616 nodes were studied, out of which 515 were benign and 101 were malignant. Out of 200 cases, 129 (64.5%) had &lt;N2 disease, 59 (29.5%) had N2 disease, and 12 (6%) had N3 disease. EBUS-TBNA had a sensitivity of 78.87%, specificity of 96.12%, NPV of 89.2%, PPV of 91.8%, and accuracy of 90%. Ultrasonography (USG) features of 297 nodes were available and statistical significance was seen in rounded shape, size greater than 10 mm, ill-defined nodal margins, absence of hilum, and hypoechoic echotexture (p &lt; 0.05). Conclusion EBUS-TBNA is a safe and efficacious procedure for mediastinal sampling of NSCLC patients. Familiarity with endosonographic features of lymph nodes, which can predict malignancy in nodes, may further improve the yield of EBUS-TBNA and reduce under-staging.

Role of invasive mediastinal nodal staging in survival outcomes of patients with non-small cell lung cancer and without radiologic lymph node metastasis: a retrospective cohort study

Lung cancer diagnostic guidelines advocate for invasive mediastinal nodal staging (IMNS), but the survival benefits of this approach in patients with non-small cell lung cancer (NSCLC) without radiologic evidence of lymph node metastasis (rN0) remain uncertain. We aimed to investigate the impact of IMNS in patients with rN0 NSCLC by comparing the long-term survival between patients who underwent IMNS and those who did not (non-IMNS). In this retrospective cohort study, we included patients with NSCLC but without radiologic evidence of lymph node metastasis from the Registry for Thoracic Cancer Surgery and the clinical data warehouse at the Samsung Medical Centre, Republic of Korea between January 2, 2008 and December 31, 2016. We compared the 5-year overall survival (OS) rate as the primary outcome after propensity score matching between the IMNS and non-IMNS groups. The age, sex, performance statue, tumor size, centrality, solidity, lung function, FDG uptake in PET-CT, and histological examination of the tumor before surgery were matched. A total of 4545 patients (887 in the IMNS group and 3658 in the non-IMNS group) who received curative treatment for NSCLC were included in this study. By the mediastinal node dissection, the overall incidence of unforeseen mediastinal node metastasis (N2) was 7.2% (317/4378 patients). Despite the IMNS, 67% of pathological N2 was missed (61/91 patients with unforeseen N2). Based on propensity score matching, 866 patients each for the IMNS and non-IMNS groups were assigned. There was no significant difference in 5-year OS and recurrence-free survival (RFS) between two groups: 5-year OS was 73.9% (95% confidence interval, CI: 71%-77%) for IMNS and 71.7% (95% CI: 68.6%-74.9%; p=0.23), for non-IMNS (hazard ratio, HR 0.90, 95% CI: 0.77-1.07), while 5-year RFS was 64.7% (95% CI: 61.5%-68.2%) and 67.5% (95% CI: 64.3%-70.9%; p=0.35 (HR 1.08, 95% CI: 0.92-1.27), respectively. Moreover, the timing and locations of recurrence were similar in both groups. IMNS might not be required before surgery for patients with NSCLC without LN suspicious of metastasis. Further randomised trials are required to validate the findings of the present study. None.

Accuracy of nodal staging by 18F-FDG-PET/CT in limited disease small-cell lung cancer.

Small-cell lung cancer (SCLC) is highly aggressive with a nearly incurable disease in most cases. The most important prognostic factor is the status of the mediastinal lymph nodes. Only a small proportion of patients can be diagnosed at early stages and directed to curative multimodal treatment. Therefore, accuracy of nodal staging by (18F)-Fluoro-2-deoxyglucose (FDG) positron emission tomography (PET) computed tomography (18F-FDG-PET/CT) in (very) limited disease SCLC, although not well investigated, is highly important. Treatment naive, non-bulky patients treated or diagnosed with SCLC between June 2012 and April 2020 with complete data including FDG-PET/CT and invasive mediastinal staging were retrospectively analyzed (n = 19). Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV) and accuracy of mediastinal lymph node staging of 18F-FDG-PET/CT was calculated. The FDG-PET/CT showed a sensitivity of 91%, and the specificity was calculated as 87.5%. In this cohort, the disease prevalence in lymph nodes was 58% (n = 11). Positive predictive value was 91%, NPV 88% and accuracy calculated at 89%. One patient was upstaged from single-level N2 to multilevel N2. In one patient, upstaging in invasive staging was performed from N2 to N3, and one patient was downstaged from N1 to N0. FDG-PET/CT is a valuable tool for the detection of distant metastases, but in mediastinal staging of SCLC some limitations might remain. Invasive methods remain the gold standard. Therefore, the mediastinal lymph nodal status of patients with SCLC screened for multimodal treatment should be further evaluated by additional invasive techniques to verify the exact N-staging and to optimize treatment stratification.

