Criteria for lung cancer screening and standardized management in China

According to the latest Report of Cancer Epidemiology in China,[1] published by the National Cancer Center (NCC), lung cancer is the malignancy with the highest incidence in China (57.26/100,000). We have developed the Evaluation of Pulmonary Nodules: Clinical Practice Consensus Guidelines for Asia,[2] and the Chinese Expert Consensus on the Diagnosis and Treatment of Pulmonary Nodules.[3] To enhance the early diagnosis of lung cancer and improve the prognosis, we also developed the Chinese Expert Consensus on the Screening and Management of Lung Cancer.[4] However, challenges remain in clinical practice, therefore, the Chinese Alliance Against Lung Cancer (CAALC) invited clinical, information technology (IT), and health economics experts to discuss these issues, and drafted this document, Criteria for Lung Cancer Screening and Standardized Management in China.[5] Selection of the Population for Lung Cancer Screening Concerning the selection criteria for the population to be screened for lung cancer in China, local conditions should be taken into full consideration. Therefore, both the international consensus/guidelines and China's actual situation should be considered when defining the populations at high risk for lung cancer. The high-risk population for lung cancer in China is defined as adults aged 40 years and older with any of the following risk factors: (1) a smoking history with a smoking index ≥400 (or 20 pack-years) and current smoker or having quit smoking within the past 15 years; (2) a history of environmental or occupational exposure to carcinogens; (3) the presence of chronic obstructive pulmonary disease (COPD), diffuse pulmonary fibrosis, or a history of pulmonary tuberculosis (TB); (4) a history of malignant tumors or a family history of lung cancer. Additional factors such as passive smoking and air pollution should also be assessed. (Supplementary Table 1, https://links.lww.com/CM9/B589). Selection of the Technology for Lung Cancer Screening Currently, there is no single approach that can meet all requirements, and it is necessary to make reasonable choices based on the individuals to be screened and the accessibility of the technologies [Supplementary Figure 1, https://links.lww.com/CM9/B589]. Sputum cytology: New testing methods have been developed, including the liquid-based thinprep cytologic test (TCT), and the sputum sediment section examination based on double embedding.[6] Another innovative technology was called LuCED. Nevertheless, due to its limitations, sputum cytology should not be applied as the dominant screening method. Imaging: Low-dose computed tomography (LDCT) is recommended as a reliable, fundamental method for lung cancer screening in the populations at high risk. By applying artificial intelligence (AI) in-depth mining of data, it is feasible to acquire more specific information of pulmonary nodules. Positron emission tomography combined with computed tomography (PET-CT) has a fairly high clinical value in the diagnosis, staging, and treatment evaluation of lung cancer.[7] However, the positive detection rate of PET-CT is not high for lung cancer nodules measuring less than 8 mm in diameter. Therefore, PET-CT is not recommended as a routine method for initial screening. Bronchoscopy: Bronchoscopy cannot be used for routine screening. However, studies have shown that it can be applied for screening in long-term heavy smokers at high risk for central squamous cell carcinoma. Autofluorescence bronchoscopy (AFB) testing is suitable for the screening of early-stage central lung cancer, especially in cases with small lesions in the bronchial lumen, which are difficult to detect by CT, and in patients who have malignant cells in sputum but lesions are not found on white light bronchoscopy (WLB). Fibered confocal fluorescence microscopy (FCFM) is a newly developed technique, which can accurately detect metaplasia of bronchial epithelium, dysplasia, carcinoma in situ (CIS), and invasive carcinoma.[8] Nevertheless, the operator needs to have experience in using bronchoscope, and the cost is high. Biomarkers: At present, the commonly used biomarkers are[9]: (1) progastrin-releasing peptide (ProGRP); (2) neuron specific enolase (NSE); (3) carcino-embryonic antigen (CEA); (4) cytokeratin 19 fragment (CYFRA21-1); and (5) squamous cell carcinoma antigen (SCC-Ag). Lung tumors can trigger host immune responses and elicit antibodies against tumor antigens called tumor-associated autoantibodies (TAAbs). The term "circulating tumor cells" (CTCs) refers to intact cells that shed from primary tumors into the bloodstream via the venous system or the lymphatic system. CTCs can replace or partly replace tissue samples for the diagnosis of diseases, molecular sequencing, dynamic monitoring of tumor changes, and evaluation of prognosis. Circulating genetically abnormal cells (CACs) are cells with tumor-specific chromosomal loci in the peripheral blood. CACs containing similar genetic abnormalities to the primary tumor are present in patients with non-small cell lung cancer staged from I through IV, and the number of CACs correlates with disease recurrence and survival rates.