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

Abstract

BackgroundPrediction 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).Research QuestionCan mediastinal metastasis and its detection by EBUS-TBNA be predicted with prediction models in NSCLC?Study Design and MethodsFor 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).ResultsThe 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 (> 3-5 cm), 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.InterpretationPLUS-M and PLUS-E can be used effectively for decision-making for invasive mediastinal staging in NSCLC.Trial RegistryClinicalTrials.gov; No.: NCT02991924; URL: www.clinicaltrials.gov 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 (> 3-5 cm), 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.clinicaltrials.gov Take-home PointsStudy Question: Can mediastinal metastasis and its detection by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) be predicted with prediction models in non-small cell lung cancer (NSCLC)?Results: The prediction model for lung cancer staging-mediastinal metastasis (PLUS-M) and the prediction model for lung cancer staging-mediastinal metastasis detection by EBUS-TBNA (PLUS-E) were developed using age, histologic type, tumor location, tumor size, clinical N stage by CT and clinical N stage by PET-CT. PLUS-M and PLUS-E showed good discrimination ability and calibration.Interpretation: PLUS-M and PLUS-E can be used effectively for decision-making for invasive mediastinal staging in NSCLC. Study Question: Can mediastinal metastasis and its detection by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) be predicted with prediction models in non-small cell lung cancer (NSCLC)? Results: The prediction model for lung cancer staging-mediastinal metastasis (PLUS-M) and the prediction model for lung cancer staging-mediastinal metastasis detection by EBUS-TBNA (PLUS-E) were developed using age, histologic type, tumor location, tumor size, clinical N stage by CT and clinical N stage by PET-CT. PLUS-M and PLUS-E showed good discrimination ability and calibration. Interpretation: PLUS-M and PLUS-E can be used effectively for decision-making for invasive mediastinal staging in NSCLC. Invasive mediastinal staging is an important step that guides treatment decision-making in non-small cell lung cancer (NSCLC).1Silvestri G.A. Gonzalez A.V. Jantz M.A. et al.Methods for staging non-small cell lung cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.Chest. 2013; 143: e211S-e250SAbstract Full Text Full Text PDF PubMed Scopus (1120) Google Scholar, 2De 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 PubMed Scopus Google Scholar, J. and non-small-cell lung cancer: an of the clinical practice guidelines and Full Text Full Text PDF PubMed Scopus Google endobronchial ultrasound-guided transbronchial needle aspiration with of et prospective of endobronchial ultrasound-guided transbronchial needle aspiration compared with for mediastinal lymph node staging of lung Full Text Full Text PDF PubMed Scopus Google et for mediastinal staging of non-small-cell lung Full Text Full Text PDF PubMed Scopus Google is a for invasive G.A. Gonzalez A.V. Jantz M.A. et al.Methods for staging non-small cell lung cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.Chest. 2013; 143: e211S-e250SAbstract Full Text Full Text PDF PubMed Scopus (1120) Google 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 PubMed Scopus Google guidelines for mediastinal staging in NSCLC invasive staging for risk for mediastinal G.A. Gonzalez A.V. Jantz M.A. et al.Methods for staging non-small cell lung cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.Chest. 2013; 143: e211S-e250SAbstract Full Text Full Text PDF PubMed Scopus (1120) Google 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 PubMed Scopus Google P. et endobronchial and for the and staging of lung cancer: of in with the and the of Scholar, Mediastinal staging for lung Full Text Full Text PDF PubMed Scopus Google Scholar, for and cancer: and for and Scholar, cell lung in of preoperative staging is in patients with clinical N (cN) disease by CT or a central tumor or a tumor in 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 PubMed Scopus Google guidelines invasive staging for disease by CT, cN2-3 disease by and central with and not invasive staging for of with disease by CT and G.A. Gonzalez A.V. Jantz M.A. et al.Methods for staging non-small cell lung cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.Chest. 2013; 143: e211S-e250SAbstract Full Text Full Text PDF PubMed Scopus (1120) Google for and guidelines have a for invasive mediastinal disease by CT or for and cancer: and for and risk factors for mediastinal lymph node metastasis in clinical stage non-small-cell lung cancer Full Text Full Text PDF PubMed Scopus Google Scholar, clinical prediction the of mediastinal metastasis in patients with non-small cell lung Full Text Full Text PDF PubMed Google Scholar, J. 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Gonzalez A.V. Jantz M.A. et al.Methods for staging non-small cell lung cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.Chest. 2013; 143: e211S-e250SAbstract Full Text Full Text PDF PubMed Scopus (1120) Google 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 PubMed Scopus Google for and cancer: and for and and validation the ESTS were in the development cohort, the sensitivity for N2-3 EBUS-TBNA N2-3 disease detection and N2-3 disease were and respectively. a PLUS-M was were and respectively. 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Jantz M.A. et al.Methods for staging non-small cell lung cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.Chest. 2013; 143: e211S-e250SAbstract Full Text Full Text PDF PubMed Scopus (1120) Google (n = disease by CT or PET-CT or central from the for and cancer: and for and (n = disease by CT or ≥ (n = ≥ (n = ≥ (n = ≥ (n = ≥ (n = ≥ (n = ≥ and PLUS-E ≥ (n = (95% EBUS-TBNA = endobronchial ultrasound-guided transbronchial needle ESTS = of = for and PLUS-E = prediction model for lung cancer staging-mediastinal metastasis detection by endobronchial ultrasound-guided transbronchial needle PLUS-M = prediction model for lung cancer staging-mediastinal The PLUS-M and PLUS-E of central tumor was used for the The of N2-3 disease diagnosed by lymph node surgery is performed in patients with disease by EBUS-TBNA or for EBUS-TBNA guidelines and disease by CT or central or tumor disease by CT or PET-CT or central from the disease by CT or PET-CT. in a (95% EBUS-TBNA = endobronchial ultrasound-guided transbronchial needle ESTS = of = for and PLUS-E = prediction model for lung cancer staging-mediastinal metastasis detection by endobronchial ultrasound-guided transbronchial needle PLUS-M = prediction model for lung cancer staging-mediastinal developed prediction models for mediastinal metastasis (PLUS-M) and its detection by EBUS-TBNA (PLUS-E) in potentially operable NSCLC. prediction models the EBUS-TBNA and staging from a prospective cohort mediastinal metastasis and its detection by EBUS-TBNA was performed in and stage was in patients without mediastinal metastasis by CT and PET-CT were performed the of N cN1 staging by CT age (< 60 years and 60-70 years), nonsquamous central location, tumor size (> 3-5 cm), cN1 or cN2-3 stage by CT, and cN1 or cN2-3 stage by PET-CT were risk factors for N2-3 disease diagnosed by EBUS-TBNA or were with PLUS-M and PLUS-E in the development were using for PLUS-M and PLUS-E were in the validation showed of fit for PLUS-M and PLUS-E in the development and validation prediction models for mediastinal metastasis have been The model was developed using a cohort (n = and with a prospective et prediction model with the of in lung cancer: J PubMed Scopus Google et lymph node metastasis in non-small cell lung cancer: prospective and validation of the and Full Text Full Text PDF PubMed Scopus Google The model was developed using EBUS-TBNA without surgery age, central location, and N stage by PET-CT were with a of cN2-3 disease by EBUS-TBNA (AUC, et prediction model with the of in lung cancer: J PubMed Scopus Google et et model for disease patients with non-small cell lung Full Text Full Text PDF PubMed Scopus Google developed a prediction model metastasis using a prospective cohort (n = = Model were tumor size and location, by CT or and tumor (AUC, The was and not model by and clinical prediction the of mediastinal metastasis in patients with non-small cell lung Full Text Full Text PDF PubMed Google used and surgery for staging (n = by CT and were not in the model (AUC, et J. et prediction model invasive mediastinal staging for non-small cell lung cancer in patients with a the Prediction Full Text Full Text PDF PubMed Scopus Google developed the prediction model mediastinal metastasis in NSCLC with = using tumor location, the mediastinal size, of cN1 and tumor (AUC, prediction models have evaluated the of mediastinal