Assessing current diagnostic, staging, and treatment practices in community and academic centers for individuals with stage IB-IIIA non–small-cell lung cancer (NSCLC).

e20608 Background: The five-year survival for individuals with surgically resected, early-stage NSCLC is around 50%. Recent availability of biomarker driven therapy after surgery has the promise of improved outcomes. However, deficits in the quality of diagnostic evaluation, evidence-based treatment delivery, care coordination, and biomarker testing are still barriers to optimal outcomes. Methods: In 2022, the Association of Community Cancer Centers (ACCC) conducted a survey of NSCLC providers to assess current patterns in the diagnosis and treatment of patients with early-stage (IB-IIIA) NSCLC. The survey, which was distributed to ACCC members and their associated networks, collected information about each respondent and their cancer program processes around diagnosis, treatment planning, and care delivery. We administered it Qualtrics and analyzed results with SAS 9.4. Results: We had 124 survey respondents from 33 US states. Respondents’ institutions were 60% urban, 23% suburban, and 17% rural, 53% community cancer programs, 37% academic/NCI designated cancer programs, 9% private practice. On average, initial tissue biopsy was performed by interventional radiologists in 29% of cases, interventional pulmonologist in 22%, and thoracic surgeons in 16%. In stage IIA-IIIA, on average 49% typically perform invasive mediastinal staging before surgery, 17% during surgery, and 18% do not typically perform invasive mediastinal staging. The most frequent barriers to optimal staging and diagnosis included scheduling (73%), cost (51%), tissue quality (46%), limited access to tests or procedures (42%), and missed appointments (36%). Multidisciplinary tumor board use included 31% with a general cancer tumor board, 50% with a thoracic specific tumor board, and 14% have a dedicated molecular tumor board. Tumor board meetings were weekly in 57%, 2-3 times a month in 22%, and once a month in 11%. 66% have a standard biomarker testing protocol for resected NSCLC. 51% typically order EGFR and 31% regularly order PDL1 testing for patients with resected NSCLC. The largest barriers to optimal care included: scheduling (23%), patient refusal (19%), communication breakdowns (17%), inadequate staffing (15%), and limited access to subspecialties (14%). 83% agree their center has the staff and resources to help patients navigating the health system. However, only 45% typically assign a nurse navigator to individuals with early-stage NSCLC. Palliative care service referrals were made sometimes or often in 48% of sites, while 51% refer rarely or never. Conclusions: In this broad sample of oncology practices across the US, we identified several strengths and barriers to optimal care for persons with early-stage NSCLC. Improved care coordination and standardized staging and diagnosis practices could optimize care in this dynamic treatment landscape.

Prediction Models for Mediastinal Metastasis and Its Detection by Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration in Potentially Operable Non-Small Cell Lung Cancer: A Prospective Study

