Selection of modality for diagnosis and staging of patients with suspected non-small cell lung cancer
- Karl W Thomas, MD
Karl W Thomas, MD
- Professor of Medicine - Pulmonary, Critical Care, Allergy and Immunology
- Wake Forest School of Medicine
- Michael K Gould, MD, MS
Michael K Gould, MD, MS
- Senior Research Scientist
- Director for Health Services Research
- Department of Research and Evaluation
- Kaiser Permanente Southern California
- Section Editor
- David E Midthun, MD
David E Midthun, MD
- Section Editor — Lung Cancer
- Professor of Medicine, Mayo Clinic College of Medicine
- Deputy Editors
- Geraldine Finlay, MD
Geraldine Finlay, MD
- Senior Deputy Editor — UpToDate
- Deputy Editor — Pulmonary, Critical Care, and Sleep Medicine
- Associate Professor
- Tufts University School of Medicine
- Susanna I Lee, MD, PhD
Susanna I Lee, MD, PhD
- Deputy Editor — Radiology
- Associate Professor of Radiology
- Harvard Medical School
- Massachusetts General Hospital
Non-small cell lung cancer (NSCLC) accounts for approximately 85 percent of all lung cancers . The two most common histopathologic subtypes are adenocarcinoma and squamous carcinoma. Tissue biopsy is necessary for the diagnosis and staging of NSCLC so that appropriate therapies can be administered in a timely fashion. (See "Personalized, genotype-directed therapy for advanced non-small cell lung cancer".)
This topic will discuss the general approach to selecting a modality to obtain tissue from a target biopsy site (primary tumor, lymph node, distant metastasis) in patients with suspected NSCLC. The approach to patients with a solitary pulmonary nodule, overview of the initial evaluation and imaging of NSCLC, procedures used for tissue biopsy of NSCLC, and the Tumor Node Metastasis staging system for NSCLC are discussed in detail separately. (See "Diagnostic evaluation and management of the solitary pulmonary nodule" and "Overview of the risk factors, pathology, and clinical manifestations of lung cancer" and "Overview of the initial evaluation, treatment and prognosis of lung cancer" and "Overview of the initial evaluation, diagnosis, and staging of patients with suspected lung cancer" and "Procedures for tissue biopsy in patients with suspected non-small cell lung cancer" and "Tumor, Node, Metastasis (TNM) staging system for lung cancer".)
The acquisition of tissue from the primary lung lesion or suspected metastases (eg, lymph nodes or distant organs) should ideally provide enough material for a timely and accurate histopathologic diagnosis with molecular characterization. Computed tomographic (CT), positron emission tomographic (PET) scanning, and/or other imaging modalities (eg, magnetic resonance imaging [MRI]) guide the clinician in choosing the optimal site(s) for tissue sampling. The goals must be balanced with minimizing patient risk and accommodating patient preferences. The goals do not necessarily change for patients with significant comorbid disease or those with suspected advanced-stage disease. However, the risks and potential complications of biopsy in these patients may limit the preferred options. (See 'Assessing patient risk' below.)
Efficient diagnosis and procedures — The preferred initial site for tissue biopsy is one that could simultaneously establish the histopathologic diagnosis and disease stage. However, if the initial selected diagnostic procedure does not establish the diagnosis or stage, additional procedures are necessary. Exceptions to this general approach may occur in patients with multiple limiting comorbidities or those with unambiguous clinical and radiographic evidence of metastasis.
- Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015; 65:5.
- Goldstraw P, Chansky K, Crowley J, et al. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. J Thorac Oncol 2016; 11:39.
- AJCC (American Joint Committee on Cancer) Cancer Staging Manual, 8th edition, Amin MB, Edge SB, Greene FL et al. (Eds), Springer, Chicago 2017.
- Travis WD, Brambilla E, Van Schil P, et al. Paradigm shifts in lung cancer as defined in the new IASLC/ATS/ERS lung adenocarcinoma classification. Eur Respir J 2011; 38:239.
- Ellis PM, Blais N, Soulieres D, et al. A systematic review and Canadian consensus recommendations on the use of biomarkers in the treatment of non-small cell lung cancer. J Thorac Oncol 2011; 6:1379.
- Travis WD, Brambilla E, Noguchi M, et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 2011; 6:244.
- Travis WD, Brambilla E, Riely GJ. New pathologic classification of lung cancer: relevance for clinical practice and clinical trials. J Clin Oncol 2013; 31:992.
