Lung Cancer in People’s Republic of China

As of 2018, the People’s Republic of China was the most populous country in the world, reaching a total population of approximately 1.39 billion people, of which about 831 million and 564 million people lived in urban and rural regions, respectively. The 2020 population is estimated to be 1.44 billion, remaining the largest in the world. Owing to the country’s large population and rapid socioeconomic development, cancerr epresents a significant health, financial, and societal burden. Lung cancer is the leading cause of cancer-related morbidity and mortality in the People’s Republic of China and has been increasing over the past decades. This creates a huge challenge for the Chinese government, health management department, and professional specialists in lung cancer. Many efforts have been undertaken to address this issue, including favorable policies for screening, effective measures, the People’s Republic of China–specific programs on cancer prevention, screening, improvements in medical insurance, treatment advances, and creation of incentives for clinical research. This editorial will discuss the current scientific knowledge and diagnostic and treatment paradigms of lung cancer in the People’s Republic of China. The Chinese government has established a multilevel medical security system that includes the universal health care system (by the national agency), commercial medical insurance (by commercial insurance organizations), and a medical charity aid (by charity institutions) to achieve the goals that “everyone will have access to health care” and “poor people can afford the medical costs.” Chinese health care applies a universal system that comprises basic medical insurance, urban and rural medical assistance, serious illness aid, and critical illness insurance. Payment of health care costs is associated with the patients’ medical insurance type. The People’s Republic of China accounts for one-fifth of the world’s population and is currently facing unprecedented challenges in cancer control and prevention with rapid socioeconomic development and an increasingly aging population. The government has recognized the importance of this problem and has implemented a series of strategies including developing a systematic cancer surveillance network and conducting cancer prevention and control programs. The National Cancer Registration and Follow-up Programme was launched by the Ministry of Health of the People’s Republic of China in 2008, and the number of cancer registries increased from 95 in 2008 to 574 in 2019. The National Central Cancer Registry of the People’s Republic of China is responsible for data collection, evaluation, and publishing of national cancer statistics. Cancer statistics were updated by the National Central Cancer Registry on the basis of data from 368 qualified cancer registries. It was estimated that the total number of newly diagnosed cases of lung cancer in the People’s Republic of China in 2015 was about 787,000, corresponding to over 2100 new lung cancer diagnoses each day. Lung cancer accounted for about 20% of all cancer diagnoses, and the age-standardized incidence rate by world standard population was estimated to be 35.92 per 100,000 in the country in 2015 (Table 1). The age-standardized incidence rates of lung cancer for male and female populations were 48.87 and 23.52 per 100,000, respectively, which represented 520,300 male and 266,700 female individuals diagnosed each year. The urban areas had a lower age-standardized incidence rate for lung cancer for the male population than the rural areas, whereas the opposite was true for the female population (24.17 and 22.61 per 100,000 in urban areas and in rural areas, respectively). The age-specific lung cancer incidence rate was relatively low below the age of 40 and increased dramatically after that, reaching a peak in the age group of 80 to 84 years, both in male and female populations. Before then, the incidence rates were significantly lower in female individuals than in male individuals (Fig. 1).Table 1Lung Cancer Incidence and Mortality in the People’s Republic of China, 2015AreaSexIncidenceMortalityCasesProp. (%)ASIR (1/105)RankDeathsProp. (%)ASMR (1/105)RankAll areasBoth sexes787,00020.035.921630,50027.028.021Male population520,30024.248.871433,20029.340.111Female population266,70015.023.522197,30023.016.541Urban areasBoth sexes460,20019.636.071365,90027.527.821Male population300,40023.948.521250,70030.039.851Female population159,80014.624.172115,20023.316.401Rural areasBoth sexes326,80020.735.681264,60026.328.251Male population219,90024.649.301182,50028.440.411Female population106,90015.622.61182,10022.616.731ASIR, age-standardized incidence rate using Segi’s population; ASMR, age-standardized mortality rate using Segi’s population; prop., proportion. Open table in a new tab ASIR, age-standardized incidence rate using Segi’s population; ASMR, age-standardized