Prediction models for mediastinal metastasis and its detection by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) have not been developed using a prospective cohort of potentially operable patients with non-small cell lung cancer (NSCLC). Can mediastinal metastasis and its detection by EBUS-TBNA be predicted with prediction models in NSCLC? For the prospective development cohort, 589 potentially operable patients with NSCLC were evaluated (July 2016-June 2019) from five Korean teaching hospitals. Mediastinal staging was performed using EBUS-TBNA (with or without the transesophageal approach). Surgery was performed for patients without clinical N (cN) 2-3 disease by endoscopic staging. The prediction model for lung cancer staging-mediastinal metastasis (PLUS-M) and a model for mediastinal metastasis detection by EBUS-TBNA (PLUS-E) were developed using multivariable logistic regression analyses. Validation was performed using a retrospective cohort (n= 309) from a different period (June 2019-August 2021). The prevalence of mediastinal metastasis diagnosed by EBUS-TBNA or surgery and the sensitivity of EBUS-TBNA in the development cohort were 35.3%and 87.0%, respectively. In PLUS-M, younger age (< 60 years and 60-70 years compared with≥ 70 years), nonsquamous histology (adenocarcinoma and others), central tumor location, tumor size (> 3-5cm), cN1 or cN2-3 stage by CT, and cN1 or cN2-3 stage by PET-CT were significant risk factors for N2-3 disease. Areas under the receiver operating characteristic curve (AUCs) for PLUS-M and PLUS-E were 0.876 (95%CI, 0.845-0.906) and 0.889 (95%CI, 0.859-0.918), respectively. Model fit was good (PLUS-M: Hosmer-Lemeshow P= .658, Brier score= 0.129; PLUS-E: Hosmer-Lemeshow P= .569, Brier score= 0.118). In the validation cohort, PLUS-M (AUC, 0.859 [95%CI, 0.817-0.902], Hosmer-Lemeshow P= .609, Brier score= 0.144) and PLUS-E (AUC, 0.900 [95%CI, 0.865-0.936], Hosmer-Lemeshow P= .361, Brier score= 0.112) showed good discrimination ability and calibration. PLUS-M and PLUS-E can be used effectively for decision-making for invasive mediastinal staging in NSCLC. ClinicalTrials.gov; No.: NCT02991924; URL: www. gov.

Rate and Predictors of Unforeseen PN1/PN2-Disease in Surgically Treated cN0 NSCLC-Patients with Primary Tumor > 3 cm: Nationwide Results from Italian VATS-Group Database.

Background. Since no robust data are available on the real rate of unforeseen N1-N2 disease (uN) and the relative predictive factors in clinical-N0 NSCLC with peripheral tumours > 3 cm, the usefulness of performing a (mini)invasive mediastinal staging in this setting is debated. Herein, we investigated these issues in a nationwide database. Methods. From 01/2014 to 06/2020, 15,784 thoracoscopic major lung resections were prospectively recorded in the "Italian VATS-Group" database. Among them, 1982 clinical-N0 peripheral solid-type NSCLC > 3 cm were identified, and information was retrospectively reviewed. A mean comparison of more than two groups was made by ANOVA (Bonferroni correction for multiple comparisons), while associations between the categorical variables were estimated with a Chi-square test. The multivariate logistic regression model and Kaplan-Meyer method were used to identify the independent predictors of nodal upstaging and survival results, respectively. Results. At pathological staging, 229 patients had N1-involvement (11.6%), and 169 had uN2 disease (8.5%). Independent predictors of uN1 were SUVmax (OR: 1.98; CI 95: 1.44-2.73, p = 0.0001) and tumour-size (OR: 1.52; CI: 1.11-2.10, p = 0.01), while independent predictors of uN2 were age (OR: 0.98; CI 95: 0.96-0.99, p = 0.039), histology (OR: 0.48; CI 95: 0.30-0.78, p = 0.003), SUVmax (OR: 2.07; CI 95: 1.15-3.72, p = 0.015), and the number of resected lymph nodes (OR: 1.03; CI 95: 1.01-1.05, p = 0.002). Conclusions. The unforeseen N1-N2 disease in cN0/NSCLCs > 3 cm undergoing VATS resection is observable in between 12 and 8% of all cases. We have identified predictors that could guide physicians in selecting the best candidate for (mini)invasive mediastinal staging.

Diagnostic Performance of Endosonography to Detect Mediastinal Lymph Node Metastasis in Patients with Radiological N1 Non-Small Cell Lung Cancer.