metastasis in retrospective risk factors for mediastinal lymph node metastasis in clinical stage non-small-cell lung cancer Full Text Full Text PDF PubMed Scopus Google J. J. and validation of a clinical prediction model for lymph node metastasis in non-small cell lung 2013; Full Text Full Text PDF PubMed Scopus Google J. prediction model for disease in non-small cell lung Full Text Full Text PDF PubMed Scopus Google et lymph in patients with cell lung Scopus Google C. prediction model for disease in lung cancer patients with a by 2013; Full Text Full Text PDF PubMed Scopus Google prediction models using or have been J. of mediastinal lymph in NSCLC in different of CT PubMed Scopus Google Scholar, J. C. risk a for risk of lymph node metastasis in patients with non-small cell lung J PubMed Google Scholar, J. C. et prediction of lymph node metastasis in patients with non-small cell lung cancer by PubMed Scopus Google guidelines invasive staging for risk of patients with G.A. Gonzalez A.V. Jantz M.A. et al.Methods for staging non-small cell lung cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.Chest. 2013; 143: e211S-e250SAbstract Full Text Full Text PDF PubMed Scopus (1120) Google 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 PubMed Scopus Google P. et endobronchial and for the and staging of lung cancer: of in with the and the of for and cancer: and for and cell lung in In PLUS-M, cN1 or cN2-3 stage by CT and cN1 or cN2-3 stage by PET-CT were significant risk factors for mediastinal with G.A. Gonzalez A.V. Jantz M.A. et al.Methods for staging non-small cell lung cancer: Diagnosis and Management of Lung Cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines.Chest. 2013; 143: e211S-e250SAbstract Full Text Full Text PDF PubMed Scopus (1120) Google 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 PubMed Scopus Google P. et endobronchial and for the and staging of lung cancer: of in with the and the of for and cancer: and for and stage by PET-CT showed a stage by The risk from central tumor was not compared with risk tumor using from the et of a central is of mediastinal metastasis in cell lung cancer patients with J. PubMed Scopus Google using of tumor be et prediction model with the of in lung cancer: J PubMed Scopus Google et of a central is of mediastinal metastasis in cell lung cancer patients with J. PubMed Scopus Google size of and was a significant risk for N2-3 disease the risk by size of was not significant in multivariable be its with risk of and the younger age (< 60 60-70 was a risk for mediastinal prediction models younger age a risk of N2-3 risk factors for mediastinal lymph node metastasis in clinical stage non-small-cell lung cancer Full Text Full Text PDF PubMed Scopus Google Scholar, clinical prediction the of mediastinal metastasis in patients with non-small cell lung Full Text Full Text PDF PubMed Google Scholar, J. J. and validation of a clinical prediction model for lymph node metastasis in non-small cell lung 2013; Full Text Full Text PDF PubMed Scopus Google Scholar, et prediction model with the of in lung cancer: J PubMed Scopus Google Scholar, J. prediction model for disease in non-small cell lung Full Text Full Text PDF PubMed Scopus Google be tumor and the detection of cancer a younger et cell lung in age is with stage and a in patients that not have a a PubMed Scopus Google used 60 years and 70 years the for age clinical have used or age a for the of age a of N2-3 risk factors for mediastinal lymph node metastasis in clinical stage non-small-cell lung cancer Full Text Full Text PDF PubMed Scopus Google Scholar, clinical prediction the of mediastinal metastasis in patients with non-small cell lung Full Text Full Text PDF PubMed Google Scholar, J. J. and validation of a clinical prediction model for lymph node metastasis in non-small cell lung 2013; Full Text Full Text PDF PubMed Scopus Google Scholar, et prediction model with the of in lung cancer: J PubMed Scopus Google Scholar, J. prediction model for disease in non-small cell lung Full Text Full Text PDF PubMed Scopus Google Scholar, et lymph in patients with cell lung Scopus Google In PLUS-M, and nonsquamous histology were risk factors compared with cell in multivariable with histologic cell was in J. J. and validation of a clinical prediction model for lymph node metastasis in non-small cell lung 2013; Full Text Full Text PDF PubMed Scopus Google a risk for N2-3 disease

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