mortality rate using Segi’s population; prop., proportion. Regarding mortality, it was estimated that about 630,500 patients with lung cancer died in 2015, which is equivalent to an average of over 1700 deaths each day. Lung cancer accounted for 27% of the mortality of all sites combined, and the age-standardized mortality rate was estimated to be 28.02 per 100,000 in the People’s Republic of China in 2015. The numbers of lung cancer deaths were 433,200 and 197,300, with age-standardized rates for lung cancer mortality of 40.11 and 16.54 per 100,000 for the male and female populations, respectively. The rural areas had relatively higher age-standardized rates of lung cancer mortality (40.41 per 100,000) for male individuals than the urban areas (39.85 per 100,000). Age-specific mortality rates by sex and area are shown in Figure 2. The trend for lung cancer mortality in different age groups was similar to the trend for incidence. The economic growth and the increasingly urbanized and westernized lifestyle experienced in the country have resulted in increased environmental pollution. Outdoor air pollution, considered to be among the worst in the world, and indoor air pollution, through heating and cooking using coal and other biomass fuels, mean that the Chinese population is exposed to many environmental carcinogens. Nevertheless, the measured attributable risk for environmental pollution is low, and most lung cancer incidence and deaths can be attributed to smoking. The leading preventable cause of cancer death was active smoking in men.1Chen W. Xia C. Zheng R. et al.Disparities by province, age, and sex in site-specific cancer burden attributable to 23 potentially modifiable risk factors in China: a comparative risk assessment.Lancet Glob Health. 2019; 7: e257-e269Abstract Full Text Full Text PDF PubMed Scopus (123) Google Scholar According to the Global Adult Tobacco survey in the People’s Republic of China, the current smoking rate is about 26.6% of adults (about 50.5% of men and 2.1% of women smoke). Though the difference was not statistically significant (28.1% in 2010 and 26.6% in 2018), the overall current rate of tobacco smoking revealed a trend toward decrease from 2010 to 2018. Only 16.1% of current smokers plan to or are thinking about quitting in the next 12 months; however, over 90% of smokers who tried to quit in the past 12 months did not use any quitting assistance for at least one quit attempt. Tobacco control is one of the most important issues in lung cancer prevention and control in the People’s Republic of China (Fig. 3). Screening is conceptually a reliable strategy for reducing mortality in lung cancer. According to the findings from the National Lung Screening Trial, screening for lung cancer with low-dose computed tomography (LDCT) is the most effective way to reduce mortality in lung cancer.2Moyer V.A. U.S. Preventive Services Task ForceScreening for lung cancer: U.S. Preventive Services Task Force recommendation statement.Ann Intern Med. 2014; 160: 330-338Crossref PubMed Google Scholar During the past few decades, great efforts, regarding both organized and opportunistic lung cancer screening, have been made in the country. Two large-scale, population-based, organized lung cancer screening programs have been conducted across the country in recent decades in the context of the National Cancer Screening Programs funded by the National Health Commission. One is the Rural People’s Republic of China Screening Program (RuraCSP) initiated in 2010 among the rural population that is at high risk of developing cancer. Through the RuraCSP, lung cancer screening has been conducted in six provinces and about 13,000 high-risk individuals have been assessed by LDCT scan with a lung cancer detection rate of 1%.3Zhou Q. NELCIN B3 screening program in China.J Thorac Oncol. 2018; 13: S272-S273Abstract Full Text Full Text PDF Google Scholar For the general community population in the country, the Cancer Screening Program in the Urban People’s Republic of China (CanSPUC) was initiated since 2012.4Chen W. Li N. Shi J. et al.Progress of cancer screening program in urban China.China Cancer. 2019; 28: 23-25Google Scholar By the end of 2017, a total of 521,302 eligible participants were identified as being at high risk of lung cancer, of which 163,752 participants underwent LDCT screening. Follow-up of the CanSPUC is ongoing. To optimize the use of the limited health care resources, the following two-step process has been adopted in both RuraCSP and CanSPUC: screening that involves a relative risk assessment for lung cancer and subsequent LDCT scan for high-risk individuals. In addition to the national programs, several population-based, organized lung cancer screening programs were funded by the local governments, such as in Tianjin5Gao Z. Ye Z. Zhang P. Cui X. Xie Y. Han L. Low-dose computed tomography screening for lung cancer in Tianjin: a preliminary clinical analysis of baseline screening and follow-up results.Chin J Clin Oncol. 