Guidelines recommend that non-small cell lung cancer (NSCLC) patients with suspected hilar lymph node (LN) metastases should undergo invasive mediastinal LN staging prior to surgical treatment via endosonography. We evaluated the diagnostic performance of endosonography for detecting occult mediastinal metastases (OMM) and determined the factors associated with OMM in NSCLC patients with radiological N1. Patients with confirmed primary NSCLC with radiological N1 who underwent endosonography for nodal staging assessment from January 2013 to December 2019 were retrospectively analyzed. The prevalence of OMM was found to be 83/279 (29.7%) and only 38.6% (32/83) were diagnosed via endosonography. However, five of them were confirmed as N3 by endosonography. The overall diagnostic sensitivity, negative predictive value, accuracy, and area under the curve of endosonography were 38.6%, 79.4%, 81.7%, and 0.69, respectively. In multivariable analysis, central tumor (adjusted odds ratio [aOR], 2.05; 95% confidence interval [CI], 1.15-3.68; p=0.016), solid tumor (aOR, 10.24; 95% CI, 1.32-79.49; p=0.026), and adenocarcinoma (aOR, 3.01; 95% CI, 1.63-5.55; p<0.001) were related to OMM in radiological N1 NSCLC patients. Although the sensitivity of endosonography for detecting OMM was only 40%, the prevalence of OMM was not low (30%) and some cases even turned out to be N3 diseases. Clinicians should be aware that OMM may be more likely in patients with central, solid, and adenocarcinomatous tumor when performing nodal staging in radiological N1 NSCLC via endosonography.

Metastasectomy for colorectal pulmonary metastases: a survey among members of the European Society of Thoracic Surgeons.

Surgical management of pulmonary metastases in colorectal cancer patients is a debated topic. There is currently no consensus on this matter, which sparks considerable risk for international practice variation. The European Society of Thoracic Surgeons (ESTS) ran a survey to assess current clinical practices and to determine criteria for resection among ESTS members. All ESTS members were invited to complete an online questionnaire of 38 questions on current practice and management of pulmonary metastases in colorectal cancer patients. In total, 308 complete responses were received (response rate: 22%) from 62 countries. Most respondents consider that pulmonary metastasectomy for colorectal pulmonary metastases improves disease control (97%) and improves patients' survival (92%). Invasive mediastinal staging in case of suspicious hilar or mediastinal lymph nodes is indicated (82%). Wedge resection is the preferred type of resection for a peripheral metastasis (87%). Minimally invasive approach is the preferred approach (72%). For a centrally located colorectal pulmonary metastasis, the preferred form of treatment is a minimally invasive anatomical resection (56%). During metastasectomy, 67% of respondents perform mediastinal lymph node sampling or dissection. Routine chemotherapy is rarely or never given following metastasectomy (57% of respondents). This survey among the ESTS members underlines the change in practice of pulmonary metastasectomy with an increasing tendency in favour of minimally invasive metastasectomy and surgical resection is preferred over other types of local treatment. Criteria for resectability vary and controversy remains regarding lymph node assessment and the role of adjuvant treatment.

EBUS-TBNA versus mediastinoscopy for mediastinal staging of lung cancer: a cost-minimization analysis

ABSTRACTObjective:To assess cost differences between EBUS-TBNA and mediastinoscopy for mediastinal staging of non-small cell lung cancer (NSCLC). Methods:This was an economic evaluation study with a cost-minimization analysis. We used a decision analysis software program to construct a decision tree model to compare the downstream costs of mediastinoscopy, EBUS-TBNA without surgical confirmation of negative results, and EBUS-TBNA with surgical confirmation of negative results for the mediastinal staging of NSCLC. The study was conducted from the perspective of the Brazilian public health care system. Only direct medical costs were considered. Results are shown in Brazilian currency (Real; R$) and in International Dollars (I$). Results:For the base-case analysis, initial evaluation with EBUS-TBNA without surgical confirmation of negative results was found to be the least costly strategy (R$1,254/I$2,961) in comparison with mediastinoscopy (R$3,255/I$7,688) and EBUS-TBNA with surgical confirmation of negative results (R$3,688/I$8,711). The sensitivity analyses also showed that EBUS-TBNA without surgical confirmation of negative results was the least costly strategy. Mediastinoscopy would become the least costly strategy if the costs for hospital supplies for EBUS-TBNA increased by more than 300%. EBUS-TBNA with surgical confirmation of negative results, in comparison with mediastinoscopy, will be less costly if the prevalence of mediastinal lymph node metastasis is ≥ 38%. Conclusions:This study has demonstrated that EBUS-TBNA is the least costly strategy for invasive mediastinal staging of NSCLC in the Brazilian public health care system.