- Dietel M, Bubendorf L, Dingemans AM, et al. Diagnostic procedures for non-small-cell lung cancer (NSCLC): recommendations of the European Expert Group. Thorax 2016; 71:177.
- Lim EH, Zhang SL, Li JL, et al. Using whole genome amplification (WGA) of low-volume biopsies to assess the prognostic role of EGFR, KRAS, p53, and CMET mutations in advanced-stage non-small cell lung cancer (NSCLC). J Thorac Oncol 2009; 4:12.
- Quinn AM, Hickson N, Adaway M, et al. Diagnostic Mutation Profiling and Validation of Non-Small-Cell Lung Cancer Small Biopsy Samples using a High Throughput Platform. J Thorac Oncol 2015; 10:784.
- Nakajima T, Yasufuku K, Takahashi R, et al. Comparison of 21-gauge and 22-gauge aspiration needle during endobronchial ultrasound-guided transbronchial needle aspiration. Respirology 2011; 16:90.
- Loukeris K, Vazquez MF, Sica G, et al. Cytological cell blocks: Predictors of squamous cell carcinoma and adenocarcinoma subtypes. Diagn Cytopathol 2012; 40:380.
- Ost DE, Ernst A, Lei X, et al. Diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration: results of the AQuIRE Bronchoscopy Registry. Chest 2011; 140:1557.
- Oki M, Saka H, Kitagawa C, et al. Randomized Study of 21-gauge Versus 22-gauge Endobronchial Ultrasound-guided Transbronchial Needle Aspiration Needles for Sampling Histology Specimens. J Bronchology Interv Pulmonol 2011; 18:306.
- Yarmus LB, Akulian J, Lechtzin N, et al. Comparison of 21-gauge and 22-gauge aspiration needle in endobronchial ultrasound-guided transbronchial needle aspiration: results of the American College of Chest Physicians Quality Improvement Registry, Education, and Evaluation Registry. Chest 2013; 143:1036.
- Bulman W, Saqi A, Powell CA. Acquisition and processing of endobronchial ultrasound-guided transbronchial needle aspiration specimens in the era of targeted lung cancer chemotherapy. Am J Respir Crit Care Med 2012; 185:606.
- Mondoni M, Carlucci P, Di Marco F, et al. Rapid on-site evaluation improves needle aspiration sensitivity in the diagnosis of central lung cancers: a randomized trial. Respiration 2013; 86:52.
- Navani N, Brown JM, Nankivell M, et al. Suitability of endobronchial ultrasound-guided transbronchial needle aspiration specimens for subtyping and genotyping of non-small cell lung cancer: a multicenter study of 774 patients. Am J Respir Crit Care Med 2012; 185:1316.
- Bonifazi M, Sediari M, Ferretti M, et al. The role of the pulmonologist in rapid on-site cytologic evaluation of transbronchial needle aspiration: a prospective study. Chest 2014; 145:60.
- Yarmus L, Akulian J, Gilbert C, et al. Optimizing endobronchial ultrasound for molecular analysis. How many passes are needed? Ann Am Thorac Soc 2013; 10:636.
- de Kock I, Mirhosseini M, Lau F, et al. Conversion of Karnofsky Performance Status (KPS) and Eastern Cooperative Oncology Group Performance Status (ECOG) to Palliative Performance Scale (PPS), and the interchangeability of PPS and KPS in prognostic tools. J Palliat Care 2013; 29:163.
- Subramaniam S, Thorns A, Ridout M, et al. Accuracy of prognosis prediction by PPI in hospice inpatients with cancer: a multi-centre prospective study. BMJ Support Palliat Care 2015; 5:399.
- Morita T, Tsunoda J, Inoue S, Chihara S. The Palliative Prognostic Index: a scoring system for survival prediction of terminally ill cancer patients. Support Care Cancer 1999; 7:128.
- Wiener RS, Schwartz LM, Woloshin S, Welch HG. Population-based risk for complications after transthoracic needle lung biopsy of a pulmonary nodule: an analysis of discharge records. Ann Intern Med 2011; 155:137.
- Silvestri GA, Gonzalez AV, Jantz MA, 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.
- Rivera MP, Mehta AC, Wahidi MM. Establishing the diagnosis of lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143:e142S.
- De Leyn P, Lardinois D, Van Schil P, et al. European trends in preoperative and intraoperative nodal staging: ESTS guidelines. J Thorac Oncol 2007; 2:357.