2017; 44: 1034-1039Google Scholar and Shanghai.6Luo Xiaoyang Liu Quan Wang Shengping et al.Shanghai community-based practice of early lung cancer screening with low-dose spiral computed tomography.Chin Oncol. 2016; 26: 996-1003Google Scholar Hospital-based opportunistic lung cancer screening with LDCT in the country has also been conducted. The main findings of the collaboration between the Cancer Hospital Chinese Academy of Medical Sciences and the International Early Lung Cancer Action Program revealed a lung cancer detection rate of 0.6% in 4690 asymptomatic participants aged 40 years or older, of which 76% of the cases were in the early stage (I and II).7Tang W. Wu N. Huang Y. et al.Results of low-dose computed tomography (LDCT) screening for early lung cancer: prevalence in 4 690 asymptomatic participants.Chin J Oncol. 2014; 36: 549-554Google Scholar Meanwhile, a series of opportunistic LDCT lung cancer screening studies conducted in Guangdong,8GJY Yanmei Exploration on application of low dose chest CT scan in screening early lung cancer in routine physical examination.China Med Pharm. 2019; 9: 137-139Google Scholar Beijing,9Zhang Chun-Fang Z.Q. Wei-Min W. Dan F. Yuan H.E. Detection rates and cost of lung cancer screening with low-dose helical computed tomography among physical examination people.Chin J Cancer Prev Treat. 2015; 22: 247-251Google Scholar Hebei,10Wang X. Low-Dose Computer Tomography Screening for Lung Cancer and the Differentiating Computer Tomography Features of Early Stage Lung Cancer [postgraduate thesis].2016Google Scholar Shanxi,11Wang Wei Nie Shu-Wei Li S-Q Xu Chang-Tai Diagnosis value of low-dose spiral CT for early lung cancer.Med Recapitulate. 2012; 18: 310-312Google Scholar and Shanghai12Zhang Y. Hong Q.Y. Shi W.B. et al.[Value of low-dose spiral computed tomography in lung cancer screening].Zhonghua yi xue za zhi. 2013; 93: 3011-3014PubMed Google Scholar are consistent in the conclusion that opportunistic lung cancer screening could increase the early detection rate of lung cancer. Nevertheless, identification of the high-risk population of lung cancer and the high false-positive rate of LDCT detection still pose challenges to the success and cost-effectiveness of lung cancer screening. Several studies have been supported by the Ministry of Science and Technology to address key issues in lung cancer screening. The study of the National Cohort of Lung Cancer was initiated in 2017 and aims to collect biosamples from a population at risk of lung cancer and patients with lung cancer for further research. The People’s Republic of China National Cancer Early Screening trial: lung and colorectal cancer began in 2019 and is the first population-based cancer screening randomized controlled trial in the country. It seeks to determine whether screening with LDCT could reduce lung cancer–specific mortality in Chinese urban residents who are at high risk of developing lung cancer. If there is a significant lung cancer–specific mortality reduction in screening groups, lung cancer–specific mortality between high-risk population receiving annual LDCT screening versus biennial LDCT screening will be compared. Currently, more than 10,000 people have been recruited in the People’s Republic of China National Cancer Early Screening trial. On the basis of the evidence of the above-mentioned programs, the People’s Republic of China National Cancer Center is currently preparing the national lung cancer screening guidelines for the country. There are many types of imaging that can be used for diagnosing lung cancer. The most important technology for the diagnosis of lung cancer is high-resolution computed tomography. For early stage lung cancer or “ground-glass” nodules, a series of very clear images of the tumor can be obtained, thanks to the tiny intervals between scan slices (1 mm or even lower up to 0.5 mm), which are much thinner than those of normal computed tomography (usually 5 mm). This type of CT gives surgeons the ability to observe slight changes in the nodules over time. Another advantage of high-resolution computed tomography is its ability to reconstruct a three-dimensional image of the target lung, which is crucial for complicated segmentectomy. Other technologies have specific advantages for different types of evaluations. Contrast CT is recommended for most central lung cancers, cancers with enlarged mediastinal lymph nodes, and three-dimensional reconstructions. Positron emission tomography–computed tomography (PET–CT) is being applied with rapidly increasing frequency. As outlined here, there are many methods of diagnosing and staging lung cancer that can be customized to the patient’s health and financial needs. PET–CT is valuable not only for the evaluation of the whole body, and especially for possible distal metastasis, but also for the discovery of some lesions that are difficult to diagnose with CT, because it reveals the active glucose metabolism (standard uptake value) of the lesions. In addition, bone emission CT is often performed to evaluate bone metastatic status for people with financial constraints. Ultrasonography is generally used to detect supraclavicular lymph nodes. Chest radiograph is not usually applied now because it can only reveal large tumors and is not helpful for operation. Magnetic resonance imaging is rarely used except in some special tumors invading the chest wall and mediastinum. After diagnostic imaging, preoperative pathology is important for subsequent treatment plans. Bronchoscopy is of good value for taking biopsy or brush cytology specimens in central lung cancers, through which more than 95% of lesions can be pathologically confirmed.13Chinese guidelines for diagnosis and treatment of primary lung cancer 2018 (English version).Chin J Cancer Res. 2019; 31: 1-28Crossref PubMed Google Scholar CT-guided percutaneous tumor puncture is suitable for peripheral lesions or for people who cannot tolerate bronchoscopy. There are three main ways for nodal staging, which are the following: Endobronchial ultrasound-guided transbronchial needle aspiration is very helpful in the diagnosis of N2 or N3 disease and for the judgment of surgical or systemic therapy–based multimodal treatments. Ultrasound-guided lymph node aspiration is performed for suspicious supraclavicular or cervical node metastasis. Mediastinoscopy, a classic approach for node staging, is now mostly performed in a minimally invasive way (video-assisted mediastinoscopic lymphadenectomy). Some regional medical centers in Guangdong do it very well, whereas most other hospitals tend to treat patients directly by video-assisted thoracoscopic surgery (VATS). The basic examination for lung cancer diagnosis is a chest CT scan. If ground-glass nodules or subsolid nodules are detected and there is suspicion of malignancy, patients should be referred for follow-up procedures. At least one-time follow-up of 3 months is recommended if the surgeon thinks the nodule is “highly suspected for malignancy.” If a peripheral lesion is big enough (>1 cm) and properly located for puncture, CT-guided percutaneous biopsy is recommended. After all evaluation, patients eligible and able to tolerate surgery should be introduced to surgery-based multimodal treatment (Fig. 4). It should be noted that there is no universal treatment plan for all patients suspected of lung cancer; however, imaging, pathology, and follow-up are all very important. All clinical staging in the People’s Republic of China is based on the latest TNM staging system of the Union for International Cancer Control, which is currently in its eighth edition. There is little controversy that surgery is the key player in the treatment of stages I to II lung cancer for eligible patients. Although lobectomy is the standard management in many cases, sublobular resections have been found to have remarkable potential in selected patients with stage I for similar overall survival (OS) and more preserved pulmonary function. Anatomical partial lobectomy is a recently developed surgical technique, which is defined as lesion-centered resection of anatomical sublobular parts, such as segmentectomy, combined segmentectomy, and segmentectomy plus adjacent subsegmentectomy.14Gao S. Qiu B. Li F. et al.[Comparison of thoracoscopic anatomical partial-lobectomy and thoracoscopic lobectomy on the patients with pT1aN0M0 peripheral non-small cell lung cancer].Zhonghua Wai Ke Za Zhi. 2015; 53: 727-730PubMed Google Scholar For resectable stage IIIA cases, the timing of surgery differs because either neoadjuvant or adjuvant systemic therapy can elevate the 5-year survival rate by 5%.15Zhao Y. Wang W. Liang H. et al.The optimal treatment for stage IIIA-N2 non-small cell lung cancer: a network meta-analysis.Ann Thorac Surg. 2019; 107: 1866-1875Abstract Full Text Full Text PDF PubMed Scopus (33) Google Scholar Nodal status, age, and performance status (PS) are important factors that affect survival benefit. Every case is discussed by a multidisciplinary team consisting of surgeons, medical oncologists, and radiation oncologists. Some surgeons prefer to remove the tumor and the affected lymph nodes first if possible. The common interval between systemic therapy and surgery is 4 to 6 weeks and 2 weeks longer if radiotherapy is included in the systemic therapy. In recent years, new therapeutic combinations of surgery with tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors have been attracting wide attention and have been found to have encouraging results in (neo)adjuvant applications.16Gao S. Li N. Gao S. et al.Neoadjuvant PD-1 inhibitor (Sintilimab) in NSCLC.J Thorac Oncol. 2020; 15: 816-826Abstract Full Text Full Text PDF PubMed Scopus (175) Google Scholar,17Zhong W.Z. Wang Q. Mao W.M. et al.Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study.Lancet Oncol. 