Mediastinal Staging with Endobronchial Ultrasound in Early-Stage Non—Small Cell Lung Cancer: Is It Necessary?

Herein we examine the need for minimally invasive mediastinal staging for patients with early-stage non-small cell lung cancer (NSCLC) using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). Early NSCLC, stages 1 and 2, has a 5-year survival rate between 53 and 92%, whereas stages 3 and 4 have a 5-year survival of 36% and below. With more favorable outcomes in earlier stages, greater emphasis has been placed on identifying lung cancer earlier in its disease process. Accurate staging is crucial as it dictates both prognosis and therapy. Inaccurate staging can adversely impact surgical candidacy (if falsely "over-staged") or lead to inadequate treatment (if "under-staged"). Clinical staging utilizes noninvasive methods to evaluate the anatomic extent of disease; however, it remains controversial whether mediastinal staging of early NSCLC with radiological exams alone is sufficient. EBUS-TBNA has altered the landscape of invasive mediastinal staging and is a crucial component to improving confidence in lung cancer staging, specifically in early NSCLC. Radiographic occult lymph node metastasis identified upon review of surgical resection specimens of early NSCLC may support the argument to perform EBUS-TBNA in all cases of early-stage disease. Other data suggest that EBUS-TBNA could be spared in cases of peripheral cT1aN0 and cT1bN0 for which surgical resection with lymph node dissection is planned. By reviewing reported EBUS-TBNA outcomes in patients with early NSCLC, we aim to emphasize the necessity of staging with EBUS in this population.

Commentary: Targeted sampling during endobronchial ultrasound: Additional prerequisites for clinical implementation

Evaluating the mediastinal lymph nodes is crucial for staging and leads to accurate lung cancer treatment plans and prognosis predictions. Because computed tomography and positron emission tomography have high false-positive rates and relatively low sensitivity and specificity, invasive mediastinal staging plays a vital role in the histologic confirmation of metastasis and ruling out false positives. Currently available lung cancer guidelines from the National Comprehensive Cancer Network, the European Society of Thoracic Surgeons, and the American College of Chest Physicians emphasize the use of invasive mediastinal staging in some groups of patients who have a high probability of node metastasis.

Interventional Pulmonology and Esophagus: Combined Endobronchial Ultrasound and Endoscopic Ultrasound for Mediastinal Staging.

Endoscopic ultrasound (EUS) techniques in addition to endobronchial ultrasound (EBUS) can lead to diagnosis and complete accurate staging of the mediastinum in a single session. This allows for decreased health care costs, less delay in diagnosis and treatment, reduced patient discomfort, and decreased morbidity compared with invasive surgical staging techniques. In comparison to conventional mediastinoscopy, the cost-effectiveness and reduced complication profile of the endoscopic approach has made this a superior initial step in the staging and diagnosis of lung cancer. Moreover, compared with EBUS alone, combined EUS and EBUS has significantly increased yield, as well as diagnostic sensitivity making a combined approach preferable as the emerging gold-standard technique for initial minimally invasive mediastinal staging. We discuss the advantage of using EUS in combination with EBUS and highlight techniques, lymph node landmarks, utility in staging and restaging of the mediastinum, roles in diagnosing mediastinal infections and granulomatous lesions, and future directions in endosonography.