- Ost DE, Yeung SC, Tanoue LT, Gould MK. Clinical and organizational factors in the initial evaluation of patients with lung cancer: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143:e121S.
- Vilmann P, Clementsen PF, Colella S, et al. Combined endobronchial and esophageal endosonography for the diagnosis and staging of lung cancer: European Society of Gastrointestinal Endoscopy (ESGE) Guideline, in cooperation with the European Respiratory Society (ERS) and the European Society of Thoracic Surgeons (ESTS). Endoscopy 2015; 47:545.
- Gaga M, Powell CA, Schraufnagel DE, et al. An official American Thoracic Society/European Respiratory Society statement: the role of the pulmonologist in the diagnosis and management of lung cancer. Am J Respir Crit Care Med 2013; 188:503.
- De Wever W. Role of integrated PET/CT in the staging of non-small cell lung cancer. JBR-BTR 2009; 92:124.
- Fischer B, Lassen U, Mortensen J, et al. Preoperative staging of lung cancer with combined PET-CT. N Engl J Med 2009; 361:32.
- Maziak DE, Darling GE, Inculet RI, et al. Positron emission tomography in staging early lung cancer: a randomized trial. Ann Intern Med 2009; 151:221.
- Gómez-Caro A, Garcia S, Reguart N, et al. Incidence of occult mediastinal node involvement in cN0 non-small-cell lung cancer patients after negative uptake of positron emission tomography/computer tomography scan. Eur J Cardiothorac Surg 2010; 37:1168.
- Pozo-Rodríguez F, Martín de Nicolás JL, Sánchez-Nistal MA, et al. Accuracy of helical computed tomography and [18F] fluorodeoxyglucose positron emission tomography for identifying lymph node mediastinal metastases in potentially resectable non-small-cell lung cancer. J Clin Oncol 2005; 23:8348.
- Verhagen AF, Bootsma GP, Tjan-Heijnen VC, et al. FDG-PET in staging lung cancer: how does it change the algorithm? Lung Cancer 2004; 44:175.
- Freixinet Gilart J, García PG, de Castro FR, et al. Extended cervical mediastinoscopy in the staging of bronchogenic carcinoma. Ann Thorac Surg 2000; 70:1641.
- Schmidt-Hansen M, Baldwin DR, Hasler E, et al. PET-CT for assessing mediastinal lymph node involvement in patients with suspected resectable non-small cell lung cancer. Cochrane Database Syst Rev 2014; :CD009519.
- Gómez-Caro A, Boada M, Cabañas M, et al. False-negative rate after positron emission tomography/computer tomography scan for mediastinal staging in cI stage non-small-cell lung cancer. Eur J Cardiothorac Surg 2012; 42:93.
- Billé A, Pelosi E, Skanjeti A, et al. Preoperative intrathoracic lymph node staging in patients with non-small-cell lung cancer: accuracy of integrated positron emission tomography and computed tomography. Eur J Cardiothorac Surg 2009; 36:440.
- O'Connell OJ, Almeida FA, Simoff MJ, et al. A Prediction Model to Help with the Assessment of Adenopathy in Lung Cancer (HAL). Am J Respir Crit Care Med 2016.
- Cerfolio RJ, Bryant AS, Ojha B, Eloubeidi M. Improving the inaccuracies of clinical staging of patients with NSCLC: a prospective trial. Ann Thorac Surg 2005; 80:1207.
- Silvestri GA, Vachani A, Whitney D, et al. A Bronchial Genomic Classifier for the Diagnostic Evaluation of Lung Cancer. N Engl J Med 2015; 373:243.
- Ernst A, Anantham D, Eberhardt R, et al. Diagnosis of mediastinal adenopathy-real-time endobronchial ultrasound guided needle aspiration versus mediastinoscopy. J Thorac Oncol 2008; 3:577.
- Herth F, Becker HD, Ernst A. Conventional vs endobronchial ultrasound-guided transbronchial needle aspiration: a randomized trial. Chest 2004; 125:322.
- Yasufuku K, Chiyo M, Koh E, et al. Endobronchial ultrasound guided transbronchial needle aspiration for staging of lung cancer. Lung Cancer 2005; 50:347.
- Herth FJ, Eberhardt R, Vilmann P, et al. Real-time endobronchial ultrasound guided transbronchial needle aspiration for sampling mediastinal lymph nodes. Thorax 2006; 61:795.