[10] Artificial intelligence (AI)-Assisted Lung Cancer Screening and Quality Control Requirements for clinical information:(1) Smoking history, family history of tumors, occupational dust exposure history, COPD history, etc.; (2) CT images: thin-layer CT of 1 mm saved in DICOM format. Data processing : (1) Automatic extraction of the patients' clinical information; (2) intelligent collection of clinical information in different settings; (3) identification of medical records and mapping with terminology standards. Statistical analysis and quality control : Quality control helps hospitals and doctors to achieve a level of homogeneous management in line with national and departmental standards throughout the disease process. Security: (1) Evaluation of the system safety and protection measures; (2) evaluation of data security; (3) evaluation of user identity management; (4) evaluation of user privacy protection. Performance indicators: (1) Document review; (2) technical tests: including (a) the maximum acceptable concurrency and the response time of the system; (b) the efficiency in data process. Standardization of Lung Cancer Screening and Management Screening and management strategy: Improving participation is the foundation of lung cancer screening and patient management. Once pulmonary nodules are detected, regular follow-ups should be arranged. Initial assessment : In the initial assessment, the collection of clinical information and CT images is the most important factor. Tests for TB, fungal infections, and tumor biomarkers are also required for differential diagnosis. Clinical judgement: Cases with pulmonary nodules measuring about 10 mm or less in diameter are difficult to diagnose in the initial assessment, and tend to require clinical judgement or further analysis by AI. For those for whom tumors cannot be excluded and who are also not fit for biopsies, a personalized CAC test is recommended. PET-CT should be considered for those for whom multiple pulmonary nodules resulting from metastatic lung tumors cannot be excluded, or with pulmonary nodules measuring more than 8 mm in diameter, or who are in need of personalized preoperative management. The article introduces the high-risk groups for lung cancer screening considering the local conditions in China and the pros and cons of some screening approaches for lung cancer. Medical internet of thing (MIoT)-based applications can facilitate health education for patients to encourage their participation in screening, and provide assistance with accurate management. It is also necessary to thoroughly study the authoritative consensus/guidelines, integrate the know-how into the doctors' workflows, and make the best use of the data from the hospitals' information systems to develop a system that can assist doctors in their clinical decisions, as well as to ensure an effective quality control, in order to reach homogeneous diagnosis and treatment levels that meet national standards. Expert Group of Criteria for Lung Cancer Screening and Standardized Management in China (Sort by surname alphabetically) Chong Bai (Changhai Hospital Affiliated to Second Military Medical University); Li Bai (Xinqiao Hospital, Army Medical University); Chunxue Bai (Shanghai Institute of Respiratory Diseases, Zhongshan Hospital Fudan University); Zhigang Cai (The Second Hospital of Hebei Medical University); Chengshui Chen (The First Affiliated Hospital of Wenzhou Medical University); Gang Chen (The Third Hospital of Hebei Medical University); Hong Chen (The Second Affiliated Hospital of Harbin Medical University); Liang'an Chen (Chinese People's Liberation Army General Hospital); Shuliang Guo (The First Affiliated Hospital of Chongqing Medical University); Chengping Hu (Central South University Xiangya Hospital); Jian'an Huang (The First Affiliated Hospital of Suzhou University); Faguang Jin (Tangdu Hospital of Fourth Military Medical University); Ming Li (Huadong Hospital Affiliated to Fudan University); Qiang Li (Shanghai General Hospital); Shiyue Li (Guangzhou Institute of Respiratory Diseases); Weimin Li (West China Hospital of Sichuan University); Yong Song (Nanjing General Hospital of Nanjing Military Command); Jiayuan Sun (Shanghai Chest Hospital); Mengting Sun (Zhongshan Hospital Fudan University); Lin Tong (Zhongshan Hospital Fudan University); Jianlin Wu (Affiliated Zhongshan Hospital of Dalian University); Guangfa Wang (Peking University First Hospital); Hongwu Wang (Dongzhimen Hospital of Beijing University of Chinese Medicine); Kai Wang (The Fourth Affiliated Hospital of Zhejiang University School of Medicine); Qi Wang (The Second Hospital of Dalian Medical University); Yuehong Wang (The First Affiliated Hospital, Zhejiang University School of Medicine); Xueling Wu (Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine); Baosong Xie (Fujian Provincial Hospital); Jianwei Xuan (School of Pharmacy, Sun Yat-sen University); Kui Xiao (The Second Xiangya Hospital of Central South University); Tao Xu (Affiliated Hospital of Qingdao University); Hongyi Xin (University of Michigan—Shanghai Jiao Tong University Joint Institute); Xinying Xue (Beijing Shijitan Hospital Affiliated to Capital Medical University); Shuanying Yang (The Second Affiliated Hospital of Xi'an Jiaotong University); Dawei Yang (Zhongshan Hospital Fudan University); Yiming Zeng (The Second Affiliated Hospital of Fujian Medical University); Guozhen Zhang (Huadong Hospital Affiliated to Fudan University); Jian Zhang (Xijing Hospital of Fourth Military Medical University); Jie Zhang (Beijing Tiantan Hospital Affiliated to Capital Medical University); Li Zhang (Peking Union Medical College Hospital); Lichuan Zhang (Affiliated Zhongshan Hospital of Dalian University); Min Zhang (Shenzhen Second People's Hospital); Xiaoju Zhang (Henan Provincial People's Hospital); Chengzhi Zhou (Guangzhou Institute of Respiratory Diseases); Jian Zhou (Zhongshan Hospital Fudan University); Jianying Zhou (The First Affiliated Hospital, Zhejiang University School of Medicine); Hong Zhou (Huawei Research Institute); Yu Zhu (East China University of Science and Technology); Xiaoli Zhu (Zhongda Hospital Southeast University). Funding This study was supported by grants from the Science and Technology Commission of Shanghai Municipality (Nos. 20DZ2254400, 21DZ2200600, and 20DZ2261200). Conflicts of interest None.