Endoscopic nodal staging in oligometastatic non-small cell lung cancer (NSCLC) being treated with stereotactic ablative radiotherapy (ENDO-SABR)

BackgroundResearch in treatment of non-small cell lung cancer (NSCLC) has shown promising results with stereotactic ablative radiotherapy (SABR) of oligometastatic disease, wherein distant disease may be limited to one or a few distant organs by host factors. Traditionally, PET/CT has been used in detecting metastatic disease and avoiding futile surgical intervention, however, sensitivity and specificity is limited to only 81 and 79%, respectively. Mediastinal staging still identifies occult nodal disease in up to 20% of NSCLC patients initially thought to be operative candidates. Endobronchial ultrasound and transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive tool for the staging and diagnosis of thoracic malignancy. When EBUS is combined with endoscopic ultrasound using the same bronchoscope (EUS-B), the diagnostic sensitivity and negative predictive value increase to 84 and 97%, respectively. Endoscopic staging in patients with advanced disease has never been studied, but may inform treatment if a curative SABR approach is being taken.MethodsThis is a multi-centre, prospective, cohort study with two-stage design. In the first stage, 10 patients with oligometastatic NSCLC (lung tumour ± hilar/mediastinal lymphadenopathy) with up to 5 synchronous metastases will be enrolled An additional 19 patients will be enrolled in the second stage if rate of treatment change is greater than 10% in the first stage. Patients will be subject to EBUS or combined modality EBUS/EUS-B to assess bilateral lymph node stations using a N3 to N2 to N1 progression. Primary endpoint is defined as the rate of change to treatment plan including change from SABR to conventional dose radiation, change in mediastinal radiation field, and change from curative to palliative intent treatment.DiscussionIf a curative approach with SABR for oligometastatic disease is being explored, invasive mediastinal staging may guide treatment and prognosis. This study will provide insight into the use of endoscopic mediastinal staging in determining changes in treatment plan of NSCLC. Results will inform the design of future phase II trials.Trial registrationClinicaltrials.gov identifier NCT04852588. Date of registration: April 19, 2021. Protocol version: 1.1 on December 9, 2021.

Survival of Non-Small Cell Lung Cancer Patients with Unexpected N2 after Complete Resection: Role of Aggressive Invasive Mediastinal Staging should be Considered

Objective: Mediastinal lymph node (N2) metastasis is one of the poor prognostic factors in non-small cell lung cancer patients (NSCLC). However, the accuracy of mediastinal lymph node staging in real practice is uncertain and inadequate. Consequently, the aim of this study was to determine the survival of NSCLC patients with clinically non-suspicious mediastinal lymph node metastases who underwent complete resection but were pathologically confirmed as having N2 metastases (unexpected N2).Materials and Methods: A retrospective review was performed of all pathology-proven N2 metastases NSCLC patients who underwent curative surgical resection from January 2007 to December 2016. A total of 158 patients were initially included in the study. After the exclusions (known N2, small cell carcinomas, neuroendocrine tumor), 125 unexpected N2 patients who underwent complete resection were analyzed. Survival analysis was determined using the Kaplan–Meier method and multivariate analysis was determined using the Cox regression method.Results: The overall 2-year, 3-year, and 5-year survival rates were 40%, 24%, and 20% respectively. Complete resection was achieved in all patients. Invasive mediastinal staging (IMS) was performed in 47 patients (37.6%), by endobronchial ultrasonography (EBUS) in 46 (36.8%) patients (82.6% negative and 17.4% inadequate tissue) while only 1 patient underwent mediastinoscopy. The factors affecting the survival rate upon comparison were the histology type (p=0.019), differentiate characteristics (p=0.004), adjuvant therapy (p=0.011), and presence of distant metastasis by postoperative re-staging (p=0.003). The independent predictive factors for survival werechemo-radiation therapy (odds ratio 0.367, 95% confidence interval 0.176–0.766) and distant metastasis (odds ratio 2.280, 95% confidence interval 1.334–3.897). However, a small size, periphery lesion, T staging, and number of N2 lesions were not significant factors.Conclusion: The survival rate of unexpected N2 patients was low despite complete resection being achieved in these patients. Adjuvant therapy seemed to improve survival for those with unexpected N2 metastasis as it is a systemic disease. However, not all patients received IMS, which was mostly done by EBUS and which had a high false negative, leading to underestimating the staging. Other modalities, such as cervical mediastinoscopy, videoassisted mediastinoscopic lymphadenectomy (VAMLA) or open biopsy should be considered for the adequate evaluation of N2 metastasis, nonetheless further study is still needed.

The Relative Survival Impact of Guideline-Concordant Clinical Staging and Stage-Appropriate Treatment of Potentially Curable Non-Small Cell Lung Cancer

Lung cancer management guidelines strive to improve outcomes. Theoretically, thorough staging promotes optimal treatment selection. We examined the association between guideline-concordant invasive mediastinal nodal staging, guideline-concordant treatment, and non-small cell lung cancer survival. What is the current practice of invasive mediastinal nodal staging for patients with lung cancer in a structured multidisciplinary care environment? Is guideline-concordant staging associated with guideline-concordant treatment? How do they relate to survival? We evaluated patients with nonmetastatic non-small cell lung cancer diagnosed from 2014 through 2019 in the Multidisciplinary Thoracic Oncology Program of the Baptist Cancer Center, Memphis, Tennessee. We examined patterns of mediastinal nodal staging and stage-stratified treatment, grouping patients into cohorts with guideline-concordant staging alone, guideline-concordant treatment alone, both, or neither. We evaluated overall survival with Kaplan-Meier curves and Cox proportional hazards models. Of 882 patients, 456 (52%) received any invasive mediastinal staging. Seventy-four percent received guideline-concordant staging; guideline-discordant staging decreased from 34%in 2014 to 18%in 2019 (P< .0001). Recipients of guideline-concordant staging were more likely to receive guideline-concordant treatment (83%vs66%; P< .0001). Sixty-one percent received both guideline-concordant invasive mediastinal staging and guideline-concordant treatment; 13%received guideline-concordant staging alone; 17%received guideline-concordant treatment alone; and 9%received neither. Survival was greatest in patients who received both (adjusted hazard ratio [aHR], 0.41; 95%CI, 0.26-0.63), followed by those who received guideline-concordant treatment alone (aHR, 0.60; 95%CI, 0.36-0.99), and those who received guideline-concordant staging alone (aHR, 0.64; 95%CI, 0.37-1.09) compared with neither (P< .0001, log-rank test). Levels of guideline-concordant staging were high, were rising, and were associated with guideline-concordant treatment selection in this multidisciplinary care cohort. Guideline-concordant staging and guideline-concordant treatment were complementary in their association with improved survival, supporting the connection between these two processes and lung cancer outcomes.

Clinical Validation of the Canada Lymph Node Score for Endobronchial Ultrasound

BackgroundThe Canada Lymph Node Score (CLNS) uses 4 sonographic criteria to predict the risk of malignancy in lymph nodes during endobronchial ultrasound. The CLNS may play a role in identifying targets for biopsy or rebiopsy during invasive mediastinal staging for lung cancer. However the CLNS has not yet been prospectively validated in routine clinical practice. MethodsCLNSs for each lymph node biopsied during endobronchial ultrasound were prospectively captured for 1 year (2019). The CLNS and the presence of malignancy in each node were compared. Univariate binary logistic regression was completed for each ultrasonographic feature and multivariate logistic regression model. ResultsCLNSs and diagnostic pathology results were available for 367 lymph nodes. Incidence of malignancy increased with higher scores. Scores ≥ 3 were significantly associated with malignancy (specificity, 84.4%; positive likelihood ratio, 4.0). Area under the curve was 0.76, indicating a good ability of the model to predict presence or absence of malignancy. Nodes scoring < 2 and negative on computed tomography and positron emission tomography were malignant in 10.1%. ConclusionsThe CLNS correlates with the presence or absence of malignancy in thoracic lymph nodes and may serve as an adjunct to currently available methods of invasive and noninvasive mediastinal staging. The CLNS may be most helpful in selecting which nondiagnostic lymph nodes require rebiopsy. There is a significant risk of a false-negative result even with a score of 0, and using a combination of low CLNSs and negative conventional radiology to obviate the need for any initial biopsy remains to be studied in prospective trials.

Invasive mediastinal staging of non-small-cell lung cancer: immediate results and a role in determining treatment policy

Invasive mediastinal staging of non-small-cell lung cancer: immediate results and a role in determining treatment policy