2018; 19: 139-148Abstract Full Text Full Text PDF PubMed Scopus (360) Google Scholar Surgery is not routinely used in the management of stage IV cancer, although it can be considered in patients who present with resectable oligometastatic lesions and well-controlled primary tumors. The proportion of surgery of metastatic lesions to total surgery volume is not high (less than 10%) in big hospitals but brings substantial survival benefit for eligible patients with advanced-stage disease. Surgery for lung cancer has been evolving very rapidly in the country in the past two decades. In most provincial or regional medical centers, minimally invasive approaches, such as VATS, are widely applied in routine cases. For example, the percentage of VATS in all thoracic surgeries rose over 30% from 2008 to 2014 in the National Cancer Center18Zang R. Shi J.F. Lerut T.E. et al.Ten-year trends of clinicopathologic features and surgical treatment of lung cancer in China.Ann Thorac Surg. 2020; 109: 389-395Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar and even higher (up to 80%) between 2014 and 2019. Surgical incisions became “fewer and smaller,” whereas resection procedures went up to becoming “more complicated and faster.” More surgeons are challenging uniportal VATS on the basis of three portal techniques and practical improvements of surgical instruments to minimize the surgical damage to patients, both physically and psychologically. In contrast, skillful surgeons are trying to accomplish more complicated surgeries, such as sleeve or double-sleeve resection, by VATS. Robotic-assisted thoracic surgery (RATS) is a newly emerging technique used in various lung cancer cases since 2010, mainly for its improved viewing ability and operation at arbitrary angles and is not as technically challenging as it was originally thought to be. In the People’s Republic of China, most experienced surgeons think that VATS can satisfy major clinical requirements of thoracic surgery whereas RATS only has a role in some difficult reconstruction procedures, such as carinoplasty or artery anastomosis. An obvious obstacle for the popularization of RATS is high expense (up to $4 million for the new-generation Da Vinci Xi machine, which is not covered by the National Medical Care Insurance). Thoracotomy is performed in some complex resections (e.g., Pancoast tumor, bulky tumor with enlarged lymph nodes, or large fibrosarcoma). Nevertheless, the advantages of VATS and RATS are gradually becoming indispensable in some scenarios, such as separation of extensive thorax adhesion and surgical experience sharing, which are critical for improvement of surgical movements. There are 1413 radiotherapy centers in the People’s Republic of China. Three-dimensional conformal radiation therapy and intensity-modulated radiation therapy (IMRT) are available in 86.2% and 67.4% centers, respectively, and most are academic cancer centers or with university affiliation.19Wang L. Lu J.J. Yin W. Lang J. Perspectives on patient access to radiation oncology facilities and services in mainland China.Semin Radiat Oncol. 2017; 27: 164-168Crossref PubMed Scopus (10) Google Scholar Advanced technologies, including four-dimensional CT or PET–CT simulation, IMRT/volumetric-modulated arc therapy, image-guided radiation therapy, and motion management, are widely used for lung cancer across the country, and the IMRT technique has been reported to have a significantly improved locoregional recurrence-free survival and comparable OS than three-dimensional conformal radiation therapy in locally advanced NSCLC, along with reduction of pulmonary toxicity.20Wang J. Zhou Z. Liang J. et al.Intensity-modulated radiation therapy may improve local-regional tumor control for locally advanced non-small cell lung cancer compared with three-dimensional conformal radiation therapy.Oncologist. 2016; 21: 1530-1537Crossref PubMed Scopus (26) Google Scholar In the multidisciplinary treatment of lung cancer, radiotherapy is mainly used for early and middle-stage NSCLC. Stereostatic body radiotherapy is the standard treatment for inoperative patients with early disease. Definitive radiotherapy, combined with chemotherapy, is mainly used for those with locally advanced disease, with the standard dose of 60 Gy. Compared with the European and American countries, less Chinese patients might receive concurrent chemoradiation therapy (CCRT). Nevertheless, the percentage of patients receiving CCRT has not been adequately reported. One possible reason is the susceptibility of the Chinese population to radiation pneumonitis according to the early evidence, which has been validated recently in the PACIFIC (Durvalumab after Chemoradiotherapy in Stage III Non–Small-Cell Lung Cancer) study (57.6% [34 of 59] in the CCRT control arm for Asian patients).21Antonia S.J. Villegas A. Daniel D. et al.Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer.N Engl J Med. 2017; 377: 1919-1929Crossref PubMed Scopus (2509) Google Scholar Different genetic backgrounds between whites and Chinese might be a possible explanation.22Wang L. Bi N. TGF-beta1 gene polymorphisms for anticipating radiation-induced pneumonitis in non-small-cell lung cancer: different ethnic association.J Clin Oncol. 2010; 28: e621-e622Crossref PubMed Scopus (27) Google Scholar Therefore, the recommended dose limits of normal lungs are lower in the People’s Republic of China. The mean dose to the lungs should optimally be 17 Gy; the lung volumes, minus gross tumor volume receiving more than 20 Gy (V20) and 30 Gy (V30), were limited to less than 30% and less than 20%, respectively.23Li Y. Ma J.L. Chen X. Tang F.W. Zhang X.Z. 4DCT and CBCT based PTV margin in stereotactic body radiotherapy (SBRT) of non-small cell lung tumor adhered to chest wall or diaphragm.Radiat Oncol. 2016; 11: 152Crossref PubMed Scopus (17) Google Scholar By these limits, similar incidence of radiation pneumonitis could be gained between Chinese and white populations.24Liang J. Bi N. Wu S. et al.Etoposide and cisplatin versus paclitaxel and carboplatin with concurrent thoracic radiotherapy in unresectable stage III non-small cell lung cancer: a multicenter randomized phase III trial.Ann Oncol. 2017; 28: 777-783Abstract Full Text Full Text PDF PubMed Scopus (125) Google Scholar For patients with completely resected pIIIA-N2 NSCLC, the role of postoperative radiotherapy still remains debated. A phase III multicenter trial (NCT 00880917) from the People’s Republic of China indicated that PORT (An Update of the Phase III Trial Comparing Whole Pelvic to Prostate Only Radiotherapy and Neoadjuvant to Adjuvant Total Androgen Suppression: Updated Analysis of RTOG 94-13, With Emphasis on Unexpected Hormone/Radiation Interactions) failed to achieve improved disease-free survival or OS for patients, though it improved locoregional recurrence-free survival.25Hui Z. Men Y. Hu C. et al.A prospective randomized phase Ⅲ study of precise port for patients with pⅢA–N2 NSCLC after complete resection and adjuvant chemotherapy.J Thorac Oncol. 2019; 14: S238-S239Abstract Full Text Full Text PDF Google Scholar For patients with advanced NSCLC, radiotherapy mainly plays a palliative role to improve their quality of life. For limited-stage SCLC, 60 Gy in 30 daily fractions is often used, which is found to have a similar outcome to the 45-Gy 3-week twice-daily regimen but is more convenient for patients and centers. The use of radiation therapy for lung cancer has been significantly increasing in the People’s Republic of China in the past decades. Nevertheless, there is still a gap between availability and demand of radiation therapy. On the basis of the 2017 survey of the People’s Republic of China Society for Radiation Oncology, less than 50% of patients in need of radiotherapy actually received the treatment. This is mainly owing to insufficient number of both equipment and health care providers per million people. For example, the available facility ratio was 1.49 in 2015. In addition, access to radiation therapy varies across the country.19Wang L. Lu J.J. Yin W. Lang J. Perspectives on patient access to radiation oncology facilities and services in mainland China.Semin Radiat Oncol. 2017; 27: 164-168Crossref PubMed Scopus (10) Google Scholar The government is planning to increase medical linear accelerators to 1500 and proton accelerators to 10 in the next few years. Given that more than one-third of patients with lung cancer are initially diagnosed as having advanced/metastatic disease, systemic therapy is the main treatment strategy, including chemotherapy, targeted therapy, and immunotherapy. The selection of therapeutic strategies is based on the histology and molecular pathology of the tumor and age, PS, and the patient’s preferences.26Wang F.H. Shen L. Li J. et al.The Chinese Society of Clinical Oncology (CSCO): clinical guidelines for the diagnosis and treatment of gastric cancer.Cancer Commun. 2019; 39: 10Crossref PubMed Scopus (267) Google Scholar Multidisciplinary teams are encouraged to participate in the discussion of the treatment decisions. After initial morphologic diagnosis, it is strongly recommended to test for treatment-driven strategies. There are distinct testing strategies between squamous cell carcinoma (SCC) and non-SCC. Molecular testing involving EGFR mutations, rearrangements in ALK or ROS1, and BRAF V600E mutation is recommended for non-SCC, especially for adenocarcinoma; for SCC, however, it is only recommended for never-smokers, patients with mixed adenosquamous components, or those with diagnosis based on small biopsies. Although single-gene testing is by far the most common technology used in clinical practice, next-generation sequencing–based multigene testing has become increasingly popular. EGFR mutations represent the most frequent aberrations in lung adenocarcinoma, with a prevalence of around 50% in Chi