- Vincent BD, El-Bayoumi E, Hoffman B, et al. Real-time endobronchial ultrasound-guided transbronchial lymph node aspiration. Ann Thorac Surg 2008; 85:224.
- Gomez M, Silvestri GA. Endobronchial ultrasound for the diagnosis and staging of lung cancer. Proc Am Thorac Soc 2009; 6:180.
- Ong P, Grosu H, Eapen GA, et al. Endobronchial ultrasound-guided transbronchial needle aspiration for systematic nodal staging of lung cancer in patients with N0 disease by computed tomography and integrated positron emission tomography-computed tomography. Ann Am Thorac Soc 2015; 12:415.
- Bonifazi M, Zuccatosta L, Poidomani G, et al. Bullous pemphigoid with the unusual complication of tracheobronchial involvement. Chest 2013; 143:236.
- van der Heijden EH, Casal RF, Trisolini R, et al. Guideline for the acquisition and preparation of conventional and endobronchial ultrasound-guided transbronchial needle aspiration specimens for the diagnosis and molecular testing of patients with known or suspected lung cancer. Respiration 2014; 88:500.
- Annema JT, van Meerbeeck JP, Rintoul RC, et al. Mediastinoscopy vs endosonography for mediastinal nodal staging of lung cancer: a randomized trial. JAMA 2010; 304:2245.
- Wallace MB, Pascual JM, Raimondo M, et al. Minimally invasive endoscopic staging of suspected lung cancer. JAMA 2008; 299:540.
- Light RW, Erozan YS, Ball WC Jr. Cells in pleural fluid. Their value in differential diagnosis. Arch Intern Med 1973; 132:854.
- Prakash UB, Reiman HM. Comparison of needle biopsy with cytologic analysis for the evaluation of pleural effusion: analysis of 414 cases. Mayo Clin Proc 1985; 60:158.
- Mentzer SJ, Swanson SJ, DeCamp MM, et al. Mediastinoscopy, thoracoscopy, and video-assisted thoracic surgery in the diagnosis and staging of lung cancer. Chest 1997; 112:239S.
- Menzies R, Charbonneau M. Thoracoscopy for the diagnosis of pleural disease. Ann Intern Med 1991; 114:271.
- Nguyen P, Feng JC, Chang KJ. Endoscopic ultrasound (EUS) and EUS-guided fine-needle aspiration (FNA) of liver lesions. Gastrointest Endosc 1999; 50:357.
- Uemura S, Yasuda I, Kato T, et al. Preoperative routine evaluation of bilateral adrenal glands by endoscopic ultrasound and fine-needle aspiration in patients with potentially resectable lung cancer. Endoscopy 2013; 45:195.
- Puli SR, Batapati Krishna Reddy J, Bechtold ML, et al. Endoscopic ultrasound: it's accuracy in evaluating mediastinal lymphadenopathy? A meta-analysis and systematic review. World J Gastroenterol 2008; 14:3028.
- Bodtger U, Vilmann P, Clementsen P, et al. Clinical impact of endoscopic ultrasound-fine needle aspiration of left adrenal masses in established or suspected lung cancer. J Thorac Oncol 2009; 4:1485.
- Blackhall F, Thatcher N, Booton R, Kerr K. The impact on the multidisciplinary team of molecular profiling for personalized therapy in non-small cell lung cancer. Lung Cancer 2013; 79:101.
- BIOPSY GOALS
- Efficient diagnosis and procedures
- Adequate biopsy size
- ASSESSING PATIENT RISK
- APPROACH TO THE PATIENT
- General principles
- Assessing radiographic stage
- Low risk N2/N3 mediastinal disease (localized peripheral lung cancer)
- Intermediate and high risk N2/N3 mediastinal disease
- - Intermediate risk N2 and N3 nodal involvement
- - High risk N2 or N3 nodal involvement
- - Modality choice - mediastinal sampling
- EBUS/EUS needle aspiration
- Alternative modalities
- Suspected advanced disease
- - Pleural (T2, T3, M1a)
- - Lung (T3, T4, M1a)
- - Pericardium (T3, M1a)
- - Liver, adrenal gland, brain, bone
- - Supraclavicular or scalene lymph node (N3)
- INDIVIDUALIZING THE APPROACH
- Role of multidisciplinary teams
- TNM STAGING
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS