Chinese Consensus on Early Diagnosis of Primary Lung Cancer (2014 Version)

Transcription

1 Chinese Consensus on Early Diagnosis of Primary Lung Cancer (2014 Version) Jie Hu, MD 1 ; Gui-Sheng Qian, MD 2 ; and Chun-Xue Bai, MD PhD 1,3 ; for the Lung Cancer Study Group of the Chinese Thoracic Society and the Chinese Alliance Against Lung Cancer Expert Group The incidence and mortality of lung cancer in China have rapidly increased. Lung cancer is the leading cause of cancer death in China, possibly because of the inadequate early diagnosis of lung cancer. Reaching a consensus on early diagnostic strategies for lung cancer in China is an unmet needed. Recently, much progress has been made in lung cancer diagnosis, such as screening in high-risk populations, the application of novel imaging technologies, and the use of minimally invasive techniques for diagnosis. However, systemic reviews of disease history, risk assessment, and patients willingness to undergo invasive diagnostic procedures also need to be considered. A diagnostic strategy for lung cancer should be proposed and developed by a multidisciplinary group. A comprehensive evaluation of patient factors and clinical findings should be completed before treatment.cancer 2015;121: VC 2015 American Cancer Society. KEYWORDS: bronchoscopy, diagnosis, lung cancer, screening. INTRODUCTION Primary lung cancer (hereinafter referred to as lung cancer) is a malignant tumor that severely threatens human health. Among all malignant tumors, lung cancer ranks first in both incidence (1,200,000 year) rates according to World Health Organization data published in Between 2000 and 2005, the incidence and mortality of lung cancer in China increased by 116,000 and 101,000 cases, respectively. The impact of the disease is climbing quickly in China, as a result of the rapidly increasing number of smokers. 1 If China does not control smoking and air pollution in a timely manner, then China s annual incidence of lung cancer will be >1,000,000 by the year 2025, and it will become first in the world for lung cancer incidence. 2 The 5-year survival rate of patients with lung cancer is only 17.8%. 1 The main reason for this is that approximately 75% of patients have advanced lung cancer at the time of diagnosis. Because inadequate early diagnosis of lung cancer may lead to a poor prognosis, improving the early diagnosis of lung cancer is an unmet needed. The concept of early diagnosis of lung cancer refers to the correct detection and diagnosis of 3,4 lung cancer in the early stages to increase the proportion of patients diagnosed with early stage disease in the general population, reduce diagnosis time, and treat patients in a timely fashion to achieve the ultimate goal of reducing lung cancer mortality. In this consensus report, we focus on how to detect and diagnose lung cancer in the early stages. Clinical Information Collection Assessment of risk factors Lung cancer is a lifestyle and environmental factor-related disease. The following risk factors are closely associated with the development of lung cancer: Tobacco smoke. Tobacco smoking is a major modifiable risk factor in the development of lung cancer and accounts for 85% of all lung cancer-related deaths. 5 A dose-response relation exists between smoking tobacco and the risk of developing lung cancer. The cessation of tobacco smoking decreases the risk of lung cancer. However, even former smokers have a Corresponding author: Chun-Xue Bai, MD, PhD, Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai , China; Fax: (011) ; bai.chunxue@zs-hospital.sh.cn 1 Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai Respiratory Research Institute, Shanghai, China; 2 Department of Pulmonary Medicine, Xinqiao Hospital of the Third Military Medical University, Chongqing, China; 3 State Key Laboratory of Respiratory Disease, Guangzhou, Guangzhou Medical University, Guangzhou, China See editorial on pages , this issue. All members of the Lung Cancer Study Group of the Chinese Thoracic Society and the Chinese Alliance Against Lung Cancer Expert Group contributed equally to this consensus. DOI: /cncr.29571, Received: May 4, 2015; Revised: June 14, 2015; Accepted: June 16, 2015, Published online September 1, 2015 in Wiley Online Library (wileyonlinelibrary.com) Cancer September 1,

2 higher risk of lung cancer compared with never-smokers. Consequently, a patient s current or past history of tobacco smoking is considered a risk factor for the development of lung cancer, irrespective of the magnitude of exposure and the time since smoking cessation. 6 Environmental pollution. Air pollution caused by industry and automobile exhaust may be related to an increased incidence of lung cancer. Residential air pollution, such as tobacco smoke, indoor living fuel, soot, and cooking oil fumes, also is considered an important risk factor for lung cancer. The latest research demonstrates that 1 lung cancer risk factor that should not to be ignored is radon exposure. Building materials are the most important source of indoor radon in some countries. However, the risk associated with residential radon is uncertain. 7,8 Occupational exposure. Long-term exposure to agents that are identified specifically as carcinogens targeting the lungs include arsenic, chromium, asbestos, nickel, cadmium, beryllium, silica, diesel fumes, coal smoke, and soot. Inhalation or repeated contact with radioactive substances, such as uranium or radium, also contributes to lung cancer. Malignant tumor history. Patients with primary lung cancer, lymphoma, head and neck neoplasms, or smoking-related cancer (such as esophageal carcinoma) have an increased risk of lung cancer. Continued smoking, chest radiotherapy, and alkylating agent treatment also increase the risk of primary lung cancer. Sometimes, these factors add to the risk incurred by smoking. Family history of lung cancer. A history of lung cancer in first-degree relatives carries an increased risk of lung cancer (relative risk, 1.8). 9 Chronic lung disease. A history of chronic obstructive pulmonary disease (COPD) is associated with lung cancer risk, and this association may be largely caused by smoking A family history of chronic bronchitis and emphysema is associated with an increased risk of lung cancer, whereas COPD is associated with lung cancer among never-smokers. Patients with diffuse pulmonary fibrosis seem to be at a higher risk for lung cancer (relative risk, 8.25). Patients with intrapulmonary tuberculosis are also at an increased risk for lung cancer. Generally, once they are symptomatic, patients are unlikely to have early stage disease; therefore, we recommend using the following criteria to identify high-risk individuals examined by low-dose (LD) spiral chest computed tomography (CT) (LDCT) not only when they complain of symptoms but also at the annual physical examination in asymptomatic, high-risk patients 14 [grade 1C (Grading of Consensus are defined as the followings: Grade 1A: Strong recommendation, high-quality evidence; Grade 1B: Strong recommendation, moderate-quality evidence; Grade 1C: Strong recommendation, low-quality evidence; Grade 2A: Weak recommendation, high-quality evidence; Grade 2B: Weak recommendation, moderate-quality evidence; Grade 2C: Weak recommendation, low-quality evidence)]: 1. Between ages 55 and 80 years; 2. >20 Pack-years of tobacco smoking; 3. A history of high-risk occupational exposure; 4. A personal history of malignancy or a family history of lung cancer; and 5. A history of COPD, diffuse pulmonary fibrosis, or pulmonary tuberculosis. Because Chinese smoking rates, environmental factors, and chronic lung disease incidence are different from those in Western countries, the age range of patients for LDCT for lung cancer may be adjusted according local factors (grade 2C). Note that, because the ages of participants in clinical studies of LDCT lung cancer screening differ, currently, the lower age limit for screening is still controversial. Because the incidence of lung cancer differs in each province in China, physicians in the areas with high lung cancer incidence can adjust the lower age limit for lung cancer screening according to local epidemiologic information. Vigilance for lung cancer-related symptoms and physical signs Most early lung cancers occur without symptoms and signs; when the following clinical manifestations appear, patients generally are unlikely to have early stage disease, so clinicians should be alert to the possibility of lung cancer: 1. Persistent cough, with or without sputum; 2. Bloody sputum or hemoptysis; 3. Shortness of breath or wheezing (fixed wheeze can be auscultated); 4. Fever unresponsive to antibiotic treatment; 5. Weight loss; 6. Extrapulmonary manifestations, such as finger (or toe) clubbing, nonmigratory pulmonary arthralgia, hyperplasia of male mammary glands, tanned or dermatomyositis, and ataxia; and 7. Signs of local invasion and metastases, such as vocal cord paralysis, superior vena cava obstruction 3158 Cancer September 1, 2015

3 China Consensus on Lung Cancer Diagnosis/Hu et al TABLE 1. Technical Parameters of Low-Dose Computed Tomography Total radiation exposure 5 msv kvp 120 mas 60 Gantry rotation speed 0.5 s Detector collimation 1.5 mm Slice width 3 mm, 1.5 mm preferred Slice interval Slice width, 50% overlap preferred for 3D or CAD application Scan acquisition time 10 seconds Breathing Maximum inspiration Contrast No contrast CT scanner detectors 16 Abbreviations: 3D, 3-dimensional; CAD, computer-aided diagnosis; CT, computed tomography; kvp, kilovolts peak; msv, millisieverts. syndrome, Horner syndrome, Pancoast syndrome, or supraclavicular lymph node enlargement. Noninvasive Examinations Imaging examinations Chest x-ray. The advantages of chest x-ray examinations include availability, convenience, and low radiation exposure. Chest x-rays have certain limitations in early lung cancer detection, including difficulty detecting small lesions or lesions located areas of the lung that are poorly visualized on plain radiographs. Because of these limitations, the chest radiograph with or without sputum cytology examination is not recommended for lung cancer screening (grade 1A). 15 Chest CT. Chest CT is an important method for the detection lung cancer. It can identify the location of the lesion and the degree of involvement and can provide an important reference for distinguishing between benign and malignant lesions. Spiral LDCT of the chest can effectively detect lung cancer at an early stage, and it has been gradually replacing the x-ray, providing a more sensitive assessment tool for the diagnosis of pulmonary nodules. However, enhanced chest CT examination by intravenous injection of contrast enhancement with a standard radiation dose should be conducted when lung cancer is highly suspected or already diagnosed. CT-guided percutaneous lung biopsy is valuable for obtaining cytologic and histologic diagnoses. LDCT can detect more nodules (including early cancer) than plain chest x-ray. National Lung Screening Trial results demonstrated that, compared with chest x- ray screening, LDCT screening can reduce lung cancer mortality by 20%. LDCT has high resolution; it eliminates the problem of overlapping structures, so the detection rate of small lesions and early lung cancer is significantly higher than that in plain chest radiographs. Other advantages include lower potential radiation doses and less costly tubes and detectors. However, the image quality of LDCT is inferior to that of conventional CT, especially because the noise level increases with decreasing radiation dose, which makes it difficult to detect and differentiate nodules. A reasonable standard follow-up plan should be developed and strictly followed for patients who have positive LDCT screening results to minimize the false-positive rate of LDCT and subsequent invasive diagnostic techniques. We recommend applying the same technical parameters for both baseline and follow-up CT scans (Table 1) and standardized CT reporting, which is described in detail below (grade 1A). Pulmonary nodules detected by LDCT should be described in terms of location (lobe, segment, subpleural, etc), size (measured in the greatest dimension; nodule volume can be calculated in some hospitals if proper analysis software is available), density (solid/mixed/ground-glass opacity), calcification (with or without, central or eccentric, popcorn concentric ring/dot/dispersion), shape (round/oval/sheet/irregular), edge (smooth/leaf/burr), and annotation of the layer number of the nodule. For patients who have results from previous examinations, comparisons need to be made with the historic image to determine any obvious change, lesion stability time, and differences in the number of nodules, size, and density between the current nodules and the baseline image. Positron emission tomography/ct. Positron emission tomography/ct is helpful for the noninvasive diagnosis of benign and malignant nodules and can also provide important reference points with which to select lesions for biopsy. Biopsies of lesions with high metabolism are more likely to confirm a diagnosis of lung cancer. However, positron emission tomography/ct is not recommended as a routine screening examination, because the diagnostic value is limited for lesions <5 mm or for lesions with ground-glass opacity (grade 1C). Ultrasound. For lung lesions adjacent to or in the chest wall, ultrasound can identify the lesions as liquid or solid and can be used to guide the biopsy. Magnetic resonance imaging. Magnetic resonance imaging is superior for localizing relations between tumors and large blood vessels and can identify brain parenchyma or meningeal metastasis. However, magnetic resonance imaging is less sensitive than CT for small (<5 mm) pulmonary lesions. Cancer September 1,

4 Blood tumor biomarker analysis Blood tumor biomarker analysis is not routinely performed, because there are no specific lung cancer biomarkers used in clinical diagnosis. The following combination of examinations could be used for lung cancer diagnosis or for evaluating treatment effectiveness; a progressive increase in should prompt further evaluation (grade 1C). Progastrin-releasing peptide. Progastrin-releasing peptide is the preferred marker for diagnosing small cell lung cancer. Neuron-specific enolase. Neuron specific enolase is used for the diagnosis and therapeutic monitoring of small cell lung cancer. Carcinoembryonic antigen. Carcinoembryonic antigen measurement is mainly used to determine the prognosis of patients with lung cancer and to monitor the treatment process. Cytokeratin 19 fragment Cytokeratin 19 fragments are used in the diagnosis of squamous cell carcinoma of the lung with certain sensitivity and specificity. Squamous cell carcinoma. Squamous cell carcinoma antigen has a certain value in monitoring the treatment effectiveness of squamous cell carcinoma of the lung and predicting the disease prognosis. Sputum cytology Sputum cytology is currently 1 of the simplest and most convenient noninvasive methods of lung cancer diagnosis. The morning sputum is collected for 3 consecutive days and made into cytology smears, which are used to obtain a diagnosis. Liquid-based cytology can improve the diagnosis rate. High-quality sputum specimens and optimized specimen processing are important to improve the diagnostic ability of cytology. Invasive Examination Endoscopy Fiberoptic bronchoscopy. This is the most commonly used method for the diagnosis of lung cancer and includes techniques such as bronchoscope brushing, biopsy, fluoroscopy-guided transbronchial lung biopsy (TBLB), and bronchial washing to obtain cytologic and histologic diagnoses. Combining these methods can improve the detection rate. Bronchoscopy is helpful for establishing a diagnosis, determining the surgical field, and identifying clear indications for surgery. The diagnosis rate of brushing can reach 92%, and the biopsy diagnosis rate is 93% for endobronchial lesions that are visible on bronchoscopy. The disadvantages of bronchoscopy include smaller biopsy specimens, the difficulty of reaching malignant cells in deep submucosal lesions using biopsy forceps, and the rate of false-negative results. Combining brushing with transbronchial needle aspiration can improve the diagnosis rate. Transbronchial fiberoscopic lung biopsy can improve the diagnosis rate of peripheral lung cancers. For lesions that measure >4 cm in greatest dimension, the diagnosis rate can reach 50% to 80%. However, for lesions that measure <2 cm in greatest dimension, the diagnosis rate is only approximately 20%. Bronchoscopy complications are rare; the most common complications include laryngeal spasm, pneumothorax, hypoxemia, and bleeding. Pulmonary artery hypertension, hypoxemia with carbon dioxide retention, and a tendency to bleed should be considered contraindications to lung biopsy. 15 Fluorescence bronchoscopy. For early central lung cancer, especially small lesions that are difficult to detect on CT imaging, fluoroscopy can provide real-time image acquisition and can detect the tracheal bronchus mucosa in the small area of fluorescent changes. Biopsy of the tracheobronchial tree regional mucosa in the area of abnormal fluorescence can increase the detection of premalignant lesions in small (atypical hyperplasia) or early (carcinoma in situ) malignancies. Previous research indicates that the combined use of exfoliated sputum cells and fluorescence bronchoscopy examination is an effective means of early central lung cancer detection. Ultrasound bronchoscopy. Fiber ultrasonic bronchoscope-guided transmural lymph node biopsy (endobronchial ultrasound [EBUS]-transbronchial needle aspiration) helps to identify mediastinal lymph node involvement, airway wall infiltrates, and extraluminal lesions and can also provide effective lung cancer TNM staging of lymph nodes. Peripheral ultrasonic bronchoscopy. The observation of peripheral lung lesions with a peripheral ultrasonic probe and guided lung biopsy in EBUS-TBLB provides more accurate positioning than traditional TBLB technology, especially for peripheral pulmonary nodules, and can further improve the positive biopsy rate. The radial ultrasonic probe can provide a real-time imaging illustration of peripheral lung lesions and guided lung biopsy (EBUS- TBLB). Ultrasonic bronchoscope technology is recommended for use in any hospital that has the technology Cancer September 1, 2015

5 China Consensus on Lung Cancer Diagnosis/Hu et al Thoracoscopy. Thoracoscopy can be used to accurately diagnose and stage lung cancer, especially small, nodular lung lesions for which TBLB or percutaneous pulmonary biopsy needle aspiration biopsy (transthoracic needle aspiration [TTNA]) are unable to obtain pathologic specimens that are sufficient for diagnosis. For locally advanced lung cancer, thoracoscopy can provide cytology samples from lymph nodes as well as pleural and pericardial effusions. Mediastinoscopy. Mediastinoscopy is an effective method for diagnosing lung cancer and staging lymph nodes, and it is the current gold standard for the clinical evaluation of mediastinal lymph node involvement in lung cancer; it can also compensate for the inadequacy of EBUS. Other technology Percutaneous pulmonary biopsy needle aspiration biopsy. TTNA can be performed with CT or ultrasound guidance and has both higher sensitivity and specificity in the diagnosis of peripheral lung cancer. Lesions near the chest wall can be accessed with ultrasound-guided aspiration biopsy. Lesions that are not close to the chest wall can be reached with x-ray guided or CT-guided percutaneous needle aspiration or biopsy. Because needle biopsy collects a limited number of cells, it may produce false-negative results. To improve the diagnostic rate, multiple repeated samples are recommended. Approximately 29% of lesions are negative based on initial cytology, whereas repeated inspection yields a few malignant cells. A common complication of percutaneous needle aspiration cytologic examination is pneumothorax, with an incidence rate of approximately 25% to 30%. Lung compression <25% is often self-absorbed, whereas larger pneumothoraces may require thoracic extraction or chest tube drainage. Thoracentesis and pleural biopsy. When the causes of pleural effusion are unknown, pleural puncture can be performed to obtain the cytologic diagnosis, determine lung cancer staging, exclude nonmalignant pleural effusions, and determine whether surgery is needed. When multiple thoracentesis and pleural effusion examinations do not reveal the etiology, pleural biopsy can improve the positive detection rate. Before invasive examinations, such as bronchoscopy, percutaneous lung biopsy, thoracoscopy, or mediastinoscopy, it is important to assess the patient s cardiopulmonary function by pulmonary function testing, electrocardiography, and echocardiography to clarify the indications and contraindications for the procedure. The effective treatment of underlying chronic heart or lung disease and the control of symptoms should be achieved before the patient s next preoperative evaluation. During this process, electrocardiogram, blood oxygen saturation, and blood pressure should be monitored. For each of the above-mentioned examinations and indications, please refer to the relevant guidelines and contraindications. Early Diagnosis of Lung Cancer Lung cancer diagnosis (grade 1A) Histopathologic diagnosis is mandatory for the diagnosis and treatment of lung cancer. Immunohistochemistry staining is recommended for further identification of the histopathologic subtype. If the pathology diagnosis cannot be determined because of inadequate sample size, then we suggest that clinicians repeat the biopsy or combine it with imaging examinations when necessary. To provide specific information for individualized treatment, we also suggest performing parallel investigations for epidermal growth factor receptor (EGFR) gene mutations, anaplastic lymphoma kinase (ALK) fusion genes, and c- Ros oncogene 1 (ROS1) fusion genes to achieve a molecular pathologic diagnosis in patients with non-small cell lung cancer. Lung cancer diagnosis and staging refer to the seventh edition of the TNM staging system released by International Association for the Study of Lung Cancer (IASLC) in July Differential diagnosis It is necessary to differentiate primary lung cancer from tuberculosis, pulmonary fungal diseases, benign tumors, metastatic tumors, and other diseases. Serum analysis of tuberculosis and fungi can sometimes provide the necessary information for differential diagnosis (grade 2A). For the patients in whom infectious diseases cannot be excluded, we suggest anti-infectious treatment with follow-up chest CT scans (grade 2C). Imaging Evaluation of Pulmonary Nodules For the evaluation of benign and malignant nodule images, see Table 2 (grade 1A). Follow-up period (grade 1B) Follow-up imaging should provide adequate imaging data while reducing the radiation dose as much as possible; therefore, decisions regarding follow-up frequency and duration in patients with pulmonary nodules should consider the nodule size and properties as well as surgical feasibility and risk factors for lung cancer. The size, properties, and numbers of nodules should be followed on initial detection. Bidimensional measurements of oval Cancer September 1,

6 TABLE 2. Imaging Evaluation of Benign and Malignant Pulmonary Nodules Risk Factors of Malignant Nodules Less Likely Possible Highly Malignant Greatest nodule dimension, mm < >20 Age, y < Personal history None <20 Pack-year smoking history or 20 pack-year smoking history and 15 year smoking cessation 20 Pack-year smoking history; lung cancer family history; chronic pulmonary diseases history Nodules Round, smooth margin; central calcification Unsmoothed margin, ground-glass density Lobulated and/or speculated margin, solid or mixed density Figure 1. This is the diagnostic algorithm for undetermined lung nodules in operable nonsmokers. lesions or the 3-dimensional reconstruction of the nodule imaging may provide additional information for helping to determine the diagnosis strategy. In patients with multiple nodules, the follow-up period should abide by the biggest nodule. The recommendations below only pertain to patients who have incidentally detected nodules without a known primary extrathoracic malignancy In patients without lung cancer risk factors and with surgical indications, the frequency of CT follow-up should be as follows: 1. For nodules 4 mm, LDCT follow-up every year; 2. For nodules >4 mm but <6 mm, follow-up at 12 months; if there is no change, then follow-up once annually; 3. For nodules >6 mm but <8 mm, 6-month to 12- month follow-up; if there is no change, then 18-month to 24-month subsequent follow-up; and 4. For nodules >8 mm, if there is no change, then follow-up at the traditional frequency of 3, 6, 12, and 24 months. This process is illustrated in Figure 2. For patients who have 1 or more risk factors for lung cancer and the possibility of surgery, the frequency of CT should depend on the nodule density and the size of the different processes, as illustrated in Figure 2. Duration of follow-up (grade 1B) It has been demonstrated that some malignant lesions, such as ground-glass nodules and partial solid nodules, have longer doubling times. Therefore, after completion of the first 2 years of follow-up, if the lesion is stable both in size and in density, then we still suggest annual LDCT inspection unless the patient is unable to tolerate the recommended anticancer treatment because of age or uncontrolled severe comorbidities. If the baseline examination revealed lung cancer or diseases other than lung nodules, such as COPD or coronary artery calcification, then further diagnosis, treatment, and follow-up are needed for the related diseases We suggest further biopsy and treatment if any of the following circumstances suggest that nodular growth occurred on CT during follow-up: the greatest dimension of the baseline nodule is 15 mm compared with increases of 2 mm in the baseline greatest dimension; the greatest dimension of the baseline nodule is >15 mm compared with increases >15% in the greatest dimension 3162 Cancer September 1, 2015

7 China Consensus on Lung Cancer Diagnosis/Hu et al Figure 2. This is the diagnostic algorithm for undetermined lung nodules in the operable high-risk population. CT indicates computed tomography; FU, follow-up; m, month(s); PET, positron emission tomography. of the baseline nodule; an increase in pure ground-glass density, or the appearance of solid ingredients, or an increase in the solid component of original mixed-density nodules; or the emergence of new pulmonary nodules. If the baseline CT examination reveals tracheal or bronchial wall thickening, luminal stenosis, or intraluminal nodules, then we suggest bronchoscopy, and conditional examinations can be performed using fluorescence bronchoscopy. Note that the consensus on lung nodule follow-up strategy was updated in more detail in Chinese Consensus on the Diagnosis of Lung Nodules (2015) drafted by the Lung Cancer Study Group of the Chinese Thoracic Society and the Chinese Alliance Against Lung Cancer Expert Group. 21 According to the updated consensus, in patients without lung cancer risk factors who have nodules <4 mm, the decision whether or not to follow patients should be made individually, based mainly on the imaging characteristics of the nodules. Patients should be well informed of the potential advantages and the risks of follow-up LDCT studies. In patients without lung cancer risk factors who have nodule between 4 mm and 6 mm in greatest dimension, the recommendation is to follow-up after an assessment of malignancy, possibly using several specific criteria. Application of a minimally invasive biopsy technique (grade 1A) 1. In patients with persistent cough, unexplained hemoptysis, large airway, or pulmonary hilar lesions on CT, sputum cytology and fiber bronchoscopy examinations are needed. Hospitals that have fluorescence or ultrasonic bronchoscopes could conduct further examinations to yield a better diagnosis rate For those with pulmonary nodules >8 mm, if the lesions can be revealed under fluorescence, then it is feasible for the patient to undergo TBLB or a combination of peripheral ultrasound bronchoscopy and magnetic navigation system-assisted positioning biopsy; if the lesions are located in the peripheral lung, then CTguided percutaneous lung biopsy can be performed; for pleural lesions, ultrasound-guided percutaneous lung puncture is feasible. Cancer September 1,

8 3. For those without surgical contraindications, thoracoscopy is the last choice for the diagnosis and treatment of progressive pulmonary lesions that are undiagnosed by the technologies mentioned above. Multidisciplinary Cooperation (Grade 1A) The early detection of lung cancer requires effective communication and close multidisciplinary cooperation among departments of respiratory diseases, thoracic surgery, medical imaging, and pathology. For patients who have undetermined lung lesions or lesions that are highly suggestive of cancer after a follow-up imaging examination, bronchoscopy, or percutaneous lung biopsy, a multidisciplinary discussion is necessary to develop further diagnostic strategy. In patients with lung cancer, we need to study the disease history; carefully analyze the results from invasive and noninvasive examinations; and, combined with epidemiology, risk assessment, and the patients indications for surgery, formulate a reasonable and scientific diagnostic strategy to differentiate between benign and malignant lung lesions. FUNDING SUPPORT This work was primarily supported by the National Key Scientific and Technology Support Program: Collaborative Innovation of Clinical Research for Chronic Obstructive Pulmonary Disease and Lung Cancer (2013BAI09B09). CONFLICT OF INTEREST DISCLOSURES The authors made no disclosures. REFERENCES 1. Bender E. Epidemiology: The dominant malignancy. Nature. 2014; 513(7517):S2-S3. 2. Lin BQ, Peto R, Chen ZM, et al. Emerging tabacco hazards in China:Retrospective proportional mortality study of one million deaths. BMJ. 1998;317(7170): Bai CX. The current status and controversy of lung cancer screening. In: Wang C, ed. Respiratory and Intensive Medical Care. Beijing, China: People s Medical Publishing; 2012: Bai CX. Three plus two diagnoses method for lung nodules. Int J Respir. 2013;33(6): Jemal A, Thun MJ, Ries LA, et al. Annual report to the nation on the status of cancer, , featuring trends in lung cancer, tobacco use, and tobacco control. J Natl Cancer Inst. 2008;100: Moolgavkar SH, Holford TR, Levy DT, et al. Impact of reduced tobacco smoking on lung cancer mortality in the United States during J Natl Cancer Inst. 2012;104: Lubin JH, Boice JD Jr. Lung cancer risk from residential radon: metaanalysis of 8 epidemiologic studies. J Natl Cancer Inst. 1997;89: Darby S, Hill D, Auvinen A, et al. Radon in homes and risk of lung cancer: collaborative analysis of individual data from 13 European case-control studies [serial online]. BMJ. 2005;330: Matakidou A, Eisen T, Houlston RS. Systematic review of the relationship between family history and lung cancer risk. Br J Cancer. 2005;93: Mayne ST, Buenconsejo J, Janerich DT. Previous lung disease and risk of lung cancer among men and women nonsmokers. Am J Epidemiol. 1999;149: Skillrud DM, Offord KP, Miller RD. Higher risk of lung cancer in chronic obstructive pulmonary disease. A prospective, matched, controlled study. Ann Intern Med. 1986;105: Koshiol J, Rotunno M, Consonni D, et al. Chronic obstructive pulmonary disease and altered risk of lung cancer in a population-based case-control study [serial online]. PLoS One. 2009;4:e Turner MC, Chen Y, Krewski D, et al. Chronic obstructive pulmonary disease is associated with lung cancer mortality in a prospective study of never smokers. Am J Respir Crit Care Med. 2007;176: National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Lung Cancer Screening, Version Fort Washington,PA:NCCN;2016version1.Availableat: org/professionals/physician_gls/pdf/lung_screening.pdf 15. Zhi XY, Wu YL, Bu H, et al. Lung Cancer Diagnosis and Treatment Expert Panel of the Chinese Ministry of Health. Chinese guidelines on the diagnosis and treatment of primary lung cancer. J Thorac Dis. 2012;4: Wender R, Fontham ET, Barrera E Jr, et al. American Cancer Society lung cancer screening guidelines. CA Cancer J Clin. 2013;63: Peters S, Adjei AA, Gridelli C, Reck M, Kerr K, Felip E; ESMO Guidelines Working Group. Metastatic nonsmall-cell lung cancer (NSCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(suppl 7):vii56-vii Field JK, Smith RA, Aberle DR, et al. IASLC CT Screening Workshop 2011 Participants. International Association for the Study of Lung Cancer Computed Tomography Screening Workshop 2011 report. J Thorac Oncol. 2012;7: Klabunde CN, Marcus PM, Han PK, et al. Lung cancer screening practices of primary care physicians: results from a national survey. Ann Fam Med. 2012;10: Nair A, Hansell DM. European and North American lung cancer screening experience and implications for pulmonary nodule management. Eur Radiol. 2011;21: Lung Cancer Study Group of the Chinese Thoracic Society and the Chinese Alliance Against Lung Cancer Expert Group. Chinese consensus on diagnose of lung nodules. Zhonghua Jie He He Hu Xi Za Zhi. 2015;38(4): Cancer September 1, 2015