Chinese Medical Association Lung Cancer Clinical Diagnosis and Treatment Guidelines (2021 Edition)

Citation format: Oncology Branch of Chinese Medical Association, Journal of Chinese Medical Association.
Guidelines for Clinical Diagnosis and Treatment of Lung Cancer of Chinese Medical Association (2021 Edition)[J].
Chinese Journal of Oncology, 2021, 43(6):591-621.
DOI:10.
3760/ cma.
j.
cn112152-20210207-00118.
Corresponding author: Han Baohui, Department of Respiratory Medicine, Shanghai Chest Hospital, Shanghai Chest Hospital, Shanghai Chest Hospital, Shanghai Chest Hospital, Shanghai 200030, Email: hanxkyy@aliyun.
com [Abstract] The incidence and mortality of lung cancer in China are both ranked first among malignant tumors
.

In order to further standardize China's lung cancer prevention and treatment measures, improve the level of diagnosis and treatment of lung cancer, improve the prognosis of patients, and provide clinical medical staff at all levels with professional evidence-based medical advice, the Chinese Medical Association organizes the Department of Respiratory Medicine, Oncology, Thoracic Surgery, Radiotherapy, and Imaging Experts in the Department of Medicine and Pathology, combined with the recommendations of international guidelines and the current status of clinical practice in China, integrated the latest evidence-based medical evidence in lung cancer pathology, genetic testing, immunological molecular marker detection and treatment methods in recent years, and formulated the Chinese Medicine after the consensus meeting.
The guidelines for clinical diagnosis and treatment of lung cancer (2021 edition) are designed to provide clinicians at all levels, imaging, laboratory, rehabilitation and other professionals with recommendations for lung cancer screening, diagnosis, pathology, treatment and follow-up
.

[Subject words] Lung tumors; diagnosis; treatment; guidelines DOI: 10.
3760/ cma.
j.
cn112152-20210207-00118.
Primary bronchial lung cancer is referred to as lung cancer, which is a malignant tumor with high morbidity and mortality in China and the world One
.

In recent years, the incidence and mortality of lung cancer have shown an obvious upward trend.
According to the statistics of the National Cancer Center of China, the incidence and mortality of lung cancer in China ranked first among malignant tumors in 2015, with about 787,000 new cases and 631,000 deaths.
Males are higher than females, and cities are higher than rural areas.
There are regional differences in morbidity and mortality, with the northeast being the highest, followed by the central, southern, northern, and eastern regions, and the northwestern region being the lowest
.

Most early-stage lung cancer has no obvious symptoms, and most patients with symptoms are already in the advanced stage when they see a doctor.
The overall 5-year survival rate of advanced-stage lung cancer patients is not high
.

In order to further standardize the prevention and treatment of lung cancer in China, improve the diagnosis and treatment of lung cancer, improve the prognosis of patients, and provide clinicians at all levels with professional evidence-based medical advice, the Chinese Medical Association organizes the Department of Respiratory Medicine, Oncology, Thoracic Surgery, Radiotherapy, Imaging and Diseases Scientific experts, combined with international guidelines and China’s national conditions, integrated new advances in lung cancer pathology, genetic testing, immune molecular marker testing and treatment methods in recent years, and formulated the Chinese Medical Association’s Lung Cancer Clinical Diagnosis and Treatment Guidelines (2021 edition), aiming to provide Clinicians at all levels provide evidence-based medicine evidence and guiding opinions in lung cancer screening, diagnosis, pathology, treatment and follow-up
.

This guide makes classification recommendations based on the level of evidence-based medicine (Table 1)
.

1.
Screening for lung cancer For many years, domestic and foreign has been committed to the early diagnosis and treatment of lung cancer through screening, and ultimately reduce lung cancer-related mortality
.

In 2011, the results of a randomized controlled study of the National Lung Cancer Screening Trial in the United States showed that compared with X-ray photography, the use of low-dose spiral CT (low dose computed tomography, LDCT) to screen high-risk lung cancer patients can reduce lung cancer mortality by 20%
.

The lung cancer screening guidelines of many authoritative medical organizations in Europe and the United States all recommend the use of LDCT for lung cancer screening in high-risk groups
.

In recent years, more and more medical institutions in China have carried out or plan to carry out LDCT lung cancer screening, but there are large differences in the domestic understanding of LDCT lung cancer screening and the level of diagnosis and treatment, and clinical practice is not standardized
.

At present, domestic medical institutions mostly carry out LDCT lung cancer screening work based on the more mature foreign programs.
However, compared with Western countries, the risk factors for lung cancer in China are more complicated.
In addition to smoking, there are comprehensive factors such as second-hand smoke and environmental fumes.
Under the influence of, the proportion of female non-smokers in China with lung cancer is much higher than that in Western populations.
Therefore, the specific practice of lung cancer screening must take into account the differences between the East and the West
.

Based on China's lung cancer screening practice and previous domestic and foreign screening guidelines, this guide has formulated the following reference opinions
.

(1) Selection of the screening population for lung cancer risk factors (2A recommendation evidence) 1.
This guideline recommends lung cancer screening in the population of 45 to 75 years old
.

National cancer statistics in 2015 showed that the age-specific incidence and mortality of lung cancer increased significantly after the age of 45.
Therefore, the recommended starting age for lung cancer screening is 45
.

After 75 years of age, the age-specific morbidity and mortality of lung cancer have declined.
Taking into account the life expectancy, comorbidities, surgical tolerance and screening costs of people over 75 years old, lung cancer screening for people over 75 years old The benefit may be small, therefore, the recommended termination age for lung cancer screening is 75 years
.

Lung cancer screening is not recommended for individuals who cannot tolerate possible lung cancer resection surgery or suffer from severe diseases with a short life expectancy
.

Age group (2A recommendation evidence) 2.
The benefit of lung cancer screening increases with the increase in the risk of lung cancer.
Screening high-risk groups is the consensus of screening guidelines at home and abroad
.

This guideline fully considers lung cancer risk factors other than age in the selection of high-risk groups.
Combined with the characteristics of lung cancer in China, it is recommended that people with one of the following risk factors should be screened for lung cancer based on the age group
.

(1) Smoking: Smoking can significantly increase the risk of lung cancer
.

Studies have shown that the risk of lung cancer incidence and death among smokers is higher than that of non-smokers, and the risk of lung cancer incidence and death among smokers in the past is also significantly increased.
At the same time, the smoking dose and the risk of lung cancer are linearly correlated
.

The younger the initial smoking age, the greater the daily smoking, and the longer the duration, the greater the relative risk of lung cancer
.

It is recommended that people who have smoked more than 20 pack years be screened for lung cancer
.

Smoking is more closely related to squamous cell carcinoma and small cell lung cancer (SCLC).
Squamous cell carcinoma and SCLC often exhibit central growth.
Therefore, people who smoke heavily can be screened by fluorescence bronchoscopy.

.

It is recommended to carry out smoking cessation publicity and education in lung cancer screening
.

(2) History of second-hand smoke or environmental fume inhalation: The incidence of lung cancer among non-smokers in Asian population is significantly higher than that of European and American populations, which may be related to second-hand smoke exposure and environmental fume exposure in kitchens and other places
.

Meta analysis shows that secondhand smoke exposure significantly increases the risk of lung cancer
.

Kitchen oil fume produced by cooking methods such as frying can cause DNA damage or cancer, and is one of the important risk factors for lung cancer among Chinese non-smokers
.

(3) Occupational carcinogen exposure history: Long-term exposure to high carcinogens such as radon, arsenic, beryllium, chromium, cadmium and their compounds are more likely to develop lung cancer
.

Asbestos exposure can significantly increase the risk of lung cancer
.

In addition, silica and soot are also clear carcinogens of lung cancer
.

(4) Personal tumor history: People suffering from other malignant tumors in the past may carry abnormal gene mutations, which can increase the risk of lung cancer
.

Research on genetic screening for lung cancer is still ongoing
.

(5) Family history of lung cancer in immediate relatives: Individuals whose first-degree relatives are diagnosed with lung cancer have a significantly higher risk of developing lung cancer
.

People with a family history of lung cancer may have genetic susceptibility sites for lung cancer
.

(6) History of chronic lung disease: The incidence of lung cancer in patients with chronic obstructive pulmonary disease, tuberculosis, and pulmonary fibrosis is higher than that of healthy people
.

Chronic inflammation of bronchopulmonary tissue and its squamous epithelial metaplasia or hyperplasia during the healing process may develop into lung cancer
.

(2) Screening technology LDCT (Class 1 recommendation evidence) 1.
Currently, the lung cancer screening guidelines released worldwide recommend the use of LDCT for lung cancer screening
.

Many studies at home and abroad have shown that compared with chest X-ray, LDCT can significantly increase the detection rate of lung cancer and reduce lung cancer-related mortality, with higher sensitivity and specificity
.

This guide recommends the use of LDCT for lung cancer screening
.

Other techniques (3 types of recommended evidence) 2.
For suspicious airway disease, it is recommended to use fiberoptic bronchoscopy for further examination
.

The method of lung cancer screening through peripheral blood circulating tumor cells, tumor free DNA, microRNA and other methods is still being explored
.

The combined application of auxiliary testing methods and LDCT screening may reduce excessive false positive results
.

(3) Screening frequency (Type 2A recommendation evidence) It is recommended that the interval of screening is 1 year, and the screening mode with an interval of> 2 years is not recommended
.

If the annual screening results are normal, it is recommended to continue the screening every 1 to 2 years
.

(4) Screening organization personnel (Type 1 recommendation evidence) The key to implementing lung cancer screening is that there must be a team of multidisciplinary experts who work together.
It is recommended that medical institutions for lung cancer screening should establish imaging, respiratory medicine, thoracic surgery, and oncology departments.
A multidisciplinary collaborative team including others
.

(V) Screening CT quality control and reading requirements (2B recommended evidence) 1.
CT quality control: It is recommended that medical institutions with conditions use 16-row and above multi-slice spiral CT for LDCT lung cancer screening
.

The subject was in a supine position, and the scan was completed with one breath-hold at the end of inhalation.
The scan range was from the lung tip to the costophrenic angle
.

It is recommended that the scan matrix setting is not less than 512×512, the tube voltage is 100～120 kVp, and the tube current is less than or equal to 40 mAs
.

After scanning, the original data adopts lung algorithm or standard algorithm for thin layer reconstruction.
It is recommended that the thickness of the reconstructed layer is 0.
625～1.
25 mm, and there is 20%～30% overlap between the layers
.

For the detection of lung nodules, it is recommended that the thin-layer image be reconstructed in three dimensions, and the maximum density projection reconstruction is used, which is helpful for the observation of the nodule morphology
.

2.
Reading requirements: It is recommended to use DICOM format for reading in workstations or PACS, using lung window (window width 1 500～1 600 HU, window level -650～-600 HU) and mediastinal window (window width 350～380 HU) , Window level 25～40 HU) read the film separately
.

It is recommended to use multi-planar reorganization and maximum density projection to read the film to display the morphological characteristics of lung nodules in multiple directions
.

It is recommended to use image comparison rather than report when comparing with previous examinations, which is very important for assessing the specific size, shape and density changes of nodules
.

(6) Screening results management Recommendations for the management of baseline screening results (Class 2A recommendation evidence) 1.
(1) Those who have airway disease found in the screening suggest clinical intervention and perform fiberoptic bronchoscopy.
If the fiberoptic bronchoscopy result is negative, It is recommended to enter the next year's LDCT screening; if it is positive, it is recommended to decide whether to conduct clinical treatment or enter the next year's high resolution computed tomography (HRCT) screening after a multidisciplinary consultation
.

(2) No non-calcified nodules in the lung were detected (negative result), or the average diameter of the detected non-solid nodules was less than 8 mm, or the average diameter of the solid components of solid nodules/partial solid nodules <5 mm, it is recommended to enter the next year's LDCT screening
.

(3) The average diameter of the detected non-solid nodules is ≥8 mm, or the average diameter of the solid components of solid nodules/partial solid nodules is ≥5 mm.
If malignant nodules cannot be ruled out, anti-inflammatory treatment or Review HRCT after follow-up
.

If the nodule is completely absorbed, it is recommended to enter the next year's LDCT screening; if the nodule is partially absorbed, recheck the HRCT after 3 months; if it continues to be absorbed or completely absorbed, it is recommended to enter the next year's LDCT screening; if there is no change or increase, it is recommended After multidisciplinary consultation, it is decided whether to conduct clinical treatment
.

If there is no absorption of nodules after anti-inflammatory treatment or follow-up HRCT, it is recommended to decide whether to conduct clinical treatment or enter the next year's HRCT screening after multidisciplinary consultation
.

For highly suspected malignant nodules, clinical diagnosis and treatment are recommended
.

Recommendations for management of annual screening results (Class 2A recommendation evidence) 2.
(1) New airway disease found in screening is recommended for clinical intervention and fiberoptic bronchoscopy.
If fiberoptic bronchoscopy results are negative, it is recommended to enter the next year's LDCT screening If it is positive, it is recommended to decide whether to conduct clinical treatment or enter the next annual HRCT screening after a multidisciplinary consultation
.

(2) If the screening result is negative or there is no change in the nodules detected in the previous year, it is recommended to enter the next year's LDCT screening
.

(3) If enlarged nodules or solid components were detected in the previous year, clinical diagnosis and treatment is recommended
.

(4) If a new non-calcified nodule is detected, if the average diameter of the nodule is less than 5 mm, it is recommended to review the HRCT after 6 months.
If the nodule is not enlarged, it is recommended to enter the next annual screening; if it is enlarged, it is recommended to multi-disciplinary After the consultation, it is decided whether to conduct clinical treatment or enter the next year's screening
.

If the average diameter of the nodule is ≥5 mm, anti-inflammatory treatment or follow-up is recommended, and the HRCT should be reviewed after 3 months.
If the nodule is completely absorbed, it is recommended to enter the next year's screening; if the nodule is partially absorbed, the HRCT should be reviewed after 6 months, such as If it continues to be absorbed or completely absorbed, it is recommended to enter the next year's screening; if there is no change or increase, it is recommended to decide whether to conduct clinical treatment after a multidisciplinary consultation
.

If anti-inflammatory treatment or re-examination of chest HRCT after 3 months of follow-up, it is found that the nodule has no absorption, it is recommended to decide whether to conduct clinical treatment after multidisciplinary consultation
.

False positive and overdiagnosis (2A recommendation evidence) 3.
Although lung cancer screening can reduce lung cancer mortality, there are still some potential harms in screening, such as false positive results, which can lead to unnecessary invasive examinations and overdiagnosis
.

Therefore, it is recommended that screening agencies use a complete description and introduction to enable the screening population to fully understand the benefits, limitations and potential harms of lung cancer screening
.

Lung cancer autoantibody-related tests can also be used as a reference index for risk stratification of lung nodules, providing information about active or inert biological characteristics
.

The etiology of pulmonary nodules is complicated.
It is recommended to comprehensively evaluate the imaging, biological and clinical characteristics of pulmonary nodules
.

The population selection for lung cancer screening is shown in Figure 1, the baseline screening lung nodule management process is shown in Figure 2, and the annual screening lung nodule management process is shown in Figure 3
.

2.
Diagnosis of lung cancer The diagnosis process of lung cancer is shown in Figure 4
.

(1) Clinical manifestations of lung cancer Central type lung cancer can exhibit corresponding intrathoracic symptoms, including cough, sputum, hemoptysis, wheezing, chest tightness, shortness of breath, chest pain, hoarseness, dysphagia, superior vena cava syndrome, and diaphragmatic paralysis , pleural and pericardial effusions, Pancoast syndrome
.

Distant metastasis can have different local and systemic symptoms depending on the location of the metastasis
.

Peripheral lung cancer often has no respiratory symptoms in the early stage.
As the disease progresses, corresponding respiratory symptoms or metastasis-related symptoms may appear
.

A small number of patients with lung cancer may have some rare symptoms and signs that are not caused by direct invasion or metastasis of the tumor, also known as paraneoplastic syndrome, which can occur before or after the diagnosis of lung cancer, and can also occur at the same time, often manifesting as organs other than the chest.
symptoms such as hypercalcemia, antidiuretic hormone secretion syndrome, ectopic Cushing's syndrome, neuromuscular function abnormalities, abnormal blood system
.

(2) Auxiliary imaging examination of lung cancer During the diagnosis and treatment of lung cancer, it is recommended that one or more imaging examination methods be selected reasonably and effectively according to different examination purposes
.

The auxiliary imaging examination methods for lung cancer mainly include X-ray photography, CT, magnetic resonance imaging (MRI), positron emission tomography computed tomography (PET CT), ultrasound, radionuclide imaging, etc.
Method
.

Imaging examinations are mainly used for lung cancer diagnosis, staging, efficacy monitoring, re-staging and prognostic evaluation
.

1.
Chest X-ray photography: Chest X-ray photography is the basic examination method of the chest, which usually includes frontal and lateral chest radiographs
.

When abnormal chest X-ray images are found, further imaging examination methods should be selected in a targeted manner
.

Although the spatial resolution of X-ray photography is relatively high, the density resolution is lower than that of CT.
Currently, it is mostly used for routine hospital admission or post-operative review
.

2.
Chest CT: Chest CT can effectively detect early peripheral lung cancer and clarify the location and extent of the lesion.
It is currently the main imaging method for diagnosis, staging, efficacy evaluation and follow-up
.

Advantages of CT examination: (1) High density resolution, which can detect tiny nodules with a diameter of only 2 mm or more and hidden X-ray overlapping areas (such as posterior heart shadow, upper diaphragm, paramediastinum, clavicle and rib projection area) Bottom) lesions; (2) Volume acquisition, through CT, especially HRCT thin-layer reconstruction and three-dimensional reconstruction, comprehensive analysis and discovery of imaging features that distinguish benign and malignant tumors can also be helpful for accurate follow-up; (3) comparison The agent enhancement check provides functional information and comprehensive evaluation
.

The use of contrast agent can not only improve the qualitative ability of the lesion and display the blood supply of the solid lesion, but also help to detect and distinguish the blood vessels, hilar and mediastinum with or without enlarged lymph nodes, so as to make more accurate clinical staging and curative effects of lung cancer.
It is of great significance to evaluate and judge the possibility of surgical resection
.

3.
MRI examination: MRI is generally not used for routine examination of lung cancer, but it can be selectively used in the following cases to determine the chest wall or mediastinum invasion, showing the relationship between superior sulcus tumors and brachial plexus nerves and blood vessels.
Diameter> 8 mm is difficult to confirm Differential diagnosis of sexual pulmonary nodules
.

MRI examination has important potential value in the accurate curative effect evaluation of lung cancer
.

In addition, it is recommended to use enhanced MRI to determine whether there are brain metastases and local bone metastases
.

4.
PETCT examination: PETCT is one of the best methods for diagnosis of lung cancer, staging and restaging, radiotherapy target area delineation (especially when combined with atelectasis or contraindications to intravenous CT imaging), efficacy and prognosis evaluation
.

PET-CT has relatively poor sensitivity for the diagnosis of brain and meningeal metastases.
If necessary, it needs to be combined with brain-enhanced MRI to improve the detection rate
.

It is recommended to perform PET-CT examinations for those with conditions
.

5.
Ultrasonography: Ultrasonography is generally not used for routine examination of lung cancer.
It is often used to check the abdominal organs and superficial lymph nodes for metastasis.
Ultrasound-guided needle biopsy of superficial lymph nodes, intrapulmonary lesions adjacent to the chest wall, or chest wall lesions It can also be used to check for pleural metastasis, pleural effusion and pericardial effusion, and can be used for ultrasound positioning to extract pleural effusion
.

6.
Bone scan: Bone scan is a routine examination for judging bone metastases from lung cancer, and it is the first choice for screening bone metastases
.

When bone scans find suspicious bone metastases, MRI can be used for further confirmation
.

In staging diagnosis of lung cancer patients, PET-CT and brain-enhanced MRI can be performed if conditions permit, and chest-enhanced CT, abdomen-enhanced CT or ultrasound (examination scope must include supraclavicular lymph nodes), head Enhanced CT or MRI, whole body bone scan
.

The advantages and disadvantages of different imaging methods are shown in Table 2
.

(3) When obtaining lung cancer cytology or histological examination techniques to obtain pathological specimens, if conditions permit, in addition to cytology, it is recommended to obtain tissue specimens as much as possible.
In addition to diagnosis, genetic testing can also be performed
.

1.
Sputum cytology examination: Sputum cytology examination is one of the most simple and convenient non-invasive diagnostic methods for the diagnosis of central lung cancer, but there are certain false positives and false negatives, and typing is more difficult
.

2.
Thoracentesis: Thoracentesis can obtain pleural effusion for cytological examination, in order to clarify the pathology and stage lung cancer
.

Paraffin embedding, slicing and staining can be performed on the cell block deposited by centrifugation of pleural effusion to improve the positive diagnosis rate of pathology
.

The metastatic serous effusion located in other parts can also be punctured to obtain pathological evidence
.

3.
Biopsy of superficial lymph nodes and subcutaneous metastatic lesions: For patients with lung cancer suspected of occupying space, if superficial subcutaneous lesions or superficial lymph node enlargement are found, a biopsy can be performed to obtain a pathological diagnosis
.

4.
Transthoracic lung puncture: Transthoracic lung puncture under the guidance of CT or ultrasound is one of the preferred methods for the diagnosis of peripheral lung cancer
.

5.
Bronchoscopy: Bronchoscopy is one of the main diagnostic tools for lung cancer
.

Bronchoscopy can enter the bronchus of grade 4 to 5 to help visually observe about 1/3 of the bronchial mucosa, and obtain histological or cytological materials through biopsy, brushing and lavage.
The combined application of biopsy, brushing and lavage can be used Improve the detection rate
.

The deficiencies of conventional bronchoscopy mainly include: (1) The scope of the examination is limited, and it is impossible to observe the peripheral 2/3 of the respiratory tract with naked eyes; (2) It is impossible to observe the extraluminal lesions and lymph nodes directly; (3) For respiratory tract mucosal epithelial abnormalities The diagnosis rate of hyperplasia and carcinoma in situ is not high
.

Fluorescence bronchoscopy is a bronchoscopy technology developed using the principle that the autofluorescence of tumor tissue is different from that of normal tissue.
Combined with conventional bronchoscopy, it can significantly improve the diagnosis of intraepithelial neoplasia and invasive lung cancer
.

For lesions that cannot be observed by conventional bronchoscopy, according to the location of the lesion and the specific conditions of different units, the bronchoscope can be guided through X-ray fluoroscopy, radial ultrasound probe, magnetic navigation and other technologies to obtain pathological results
.

6.
Conventional transbronchial needle aspiration (TBNA) and endobronchial ultrasound guided transbronchial needle aspiration (EBUSTBNA): traditional TBNA is based on CT positioning of chest lesions.
The requirements of the surgeon are high, and it is not a routinely recommended inspection method.
Hospitals with conditions can carry out
.

EBUS TBNA can perform real-time puncture of intrathoracic lesions, mediastinum, and hilar lymph node metastases under ultrasound guidance.
It is safer and more reliable.
It is recommended that qualified hospitals actively carry out the puncture
.

When physicians suspect mediastinal and hilar lymph node metastasis and other staging methods are difficult to determine, it is recommended to use invasive methods such as EBUS TBNA to determine the status of mediastinal lymph nodes
.

7.
Mediastinoscopy: Mediastinoscopy has a large number of samples and is an effective method to identify benign and malignant diseases with mediastinal lymphadenopathy.
It is also one of the methods to assess the staging of lung cancer, but the operation trauma and risk are relatively large
.

8.
Thoracoscopy: Internal thoracoscopy can be used for the diagnosis of unexplained pleural effusion and pleural diseases
.

Surgical thoracoscopy can effectively obtain diseased lung tissues.
For lung cancers that cannot be obtained pathological specimens through bronchoscopy and transthoracic lung puncture, especially small lung nodules, the lesions can be cleared by thoracoscopic resection.
Diagnosis
.

For patients who are considered to have advanced lung cancer, if other examination methods cannot clarify the pathology, thoracoscopy can also be used to perform lung lesions and pleural biopsy to provide a reliable basis for formulating a comprehensive treatment plan
.

(4) Serological laboratory examination of lung cancer Serological examination is helpful for the auxiliary diagnosis, efficacy judgment and follow-up monitoring of lung cancer
.

Currently, the commonly used markers for primary lung cancer are carcino embryonic antigen (CEA), neuron specific enolase (NSE), and cytokeratin 19 fragment antigen 211 (CYFRA211).
, gastrin releasing peptide precursor (progastrinreleasing peptide, proGRP), squamous cell carcinoma antigen (squamous cell carcinoma antigen, SCCA) and the like
.

Combined detection of tumor markers can improve its sensitivity and specificity in clinical applications
.

The diagnosis of lung cancer usually requires a combination of imaging and pathology
.

Although the sensitivity and specificity of lung cancer serum tumor markers are not high, the increase can sometimes be earlier than the appearance of clinical symptoms
.

Therefore, the detection of lung cancer-related tumor markers is helpful in assisting diagnosis and early differential diagnosis and predicting the pathological type of lung cancer
.

The level of tumor markers is related to tumor burden and stage.
It is recommended to perform tumor marker detection to understand the baseline level before the first diagnosis and start of treatment.
Monitoring the dynamic changes of marker levels after treatment can be used in the monitoring of tumor efficacy and prognosis.
Play a role
.

In the long-term monitoring of cancer patients, changing the detection methods of tumor markers can lead to differences in results.
Therefore, the results of tumor markers of different detection methods should not be directly compared
.

Pay attention to exclude the influence of diet, drugs, comorbid diseases and other factors on the test results
.

For patients with no clear new or progressive lesions on imaging examination, but only tumor markers continue to rise, it is recommended to look for the cause, be alert to the possibility of disease recurrence or progression, and close follow-up is required
.

1.
SCLC: NSE and ProGRP are the first choices for diagnosing SCLC
.

NSE is secreted by central or peripheral neurons and neuroectodermal tumors.
When the histological results cannot be diagnosed, NSE can assist in the diagnosis of SCLC; hemolysis will significantly affect the NSE test results.
It should be separated from red blood cells within 60 minutes to prevent False increase
.

As a single marker, ProGRP is more specific than other markers in the diagnosis of SCLC, and it is positively correlated with SCLC staging, which helps to distinguish SCLC from benign lung diseases
.

Elevated ProGRP concentration can also occur in patients with renal insufficiency, and its level is related to serum creatinine.
Therefore, when the ProGRP level rises and is not consistent with the patient's clinical symptoms, the patient's serum creatinine level should be evaluated first
.

2.
Nonsmall cell lung cancer (NSCLC): In patients' serum, elevated levels of CEA, SCCA, and CYFRA21 1 help to diagnose NSCLC
.

CEA is most significantly elevated in lung adenocarcinoma and large cell lung cancer, and the sensitivity is higher
.

However, it should be noted that increased CEA can also be seen in gastrointestinal tumors and pulmonary interstitial fibrosis
.

Combined detection of CYFRA211 and CEA can improve the sensitivity and specificity of lung adenocarcinoma diagnosis
.

The CEA level of long-term smokers may be slightly higher than that of healthy people
.

CYFRA211 is also one of the sensitive indicators of NSCLC.
It should be noted that skin and saliva contamination and CYFRA211 may be falsely elevated in patients with renal failure
.

SCCA has high specificity for squamous epithelial tumors such as lung squamous cell carcinoma, which can assist histological diagnosis
.

However, a single marker cannot distinguish SCLC from NSCLC
.

About 10% of NSCLC have an immune response to at least one of the neuroendocrine markers
.

If combined detection of NSE, ProGRP, CYFRA211, CEA and SCCA and other indicators, the identification accuracy can be improved
.

3.
Pathological evaluation of lung cancer (1) Pathological subtypes Pathological evaluation 1.
The purpose of pathological evaluation is to clarify the nature of the lesion and provide relevant information for clinical pathological staging, as well as the quality control of molecular test specimens
.

The types of specimens for pathological evaluation include biopsy specimens, cytology specimens, surgical resection specimens, and other specimens for molecular testing
.

(1) Biopsy specimens or cytology specimens: ①Accurate diagnosis according to the 2021 World Health Organization (WHO) classification, pathological diagnosis, while keeping enough specimens for molecular biology and immunotherapy related tests as much as possible (Class 1 recommended evidence )
.

②When the patients with disease progression after treatment are biopsy again, under the premise of clarifying the tissue type, perform corresponding molecular pathological testing according to the needs of diagnosis and treatment (2A recommendation evidence)
.

③ Strive to clarify the tissue subtype, and only when the specimen has no obvious differentiation or phenotypic characteristics can be diagnosed non-small cell carcinoma not otherwise specified (NSCC NOS) (2A recommendation evidence)
.

④ For cytology specimens, make cell wax blocks as much as possible at the same time (type 2B recommendation evidence)
.

(2) Surgical specimens: surgical specimens are used to clarify the nature and tissue type of the tumor, tumor stage, molecular pathology detection and prognostic information (including tumor size, surrounding tissue invasion, surgical margins and lymph node metastasis, etc.
) (2A Class recommendation evidence)
.

①The number and location of lymph node metastasis need to be indicated in detail in the report.
The primary tumor infiltrating into adjacent lymph nodes should be diagnosed as lymph node metastasis; ②When pleural invasion is suspected, special staining of elastic fiber should be used to further confirm; ③spread through air spaces, STAS) It is recommended to indicate in the report (2B recommendation evidence); ④The size of the tumor and the distance between the tumor and the surgical margin, surrounding tissues, etc.
should be accurately measured, with a measurement accuracy of mm; ⑤For multiple lung lesions, It is recommended to evaluate the relationship between the lesions according to the methods recommended by the international classification standards
.

Histopathological type 2.
Histological classification adopts the 2021 version of WHO lung tumor histological classification standard
.

(1) Diagnosis principles of tissue specimens (Class 2A recommended evidence) ① Squamous cell carcinoma: Squamous cell carcinoma is an epithelial malignant tumor with keratinization and/or intercellular bridges or expression of squamous cell differentiation markers, including squamous cell carcinoma.
Cell carcinoma and lymphoepithelial carcinoma
.

Squamous cell carcinoma is divided into three subtypes: keratinizing squamous cell carcinoma, non-keratinizing squamous cell carcinoma and basaloid squamous cell carcinoma
.

Lymphoepithelial carcinoma is poorly differentiated squamous cell carcinoma with varying numbers of lymphocytes and plasma cells infiltrated.
It is often positive for Epstein-Barr virus.
It should be distinguished from nasopharyngeal carcinoma
.

Squamous atypical hyperplasia and squamous cell carcinoma in situ are squamous precursor lesions
.

②Adenocarcinoma: Adenocarcinoma includes minimally invasive adenocarcinoma (MIA), invasive non-mucinous adenocarcinoma, invasive mucinous adenocarcinoma, colloidal adenocarcinoma, fetal type adenocarcinoma, and intestinal type adenocarcinoma
.

MIA means that the tumors are mainly adherent components, and the maximum diameter of the infiltrating components is ≤5 mm
.

The size of MIA tumor is ≤30 mm and there is no pleura, bronchus, vascular invasion, tumor necrosis, and STAS
.

Lung invasive non-mucinous adenocarcinoma is evidence of adenoid differentiation in morphology or immunohistochemistry
.

Common subtypes include adherent type, acinar type, papillary type, micropapillary type and solid type, and multiple subtypes are often mixed
.

The pathological diagnosis is listed in descending order of the proportion of each subtype, and the proportion of each subtype is increased by 5%
.

Non-mucinous, purely adherent lung adenocarcinoma with a diameter of more than 30 mm should be diagnosed as adherent invasive non-mucinous adenocarcinoma
.

The grading scheme for early invasive non-mucinous adenocarcinoma was proposed by the Pathology Committee of the International Association for the Study of Lung Cancer
.

According to the predominant histological type and the proportion of high-grade structures in adenocarcinoma, it is divided into 3 grades, grade 1 is well differentiated, grade 2 is moderately differentiated, and grade 3 is poorly differentiated
.

Highly differentiated as adherent-based type without high-grade components, or accompanied by <20% high-grade components; moderately differentiated as acinar or nipple-based type without high-grade components, or accompanied by <20% high-grade components; poorly differentiated For any histological type of adenocarcinoma with ≥20% of high-grade components
.

High-level structures include solid, micropapillary, sieve, and complex gland structures (that is, fused glands or single cells infiltrate in the interstitium that promotes connective tissue proliferation)
.

Adenocarcinoma in situ (AIS) refers to adenocarcinoma with a simple adherent growth pattern.
At present, AIS and lung atypical adenomatous hyperplasia are classified as adenoid precursor lesions
.

③Adenosquamous carcinoma: refers to two components containing adenocarcinoma and squamous cell carcinoma, each component accounts for at least 10% of all tumors
.

④ Neuroendocrine tumors: including neuroendocrine tumors (NETs) and neuroendocrine cancers; among them, NETs include low-grade typical carcinoid (TC), medium-grade atypical carcinoid (AC), neuroendocrine tumors Cancers include SCLC and large cell neuroendocrine carcinoma (LCNEC)
.

Composite SCLC refers to any histological type of SCLC combined with NSCLC, combined with large cells and large cell components accounted for ≥10%, diagnosed as combined SCLC/LCNEC or SCLC/large cell carcinoma, combined with other NSCLC without proportion requirements
.

Compound LCNEC refers to LCNEC with other NSCLC components
.

The indicators of mitosis and necrosis are the main pathological indicators to distinguish the four types of neuroendocrine tumors (2A recommendation evidence)
.

The Ki 67 index is only helpful in identifying high-grade and low-grade neuroendocrine cancers in small biopsy specimens (type 2B recommendation evidence)
.

Neuroendocrine markers NCAM (CD56), chromogranin, and synaptophysin are only used for morphologically suspected neuroendocrine tumors.
TC and AC express at least two neuroendocrine markers, and SCLC and LCNEC express at least one neuroendocrine marker
.

A small part of SCLC can be expressed without any neuroendocrine markers
.

The non-specific carcinoid refers to situations where TC and AC are not easily distinguishable.
It is recommended to label the number of mitosis, presence or absence of necrosis, and Ki67 index
.

Non-specified carcinoids are mainly used in the following situations: some small biopsies or cytology specimens are difficult to distinguish between TC and AC due to limited tissue; lung metastatic carcinoids; some surgical specimens do not provide all sections of tumor tissue
.

⑤Large cell carcinoma: Large cell carcinoma is an undifferentiated non-small cell carcinoma which lacks small cell carcinoma, squamous cell carcinoma, adenocarcinoma, giant cell carcinoma and spindle cell in terms of cell morphology, tissue structure, immunohistochemistry and histochemistry.
The characteristic of cancer and pleomorphic cancer is the diagnosis of exclusion
.

⑥ Sarcomatoid carcinoma: Sarcomatoid carcinoma includes pleomorphic carcinoma, carcinosarcoma and pulmonary blastoma
.

Pleomorphic carcinoma is NSCLC that contains at least 10% spindle or giant cell components
.

Spindle cell carcinoma or giant cell carcinoma contains almost only spindle or giant cell components
.

Carcinosarcoma is an NSCLC with mixed sarcoma components
.

Pulmonary blastoma includes fetal adenocarcinoma and bidirectionally differentiated tumors of primitive mesenchymal components
.

⑦Other epithelial tumors: chest SMARCA4 deletion undifferentiated tumor is a high-grade malignant tumor, mainly involving the chest of adults, showing an undifferentiated or rhabdoid phenotype accompanied by SMARCA4 deletion
.

Cytotoxic chemotherapy is usually ineffective for the tumor
.

NUT carcinoma is a poorly differentiated carcinoma with 15q14 NUTM1 gene rearrangement and expression of nuclear protein in testis (NUT)
.

NUT cancer is very aggressive, and most chemotherapy regimens are ineffective.
Clinical studies on the treatment of NUT cancer with BET small molecule inhibitors targeting BRD4 are ongoing
.

For other rare types, please refer to the 2021 WHO classification
.

⑧ Metastatic tumors: The lung is a common metastatic site of tumors throughout the body, and attention should be paid to exclude metastatic tumors
.

Immunohistochemistry helps to identify tissue sources, such as lung (TTF 1 and Napsin A), breast (GCDFP15, Mammaglobin and GATA3), renal cell carcinoma (PAX8 and RCC), gastrointestinal tract (CDX2 and Villin), prostate (NKX3) .
1 and prostate specific antigen) and mesothelium (WT 1, Calretinin, D240 and GATA3), etc.
(2A recommendation evidence)
.

(2) Principles of cytological specimen diagnosis (Class 2A recommendation evidence) ①Use NSCC NOS as little as possible; ②When paired cytology and biopsy specimens are available, comprehensive diagnosis should be made to achieve consistency; ③Tumor cells or The specimens of suspicious tumor cells should be made as much as possible to make cytological wax blocks; ④The classification of cytological specimens is not recommended to be too detailed, only for adenocarcinoma, squamous cell carcinoma, neuroendocrine carcinoma or NSCC NOS classification
.

(2) Immunohistochemical testing (Class 2A recommendation evidence) 1.
Principle: Use immunohistochemical staining with caution for small biopsy specimens in order to preserve tissues for treatment-related testing
.

2.
Lung cancer with unclear morphology: The use of 1 adenocarcinoma marker TTF 1 and 1 squamous cell carcinoma marker (P40) in biopsy specimens can solve most of the typing problems of NSCLC
.

For surgical specimens: ①Use a set of antibodies to identify adenocarcinoma and squamous cell carcinoma
.

②When neuroendocrine morphology appears, a set of molecular markers are used to confirm neuroendocrine differentiation
.

③For poorly differentiated cancers or malignant tumors, NUT, SMARCA4 (BRG 1) and (or) INI 1, SOX 2 and other immunohistochemical tests can be used to exclude rare histological types such as NUT cancer and SMARCA4 deletion undifferentiated tumors
.

④ Perform EBER in situ hybridization for poorly differentiated carcinoma or non-keratinizing squamous cell carcinoma with obvious lymphocytic infiltration
.

3.
For advanced NSCLC, as important as driver gene testing, the expression of programmed death ligand 1 (PD-L1) should be tested (type 2A recommendation evidence)
.

(3) Molecular pathology detection 1.
Specimen types: In addition to acid-treated specimens, formaldehyde-fixed, paraffin-embedded specimens, cell blocks and cell smears are all suitable for molecular detection
.

All histological and cytological specimens to be tested shall be subject to quality control by pathologists to evaluate tumor type, cell content, necrosis rate, select histological types suitable for molecular testing, and ensure that there are sufficient tumor cells to extract DNA or RNA (recommended for category 1 Evidence)
.

If conditions are available, tumor enrichment operations can be performed (type 2A recommendation evidence)
.

2.
Basic principles: (1) After the routine histological diagnosis of the specimen, try to retain enough tissue for molecular biological testing, and guide the treatment according to molecular typing (type 1 recommendation evidence); after the histological diagnosis of advanced NSCLC, it is necessary to retain enough tissue for molecular biology Scientific testing, guide treatment based on molecular classification (type 2A recommendation evidence)
.

(2) NSCLC containing adenocarcinoma components, regardless of its clinical characteristics (such as smoking history, gender, race or other, etc.
), should be routinely treated with epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase ( Anaplastic lymphoma kinase, ALK), ROS1 (Class 2A recommendation evidence), and RET molecular biology test (Class 2B recommendation evidence).
It is recommended that surgical pathological specimens be tested for EGFR (Class 2A recommendation evidence) for patients after stage IB to III
.

The detection method should select reagents and platform equipment officially approved by the country, or use the officially approved next generation sequencing (NGS) detection reagent platform
.

When the tissue is limited and/or insufficient for molecular biological testing, plasma free DNA can be used to detect EGFR mutations (type 2A recommendation evidence)
.

(3) The recommended genes for NSCLC testing are EGFR, ALK, and ROS1 (Class 1 recommended evidence), and the extended genes are BRAFV600E mutation, MET amplification and MET14 exon skip mutation, human epidermal growth factor receptor 2, KRAS, RET Etc.
(2A type recommendation evidence)
.

NGS can be used to detect all required genes and extended genes at the same time.
It can also be used to test for extended genes after routine detection of EGFR, ALK, and ROS1 genes is negative.
If tissue samples are not available, consider using circulating tumor DNA (circulating tumor DNA).
DNA, ctDNA) for testing (type 2B recommendation evidence)
.

(4) For patients with EGFR tyrosine kinase inhibitor (TKI) resistance, a second biopsy is recommended for secondary drug-resistant EGFR T790M testing; for patients who cannot obtain tissues, ctDNA can be used for EGFR T790M testing (Type 2A recommendation evidence)
.

When ctDNA is negative, the patient should still be advised to undergo tissue testing to confirm the EGFR T790M mutation status
.

Both primary tumors and metastatic lesions are suitable for targeted driver gene detection (type 1 recommendation evidence)
.

Screening methods for tumor immunotherapy patients: (1) Immunohistochemical detection of PD-L1 expression in NSCLC can find patients who may be effective for immunotherapy
.

The immunohistochemical detection of PD-L1 has a variety of antibody clone numbers, corresponding to different therapeutic drugs.
The judgment criteria should refer to the instructions of each kit.
The pathologist responsible for the diagnosis must pass the corresponding interpretation training (2B recommendation evidence)
.

(2) Tumor mutation burden (tumor mutation burden, TMB) may be another marker for predicting the effect of immunotherapy
.

At present, there is no uniform standard (three types of recommended evidence) for the selection of TMB detection methods and thresholds
.

Fourth, the principles of staging treatment of lung cancer 1.
Surgical radical resection is the recommended and preferred local treatment for stage I and II NSCLC
.

2.
Stage III NSCLC is a type of tumor with obvious heterogeneity
.

According to the 8th edition of the International Society for Lung Cancer Research, stage III NSCLC is divided into stage IIIA, IIIB, and IIIC
.

Stage ⅢC and most of stage ⅢB are classified as unresectable stage Ⅲ NSCLC
.

The main treatment mode is radical concurrent radiotherapy and chemotherapy (Type 1 recommendation evidence)
.

The treatment modes of stage ⅢA and a small part of stage ⅢB NSCLC are divided into unresectable and resectable
.

For unresectable patients, the treatment is based on radical concurrent radiotherapy and chemotherapy; for resectable patients, the treatment mode is comprehensive treatment based on surgery (type 2A recommendation evidence)
.

3.
Systemic treatment for patients with stage IV NSCLC is recommended based on the identification of the patient’s NSCLC pathological type (squamous or non-squamous) and driver gene mutation status and the Eastern United States Oncology Group functional status score (Table 3), and the selection of a systemic body suitable for the patient Treatment plan
.

5.
Treatment of lung cancer (1) Comprehensive treatment for patients with stage I and II NSCLC (Figure 5) The importance of surgical treatment 1.
(1) Surgeons should actively participate in the judgment and functional evaluation of the clinical staging and resection possibility of the patient.
According to the degree of tumor progression and the functional status of the patient, the possibility of surgery and the method of surgery are determined
.

(2) When the physical function of high-risk patients may not tolerate radical surgical resection, a multidisciplinary team including surgeons should first discuss other local treatment methods, such as stereotactic body radiotherapy (SBRT) , frozen and radiofrequency ablation and so on
.

Surgical method 2.
(1) Principle: Complete and thorough resection is the key to ensuring radical surgery, accuracy of staging, strengthening local control and long-term survival
.

(2) Surgical method: Anatomical lung resection is still the standard surgical method (Type 1 recommendation evidence)
.

①The results of the 1995 LCSG821 prospective study showed that the local recurrence rate of lobectomy for stage T1 lung cancer was significantly lower than that of sublobectomy, and the survival rate was significantly higher than that of sublobectomy.
Therefore, the current standard surgical procedure for early lung cancer is still anatomical lobectomy ( Type 1 recommendation evidence)
.

②For some central lung cancer, if the surgical technique can guarantee the margin, bronchial and (or) pulmonary sleeve lobectomy has lower perioperative risk and better curative effect than pneumonectomy.
Pulmonary sleeve lobectomy is the recommended surgical procedure (Type 1 recommendation evidence)
.

③Sublobectomy is still in the clinical research stage.
Prospective multicenter randomized controlled trials comparing early lung cancer lobectomy with sublobectomy in Japan JCOG0802/WJOG4607L and North America CALGB 140503 have been enrolled, and the perioperative results showed no findings.
There is a statistically significant difference in the incidence of surgical complications or mortality between the two types of surgical resection.
The long-term follow-up results have not been announced.
At present, intentional sublobectomy is only applicable to the following situations (2B recommendation evidence): (a) The patient’s functional status cannot tolerate lobectomy; (b) Small peripheral nodules with a tumor diameter of ≤2 cm, and one of the following conditions: ground glass (GGO) component >50%; long-term follow-up tumor doubling time ≥400 d; pathology is AIS or MIA; (c) sublobectomy requirements: ensure that the resection margin is ≥2 cm or the resection margin is greater than or equal to the diameter of the lesion; anatomical segment resection is more recommended than wedge resection; unless the patient is functional Not allowed, otherwise, hilar and mediastinal lymph node sampling should also be performed (type 2B recommendation evidence)
.

(3) Surgical path: ① Thoracotomy and minimally invasive surgery have the same oncological effect.
Surgeons can choose the surgical method according to their habits and proficiency (Type 1 recommendation evidence)
.

②It has been proved that minimally invasive surgery such as thoracoscopy (including robot-assisted) is safe and feasible.
The perioperative results are better than thoracotomy, and the long-term curative effect is no less than thoracotomy
.

Therefore, thoracoscopic surgery is recommended on the premise that the surgical technique is feasible without sacrificing the principles of oncology (type 1 recommendation evidence)
.

(4) Lymph node dissection standard (2A recommendation evidence): ① Lymph node dissection and sampling are necessary components of surgery.
Routinely, at least 3 groups of mediastinal lymph nodes should be removed in whole or systematically (left side: 4L, 5, 6, and 6).
7, 8, 9 groups, 2R, 4R, 7, 8, 9 groups on the right)
.

For the number of lymph nodes to be dissected or sampled, at least 12 lymph nodes in the mediastinum + lung should be dissected or sampled
.

②As long as no lymph node metastasis is found in preoperative standard mediastinal staging (PET or EBUS, mediastinoscopy negative) for stage I to III lung cancer, lymph node dissection does not significantly upgrade the stage or bring postoperative survival advantages compared with sampling, but only before surgery For routine imaging staging (no PET or EBUS, mediastinoscopy staging), lymph node dissection is still recommended (type 1 recommendation evidence)
.

③Preoperative imaging showed that pure GGO is the main component (>50%) and intraoperative freezing is an infiltrating adenocarcinoma dominated by wall accumbens.
The probability of mediastinal lymph node metastasis is extremely low.
Selective sampling of groups 1 to 3 (left Groups 4, 5, and 7, right group 2, 4, and 7) mediastinal lymph nodes
.

Surgical resection criteria 3.
(1) Complete resection including negative margins (bronchi, artery, vein, peribronchial tissue, and tissue near the tumor)
.

Whenever there is involvement of the resection margin, unresected positive lymph nodes, or metastatic pleural effusion or pericardial effusion, it is an incomplete resection
.

(2) Complete resection is R0, incomplete resection or extracapsular infiltration of lymph nodes is found under microscope as R1, and tumor remnants that can be seen by the naked eye are R2
.

(3) The International Association for Lung Cancer has added a new definition of Run, which refers to the failure to perform lymph node dissection according to the specific drainage area of ​​the lung lobe where the tumor is located, metastasis of the mediastinal lymph node at the highest station after dissection, carcinoma in situ of the bronchial resection margin, or pleural cavity lavage cytological examination Positive, indicating that the prognosis is worse than R0 resection, and may require postoperative adjuvant treatment
.

Postoperative adjuvant treatment 4.
(1) Complete resection with negative margins (R0 resection) NSCLC follow-up treatment: ① Regular postoperative follow-up of patients at IA (T1a/b/cN0) stage (Class 1 recommendation evidence)
.

②Patients in stage IB (T2aN0) can be followed up after surgery
.

Postoperative adjuvant treatment of stage IB patients requires multidisciplinary evaluation to evaluate the benefits and risks of adjuvant chemotherapy for each patient
.

Those with high risk factors [such as poorly differentiated tumors (including neuroendocrine tumors but not well-differentiated neuroendocrine tumors), vascular invasion, visceral pleural invasion, STAS, palliative wedge resection] are recommended for postoperative adjuvant chemotherapy (2A Class recommendation evidence)
.

Patients with stage IB adenocarcinoma whose pathological subtype is mainly solid or micropapillary may also consider adjuvant chemotherapy (type 2B recommendation evidence)
.

③Platinum-based regimens are recommended for adjuvant chemotherapy for patients with stage IIA to IIB, and postoperative adjuvant radiotherapy is not recommended (type 1 recommendation evidence)
.

④For patients with EGFR-sensitive gene mutations found after stage IB to stage II, osimertinib may be used as adjuvant targeted therapy (Class 1 evidence of recommendation)
.

(2) Subsequent treatment of non-complete resection of NSCLC with positive margins: ①Patients at stage IA (T1a/b/cN0), who were found to have R1 or R2 resection during the operation, are the first choice for reoperation, and radiotherapy is also available (2B recommendation evidence)
.

②Patients with stage IB (T2aN0)/ⅡA (T2bN0) who were found to have R1 or R2 resection during the operation should be the first choice for reoperation, radiotherapy is also available, and subsequent chemotherapy depends on the situation
.

Patients with high risk factors for stage IB [such as poorly differentiated tumors (including neuroendocrine tumors but not well-differentiated neuroendocrine tumors), vascular invasion, wedge resection, visceral pleural invasion, unknown lymph node status Run] may be considered for surgery After adjuvant chemotherapy, patients with stage IB adenocarcinoma whose pathological subtype is mainly solid or micropapillary can also be considered adjuvant chemotherapy (type 2B recommendation evidence)
.

All patients with stage ⅡA should receive adjuvant chemotherapy (type 2A recommendation evidence)
.

③Patients with R1 resection in stage ⅡB can choose reoperation and postoperative adjuvant chemotherapy, or concurrent or sequential radiotherapy; R2 resection patients can choose reoperation and postoperative adjuvant chemotherapy, or concurrent radiotherapy and chemotherapy (Class 2A recommendation evidence)
.

Multiple primary cancers during the same period (Class 2B recommendation evidence) (Figure 6) 5.
(1) Diagnosis: Different pathological tissue types or different AIS; if the pathological tissue types are the same, the tumor is located in different lung lobes and there is no mediastinal lymph node metastasis
.

(2) Staging: TNM staging is performed for each lesion (type 2A recommendation evidence)
.

(3) Treatment: Surgical treatment is the first choice
.

① Give priority to the primary lesions and take into account the secondary lesions.
Try to remove the lesions as much as possible without affecting the survival of the patient and comply with the principle of tumor-free, and preserve lung function as much as possible (such as sublobectomy) (Class 2A recommendation evidence)
.

②If the secondary lesions are pure GGO, and the cardiopulmonary function cannot completely remove the lesions, it is recommended to follow up once every 6 to 12 months.
If there is no change, follow up once every 2 years (type 2A recommendation evidence)
.

Recommended radiotherapy for early NSCLC not suitable for surgery or surgery refusal 6.
Radiotherapy for early NSCLC not suitable for surgery or surgery refusal: SBRT is preferred (type 1 evidence of recommendation), indications include: (1) Early NSCLC intolerant of surgery : Advanced age, severe medical disease, stage T1～2N0M0
.

  (2) Early NSCLC that is operable but refuses surgery
.

(3) For early clinical lung cancer that cannot be performed or refused to receive pathological diagnosis, SBRT treatment can be considered when the following conditions are met: ① A clear imaging diagnosis, and the lesions increase during long-term follow-up (> 2 years) Large, or the density of ground-glass shadow increases, the proportion of solidity increases, or it is accompanied by malignant features such as vascular penetration and edge burr-like changes; at least 2 types of imaging examinations (such as chest enhanced 1～3 mm thin-layer CT and whole body PET -CT) suggest malignancy; ②After discussion and determination by the lung cancer multidisciplinary team; ③Patients and their families fully informed consent
.

(4) Relative indications: ①T3N0M0; ②simultaneous multiple primary NSCLC
.

(2) Comprehensive treatment of stage Ⅲ NSCLC patients Resectable stage Ⅲ NSCLC (Figure 7, 8) 1.
Stage Ⅲ NSCLC resectable type refers to T3N1, T4N0～1 and some T1～2N2, a small part of stage ⅢB (refers to T3N2 , N2 is a single lymph node metastasis and the diameter is less than 3 cm)
.

The role of surgery mainly depends on the resectability of the tumor
.

The model of multidisciplinary comprehensive treatment is a comprehensive treatment based on surgery
.

(1) Evaluation of surgical tolerance: The patient's cardiopulmonary function must be evaluated before surgery, and it is recommended to use electrocardiogram and pulmonary function tests for evaluation (type 1 recommendation evidence)
.

As stage IIIA patients require adjuvant therapy after surgery, whether the patient’s residual lung function can tolerate chemotherapy and radiotherapy should be considered before surgery (type 2A recommendation evidence)
.

Severe complications of other organs of the patient must be excluded before surgery, including cardiovascular and cerebrovascular events (myocardial infarction, stroke, etc.
), heart failure, arrhythmia, renal failure, etc.
within 6 months (2A recommendation evidence)
.

There are few data reports on elderly patients, and surgery should be cautious (type 2A recommendation evidence)
.

(2) Timing and method of surgery: For patients with tumors that may be completely resected, the best mode of neoadjuvant therapy has not been determined.
Whether to receive neoadjuvant therapy before surgery has no significant difference in improvement of survival, but it is recommended to receive adjuvant therapy after surgery (2B) Class recommendation evidence)
.

The surgeon can decide the timing of surgery after comprehensively assessing the patient's condition (type 2B recommendation evidence)
.

It is recommended to perform a thorough mediastinal lymph node dissection, that is, lymph nodes in groups 2R, 4R, 7, 8, and 9 on the right side, and lymph nodes in groups 4L, 5-9 on the left side (type 1 recommendation evidence)
.

It is recommended to remove the lymph nodes en bloc (type 2A recommendation evidence)
.

The principle of surgery is to preserve the lung tissue as much as possible on the basis of complete removal of the tumor (Type 1 recommendation evidence)
.

On the basis of full preoperative evaluation, depending on the extent of tumor invasion, lung lobes, compound lobes, sleeves, and pneumonectomy are feasible, and patients are recommended to carry out such operations in large hospitals with conditions (2A recommendation evidence)
.

Adjuvant platinum-containing two-drug chemotherapy is recommended for stage IIIA operable NSCLC (Class 1 evidence of recommendation)
.

Postoperative adjuvant radiotherapy is not routinely recommended.
Multidisciplinary consultation is recommended to evaluate the benefits and risks of postoperative adjuvant radiotherapy for patients with N2 stage (2B recommendation evidence)
.

For patients with EGFR-sensitive gene mutations found after surgery, osimertinib may be used as an adjuvant targeted therapy (Class 1 evidence of recommendation)
.

Unresectable stage Ⅲ NSCLC2.
Stage Ⅲ unresectable NSCLC includes the following categories: ①Multiple clusters or multi-station mediastinal lymph node metastasis on the same side [ⅢA (T1～3N2) or ⅢB (T34N2)]
.

② Contralateral hilar, mediastinal lymph node, or ipsilateral, contralateral scalene muscle or supraclavicular lymph node metastasis [ⅢB, ⅢC(T1～4N3)]
.

③It is impossible or unsuitable to remove tumors including some superior sulcus tumors [mainly refers to tumors invading vertebral body more than 50%; brachial plexus nerves, esophagus, heart or trachea, etc.
, ⅢA (T3N1, T4N0 ~ 1)]
.

The choice of treatment methods for patients with locally advanced inoperability, in addition to the need to consider tumor factors, also needs to consider the general condition of the patient and whether there is significant physical decline before treatment, as well as normal tissues and organs (such as lung, spinal cord, heart, esophagus and brachial plexus, etc.
) ) Comprehensively consider the tolerable dose of radiotherapy, and choose the dose of radiotherapy and chemotherapy according to the actual situation
.

(1) Recommended radical concurrent radiotherapy and chemotherapy (Class 1 recommendation evidence) ① Concurrent radiotherapy: (a) Radiotherapy target area: primary tumor + metastatic lymph node involving field radiotherapy, involving field radiotherapy can optimize the dose of tumor tissue and the toxicity of normal tissue Dose; PET-CT images can significantly improve the accuracy of target delineation, especially in patients with obvious atelectasis or venous enhancement contraindications
.

(B) Radiotherapy dose: The radical prescribed dose is 60-70 Gy, 2 Gy/time, and the minimum prescribed dose is at least 60 Gy, but the optimal radiation dose is still uncertain.
74 Gy is not recommended as a routine dose
.

(C) Newer radiotherapy techniques can be used to ensure the implementation of radical radiotherapy
.

Three-dimensional conformal radiotherapy and intensity modulated radiotherapy (IMRT) are routinely used in clinical practice, but IMRT is a better choice, which can reduce the occurrence of high-grade radiation pneumonia and reduce adverse reactions
.

②Platinum-based concurrent chemotherapy regimen (Class 1 recommendation evidence): (a) Etoposide + Cisplatin; (b) Vinorelbine + Cisplatin; (c) Pemetrexed + Cisplatin or carboplatin (Non-squamous cell carcinoma); (d) Paclitaxel + Cisplatin or Carboplatin
.

It is recommended to complete at least 2 cycles of chemotherapy during concurrent radiotherapy and chemotherapy
.

(2) Sequential chemoradiation if the patient cannot tolerate simultaneous chemoradiation, sequential chemoradiation is better than radiotherapy alone (Class 2A recommendation evidence)
.

The radiotherapy regimen is the same as before.
Increasing the dose of radiotherapy may improve patient survival (type 2B recommendation evidence), and the optimal dose of radiotherapy is uncertain
.

Sequential chemotherapy regimens are as follows (Class 1 recommendation evidence): ① Vinorelbine + Cisplatin; ② Paclitaxel + Cisplatin or carboplatin; ③ Pemetrexed + Cisplatin or carboplatin (non-squamous cell carcinoma)
.

It is recommended to perform radiotherapy after 2 to 4 cycles of assessment
.

(3) Induction and consolidation chemotherapy ① If the comprehensive treatment of chemotherapy and radiotherapy cannot be tolerated [the patient's general condition is poor, accompanied by medical complications, the physical fitness is significantly decreased and/or the patient's willingness], radiotherapy alone is the standard treatment (2A recommendation evidence)
.

The radiotherapy regimen is the same as the radiotherapy regimen in radical concurrent radiotherapy and chemotherapy.
Increasing the radiation dose may improve survival (type 2B recommendation evidence), and the optimal radiation dose is uncertain
.

②Although for large-burden tumors, induction chemotherapy is used to reduce tumor volume and obtain simultaneous chemotherapy and radiotherapy opportunities, but there is no evidence that induction chemotherapy can improve survival benefits (type 2A recommendation evidence)
.

③Recommend duvalizumab for consolidation therapy after concurrent chemotherapy and radiotherapy (type 1 recommendation evidence); if duvalizumab is not used for consolidation therapy, for patients who have a high potential for metastasis or whose chemotherapy has not reached a sufficient amount during the synchronization period , Consider the application of consolidation chemotherapy (type 2A recommendation evidence)
.

(3) Systemic treatment for patients with stage IV NSCLC (Figure 9) First-line treatment 1.
(1) Treatment of patients with positive non-squamous cell carcinoma driver genes and not accompanied by drug resistance gene mutations ①Patients with positive EGFR sensitive driver genes: recommended EGFR-TKI, you can choose Gefitinib, Erlotinib, Icotinib, Afatinib, Osimertinib (Type 1 recommendation evidence) or Daktinib (Patients without brain metastasis, Category 2A recommendation) Evidence), patients with brain metastases preferentially recommend osimertinib (type 2A recommendation evidence); erlotinib combined with bevacizumab (type 2A recommendation evidence), chemotherapy combined with gefitinib [function status (performance) status, PS) score is 1 to 2]; For patients with rare gene mutations such as G719X, L861Q, S768I, afatinib is recommended first
.

Patients who are found to be positive for EGFR driver genes during the first-line chemotherapy are recommended to switch to EGFR-TKI after completing conventional chemotherapy (including maintenance therapy), or to start targeted therapy after stopping chemotherapy (type 2A recommendation evidence)
.

②Patients with positive ALK fusion gene: aletinib, ceritinib, crizotinib can be selected (type 1 recommendation evidence)
.

Patients who are found to be ALK fusion gene positive during the first-line chemotherapy are recommended to complete conventional chemotherapy, including switching to targeted therapy after maintenance therapy or starting targeted therapy after stopping chemotherapy (type 2A recommendation evidence)
.

③Patients with positive ROS1 fusion gene: Crizotinib is recommended for first-line treatment of patients with positive ROS1 fusion gene (Type 1 recommendation evidence), platinum-containing dual-agent chemotherapy or platinum-containing dual-agent chemotherapy + bevacizumab (2A) Class evidence)
.

Other non-classical mutations can receive platinum-containing dual-drug chemotherapy or participate in clinical trials
.

(2) Treatment of patients with negative non-squamous cell carcinoma driver genes: For patients with positive PD-L1 expression (≥1%), pembrolizumab can be used as a single agent, but PD-L1 expression is high (≥50%) The benefit of patients is more obvious
.

①Patients with a PS score of 0 to 1: (a) Recommend pemetrexed + carboplatin or cisplatin combined with pembrolizumab chemotherapy (type 1 recommendation evidence); or pemetrexed + carboplatin + carrelizumab Monoclonal antibody (type 2A recommendation evidence); or pemetrexed + carboplatin + sintilimab (type 2A recommendation evidence); or platinum-containing two-drug combination chemotherapy, chemotherapy for 4 to 6 cycles, platinum-based Choose carboplatin or cisplatin, lobaplatin, and the drugs used in combination with platinum include pemetrexed, paclitaxel, paclitaxel liposomes, gemcitabine or docetaxel (type 1 recommendation evidence); pemetrexed combined with cisplatin It can significantly prolong the survival time of patients, and is superior to gemcitabine combined with cisplatin in terms of efficacy and reduction of adverse reactions (2A recommendation evidence); for patients who are not suitable for platinum drug treatment, non-platinum two-drug combination chemotherapy can be considered, including Gemcitabine combined with vinorelbine or gemcitabine combined with docetaxel (type 1 recommendation evidence)
.

(B) For patients with no contraindications, bevacizumab or recombinant human endostatin can be used in combination with chemotherapy and maintenance therapy (type 1 or 2A recommendation evidence), paclitaxel and carboplatin are recommended options (1 Contraindications include central lung cancer, recent active bleeding, thrombocytopenia, uncontrollable hypertension, nephrotic syndrome, arterial thromboembolic events, congestive heart failure, anticoagulation therapy, etc.

.

②Patients with a PS score of 2 points: Single-drug therapy is recommended
.

Compared with the best supportive treatment, single-agent chemotherapy can prolong the survival time of patients and improve the quality of life
.

Optional single drugs include gemcitabine, vinorelbine, paclitaxel, docetaxel, and pemetrexed (type 2A recommendation evidence)
.

③Patients with a PS score of 3 to 4: Chemotherapy with cytotoxic drugs is not recommended
.

Such patients generally cannot benefit from chemotherapy, and it is recommended to use the best supportive treatment or participate in clinical trials
.

④Patients with 4 to 6 cycles of first-line chemotherapy to achieve disease control (complete remission, partial remission and stability), good PS score and good chemotherapy tolerance can choose maintenance treatment
.

The drugs for maintenance treatment with the same drug are pembrolizumab + pemetrexed, carrelizumab + pemetrexed, sintilizumab + pemetrexed, pemetrexed, gemcitabine or beva Rizumab (type 1 recommendation evidence); the drug for maintenance treatment is pemetrexed (type 1 recommendation evidence)
.

(3) Treatment of patients with negative squamous cell carcinoma driver genes: For patients with positive PD-L1 expression (≥1%), pembrolizumab can be used as a single agent, but with high PD-L1 expression (≥50%) The patient benefit is more obvious
.

 ①Patients with a PS score of 0 to 1: We recommend paclitaxel combined with carboplatin combined with pembrolizumab chemotherapy (type 1 recommendation evidence), and paclitaxel combined with carboplatin combined with tislelizumab can also be used
.

A platinum-containing two-drug combination regimen can be used for chemotherapy, with 4 to 6 cycles of chemotherapy.
Platinums can choose carboplatin, cisplatin, lobaplatin or nedaplatin.
Drugs used in combination with platinum include paclitaxel, paclitaxel liposomes, Gemcitabine, docetaxel (Class 1 recommendation evidence), or albumin paclitaxel; for patients who are not suitable for platinum drug treatment, non-platinum two-drug combination chemotherapy may be considered, including gemcitabine combined with vinorelbine or gemcitabine combined with doceta Match
.

②Patients with a PS score of 2 points: Single-agent chemotherapy is recommended
.

Compared with the best supportive treatment, single-agent chemotherapy can prolong survival time and improve the quality of life.
The available single drugs include gemcitabine, vinorelbine, paclitaxel, and docetaxel (Class 2A recommendation evidence)
.

③Patients with a PS score of 3 to 4: It is recommended to adopt the best supportive treatment or participate in clinical trials
.

④Patients with 4 to 6 cycles of first-line chemotherapy to achieve disease control (complete remission, partial remission and stability), good PS score and good chemotherapy tolerance can choose maintenance treatment
.

The drugs for maintenance therapy with the same drug are gemcitabine and tislelizumab (type 1 recommendation evidence), and docetaxel (type 2A recommendation evidence) can also be selected
.

(4) Treatment of patients with positive squamous cell carcinoma driver genes ①Although the EGFR mutation rate of adenocarcinoma in advanced NSCLC is significantly higher than that in non-adenocarcinoma, the results of EGFR mutation detected in non-adenocarcinoma support EGFR detection for all NSCLC patients
.

It is recommended to perform EGFR, ALK, and ROS1 gene testing in patients with non-smokers, small specimens, or mixed type squamous cell carcinoma (Class 2A recommendation evidence)
.

②The treatment of patients with positive EGFR driver gene, ALK fusion gene and ROS1 fusion gene in squamous cell carcinoma was the same as the treatment of patients with positive non-squamous cell carcinoma driver gene
.

Second-line and back-line treatment 2.
First, actively encourage back-line patients to participate in clinical trials of new drugs
.

(1) Treatment of patients with positive non-squamous cell carcinoma driver genes ① Patients with stage IV non-squamous cell carcinoma with positive EGFR driver genes: If EGFR-TKI is not used in the first-line treatment, it is recommended to use EGFR-TKI first in the second-line treatment (Class 1 evidence of recommendation) )
.

Patients with disease progression after first-line use of EGFR-TKI are classified into slow progression type, local progression type, and rapid progression type according to the type of progression
.

(A) If it is a slowly progressing type, it is recommended to continue the original EGFR-TKI treatment (type 2A recommendation evidence)
.

After treatment progresses again, a second biopsy is recommended to detect the T790M mutation status
.

(B) If it is a locally advanced type, it is recommended to continue the original EGFR-TKI treatment + local treatment (type 2A recommendation evidence)
.

After treatment progresses again, a second biopsy is recommended to detect the T790M mutation status
.

(C) If it is a rapidly progressing type, a second biopsy is recommended to detect the mutation status of T790M.
For those who are T790M positive, osimertinib (type 1 recommendation evidence) or ametinib and vometinib are recommended (type 2A recommendation evidence) ), T790M-negative patients recommend platinum-containing dual-drug chemotherapy (Class 1 evidence of recommendation)
.

If T790M status is not tested, platinum-containing dual-drug chemotherapy is recommended
.

The third-line PS score of 0 to 2 can accept single-agent chemotherapy or recommend the use of Anlotinib without contraindications (type 2A recommendation evidence)
.

② Patients with stage IV non-squamous cell carcinoma with positive ALK fusion gene: If ALK-TKI is not used in the first-line treatment, it is recommended to use ALK-TKI first in the second-line treatment, or use platinum-containing dual-drug chemotherapy (Class 1 recommendation evidence)
.

For patients with disease progression in first-line crizotinib treatment, if they progress slowly, they can continue to take crizotinib (Class 2A recommendation evidence); if they are locally advanced, it is recommended to continue oral crizotinib + topical therapy (Class 2A) (Recommendation evidence); For those with rapid progress, we recommend treatment with aletinib or ceritinib or ensatinib (type 1 recommendation evidence), and platinum-containing dual-agent chemotherapy (type 2A recommendation evidence) is also acceptable
.

In the absence of contraindications, anlotinib can be used in the third line (type 2A recommendation evidence)
.

③ Patients with stage IV non-squamous cell carcinoma with positive ROS1 gene rearrangement: If crizotinib is not used in the first-line treatment, it is recommended to use crizotinib first in the second-line treatment (type 2A recommendation evidence)
.

If the first-line patients progressed after receiving crizotinib, it is recommended to receive platinum-containing dual-drug chemotherapy (type 2A recommendation evidence)
.

In the absence of contraindications, anlotinib is recommended for the third-line (type 2A recommendation evidence)
.

④Platinib can be used for patients with stage IV non-squamous cell carcinoma with positive RET fusion gene after platinum chemotherapy has progressed
.

(2) Treatment of patients with negative driver genes for non-squamous cell carcinoma.
PS score 0 to 2 points.
After first-line progression of patients with negative driver genes for non-squamous cell carcinoma, nivolumab is recommended for second-line treatment if they have not received immunotherapy (1 Class recommendation evidence)
.

PS score 0-2 points to drive gene-negative non-squamous cell carcinoma patients can also use docetaxel (type 1 recommendation evidence) or pemetrexed (type 2A recommendation evidence) single-agent chemotherapy after first-line progression
.

For patients with a PS score> 2 points, the second-line recommends the best supportive treatment
.

If you have not used pemetrexed or docetaxel monotherapy in the previous stage, you can receive pemetrexed or docetaxel monotherapy as a third-line treatment (type 2A recommendation evidence), or recommend it if there are no contraindications Anlotinib (Class 2A recommendation evidence), the best supportive treatment is recommended later
.

(3) Treatment of patients with positive squamous cell carcinoma driver genes For patients with stage IV squamous cell carcinoma with positive EGFR driver genes, if EGFR-TKI is not used in the first-line treatment, it is recommended to use EGFR-TKI first in the second-line treatment (2B recommendation evidence)
.

If the disease progresses after first-line use of EGFR-TKI, refer to the treatment of patients with positive non-squamous cell carcinoma driver genes
.

The third-line recommends single-agent chemotherapy, or recommends anlotinib if there are no contraindications (type 2A recommendation evidence)
.

(4) Treatment of patients with negative squamous cell carcinoma driver gene.
PS score 0 to 2 points.
After first-line progression of patients with negative driver gene squamous cell carcinoma, if they have not received immunotherapy, nivolumab is recommended as second-line therapy (Class 1 recommendation) Evidence)
.

Patients with a PS score of 0 to 2 driving gene-negative squamous cell carcinoma can also be treated with single-agent chemotherapy with docetaxel after first-line progression (Class 1 evidence of recommendation)
.

For patients with a PS score> 2 points, the best supportive treatment is recommended for the second and later lines
.

The third line recommends the use of Anlotinib without contraindications (type 2A recommendation evidence)
.

For patients receiving moderate and high febrile neutropenia risk chemotherapy regimens, the prophylactic use of recombinant human granulocyte colony stimulating factor or pegylated recombinant human granulocyte colony stimulating factor may be considered
.

(4) Treatment of oligometastasis in patients with stage IV NSCLC with oligometastasis is divided into simultaneous oligometastasis and metachronous oligometastasis
.

Simultaneous oligometastasis refers to oligo metastases that have appeared at the time of initial diagnosis, and metachronous oligometastasis refers to oligo metastases that have appeared for a period of time after treatment
.

After effective systemic treatment for patients with oligometastasis of NSCLC, local treatments such as radiotherapy and surgery can bring clinical benefits, and a multidisciplinary comprehensive treatment strategy can maximize the benefits of patients with oligometastasis of lung cancer
.

For patients with isolated organ (brain, adrenal gland or bone) metastases before lung surgery, surgery or radiotherapy and postoperative treatment should be performed according to the principles of lung disease staging
.

The treatment of solitary organ metastases is performed according to the location: (1) Active local treatment for brain or adrenal metastases, including surgical removal of brain or adrenal metastases, or conventional radiotherapy/SBRT for brain or adrenal metastases (Class 2A recommended evidence )
.

If the patient has obvious central nervous system symptoms, imaging examinations suggest that there is significant compression and edema of brain metastases or severe neutral structure deviation, etc.
, it is recommended to perform brain metastasis surgery first to relieve the brain problem, and then choose the primary lung tumor.
Surgery (Type 2A recommendation evidence)
.

(2) Patients with bone metastases receive radiotherapy combined with bisphosphonate therapy
.

For weight-bearing bone metastases, surgery and radiotherapy are recommended for metastases (Class 2A recommendation evidence)
.

If a solitary organ (brain, adrenal gland, or bone) metastases occurs after lung surgery, treatment should be based on the location of the solitary organ metastasis
.

(1) Patients with brain metastases or adrenal metastases should be actively treated locally, including surgical removal of brain or adrenal metastases, or routine radiotherapy/SBRT for brain or adrenal metastases, combined with systemic therapy according to the situation (Class 2A recommendation evidence)
.

(2) Patients with bone metastases receive radiotherapy combined with bisphosphonate therapy
.

For patients with weight-bearing bone metastases, it is recommended that metastasis surgery plus radiotherapy, combined with systemic therapy according to the situation (type 2A recommendation evidence)
.

In short, for patients with oligometastatic advanced NSCLC, on the basis of systemic standard treatment, active local treatment should be adopted to maximize the survival benefit of patients
.

(5) Treatment of SCLC and LCNEC Treatment of SCLC patients 1.
(1) Treatment of patients with limited-stage SCLC (Figure 10) ① Treatment of patients with operable limited-stage SCLC (T1～2N0): After systematic staging examination, there is no indication For patients with T1～2N0 with mediastinal lymph node metastasis, radical surgery is recommended.
The surgical procedure is lobectomy + hilar and mediastinal lymph node dissection (type 2A recommended evidence); patients with postoperative pathology suggesting N0 are recommended for adjuvant chemotherapy, and the plan includes reliance Poside + cisplatin, etoposide + carboplatin (2A recommendation evidence); patients with N1 and N2 suggested by postoperative pathology, adjuvant chemotherapy combined with thoracic radiotherapy (2A recommendation evidence) is recommended, either simultaneously or sequentially
.

The adjuvant chemotherapy regimen recommends etoposide + cisplatin (Class 1 evidence of recommendation)
.

It is possible to decide whether to perform prophylactic cranial irradiation (PCI) according to the actual situation of the patient (Type 1 recommendation evidence)
.

②Treatment of patients with inoperable limited-stage SCLC (exceeding T1～2N0 or inoperable T1～2N0): (a) Patients with PS score 0～2: Chemotherapy combined with chest radiotherapy is the standard treatment (Type 1 recommendation evidence)
.

The chemotherapy regimens were etoposide + cisplatin (type 1 recommendation evidence) and etoposide + carboplatin (type 1 recommendation evidence)
.

Chest radiotherapy should be intervened as soon as possible during the first to second cycles of chemotherapy
.

If the patient cannot tolerate it, sequential chemoradiation is also feasible
.

The optimal dose and schedule of radiotherapy have not yet been determined.
The recommended total dose of chest radiotherapy is 45 Gy, 1.
5 Gy/time, 2 times/d, 3 weeks; or the total dose is 60-70 Gy, 1.
8-2.
0 Gy/time, once/time.
d, 6 to 8 weeks
.

For special clinical conditions, such as huge tumors, pulmonary dysfunction, obstructive atelectasis, etc.
, radiotherapy can be considered after 2 cycles of chemotherapy
.

Patients who have achieved complete or partial remission after radiotherapy and chemotherapy may be considered for PCI (type 2A recommendation evidence)
.

(B) Eastern Cooperative Oncology Group (ECOG) PS score 3 to 4 (due to SCLC) patients: Various factors should be fully considered, and treatment options should be carefully selected, such as chemotherapy (single-drug regimen or Combined reduction plan), if the PS score can reach 2 points or less after treatment, simultaneous or sequential radiotherapy can be considered.
If the PS score still cannot be restored to less than 2 points, it is determined whether to use chest radiotherapy according to the specific situation
.

Patients who have achieved complete or partial remission after radiotherapy and chemotherapy may be considered for PCI (type 2A recommendation evidence)
.

(C) Patients with an ECOG PS score of 3 to 4 (not caused by SCLC): Recommend the best supportive treatment
.

(2) First-line treatment of patients with extensive-stage SCLC (Figure 11) ①Treatment of patients with extensive-stage SCLC with asymptomatic or no brain metastasis: (a) Patients with an ECOG PS score of 0 to 2: Recommended combination of etoposide and carboplatin Ticlizumab (Class 1 evidence of recommendation) or chemotherapy
.

The ECOG PS score is 3 to 4 points (caused by SCLC), and chemotherapy is recommended
.

Plans include EP plan (etoposide + cisplatin) (type 1 recommendation evidence), EC plan (etoposide + carboplatin) (type 1 recommendation evidence), IP plan (irinotecan + cisplatin) (type 1 recommendation) Evidence), IC plan (Irinotecan + Carboplatin) (Type 1 recommendation evidence), Etoposide + Loplatin (Type 2A recommendation evidence)
.

For patients who have achieved complete or partial remission after chemotherapy, if the distant metastases are controlled and the general condition is good, chest radiotherapy can be added (2A recommendation evidence); PCI should be carefully selected as appropriate (2A recommendation evidence)
.

(B) Patients with an ECOG PS score of 3 to 4 (not caused by SCLC): recommend the best supportive treatment
.

②Treatment of SCLC patients with extensive local symptoms: (a) Superior vena cava syndrome: radiotherapy followed by chemotherapy is recommended for patients with severe clinical symptoms (class 2A recommendation evidence); for patients with mild clinical symptoms, chemotherapy followed by radiotherapy is recommended (class 2A recommendation) Evidence), and give symptomatic treatments such as oxygen inhalation, diuresis, sedation, and pain relief at the same time
.

The radiation field of local radiotherapy should include the primary tumor, the entire mediastinum area and the two supraclavicular areas, and the superior vena cava should be included in the radiation field; local edema may increase in the early stage of radiotherapy, and hormone and diuretic adjuvant treatment can be used if necessary; for the first time; Chemotherapy should be shocking
.

After radiotherapy and chemotherapy, PCI is determined according to the specific situation of the patient (type 2A recommendation evidence)
.

(B) Spinal cord compression: If there are no special circumstances, the patient should first receive local radiotherapy to control the symptoms of compression, and be given EP, EC, IP or IC chemotherapy (Class 2A recommendation evidence)
.

Because patients with spinal cord compression have a shorter survival time and poor quality of life, the choice of chest radiotherapy and PCI requires comprehensive consideration of multiple factors and careful selection (for example, patients with complete or partial remission can be treated with radiotherapy), but surgery is generally not recommended Decompression therapy
.

(C) Bone metastasis: Recommend EP, EC, IP or IC chemotherapy + local palliative external beam radiotherapy ± bisphosphonate therapy (2A recommended evidence); orthopedic fixation can be used for patients at high risk of fracture
.

(D) Obstructive atelectasis: Recommend EP regimen, EC regimen, IP regimen or IC regimen chemotherapy + chest radiotherapy (2A recommendation evidence)
.

Radiotherapy after 2 cycles of chemotherapy is reasonable.
It is easy to clarify the scope of the lesion, reduce the irradiation volume, and enable the patient to tolerate and complete the radiotherapy
.

③Treatment of patients with brain metastases: (a) Asymptomatic patients with brain metastases: receive whole-brain radiotherapy after systemic chemotherapy (Class 2A recommendation evidence).
Patients with complete or partial remission after treatment can be given chest radiotherapy (Class 2A) Recommended evidence)
.

(B) Patients with symptomatic brain metastases: Whole-brain radiotherapy and chemotherapy are recommended to be performed sequentially (2A recommendation evidence).
Patients with complete or partial remission after treatment can be given chest radiotherapy (2A recommendation evidence)
.

(3) PCI of SCLC patients should fully communicate with patients and family members when making PCI treatment decisions, and determine the pros and cons according to the specific conditions of the patients
.

For limited-stage SCLC with complete resection, the decision to accept PCI is based on the actual situation (type 2A recommendation evidence); for limited-stage SCLC with complete remission or partial remission, PCI is recommended (type 2A recommendation evidence); for extensive-stage SCLC, discretionary Consider PCI (Type 2A recommendation evidence)
.

PCI is not recommended for patients who are older than 65 years old, have severe comorbidities, PS scores greater than 2 points, and have impaired neurocognitive function
.

PCI should start about 3 weeks after the end of chemotherapy and radiotherapy.
Brain-enhanced MRI should be performed before PCI
.
If no brain metastasis is confirmed, PCI can be started .

The dose of PCI is 25 Gy, which is done in 10 splits within 2 weeks
.

(4) Second-line treatment (Figure 12) ①Patients who relapsed within 6 months after first-line treatment with an ECOG PS score of 0 to 2: It is recommended to choose intravenous or oral topotecan chemotherapy (type 2A recommendation evidence), and patients can also be recommended to participate in the clinic Trial or choose the following drugs, including irinotecan (2A recommendation evidence), paclitaxel (2A recommendation evidence), docetaxel (2A recommendation evidence), vinorelbine (2A recommendation evidence), gemcitabine (2A recommendation evidence) Recommendation evidence), temozolomide (2A recommendation evidence), cyclophosphamide combined with doxorubicin and vincristine (2A recommendation evidence)
.

Patients with an ECOG PS score of 2 can reduce the dose or apply growth factor supportive treatment as appropriate
.

②Patients who relapse more than 6 months after first-line treatment: choose the original first-line treatment plan
.

(5) Oral Anlotinib is recommended for third-line treatment (Class 1 evidence of recommendation)
.

(6) Treatment of elderly SCLC patients.
For elderly SCLC patients, the treatment plan cannot be determined based on age alone
.
It is more meaningful to guide treatment according to the functional state of the body .

If elderly patients have the ability to take care of themselves in daily life, are in good physical condition, and have relatively good organ functions, they should receive standard combined chemotherapy (radiotherapy if indicated).
However, elderly patients may suffer from bone marrow suppression, fatigue, and impaired organ function.
The probability is higher, so it should be closely observed during treatment to avoid excessive risks
.

Treatment of pulmonary LCNEC patients 2.
The incidence of pulmonary LCNEC is low, accounting for 3% of lung cancer.
At present, there is no unified treatment standard.
It is recommended to refer to the treatment principle of non-squamous NSCLC.
Medical treatment can be treated with etoposide + platinum regimen.
(Type 2B recommendation evidence)
.

6.
Follow-up (1) Stage I to II (the initial treatment is surgery ± chemotherapy or after SBRT treatment) and after surgical resection of stage IIIA NSCLC R0, there are no clinical symptoms or stable symptoms
.

1.
The first 3 years: 1 follow-up for 3 to 6 months; evaluation of smoking status (encourage patients to quit smoking); medical history, physical examination, chest CT±enhanced scan
.

2.
In the 4th and 5th years: follow-up once a year; evaluation of smoking status (encourage patients to quit smoking); medical history, physical examination, chest CT±enhanced scan
.

3.
More than 5 years: follow up once a year; evaluation of smoking status (encourage patients to quit smoking); medical history and physical examination; low-dose non-enhanced chest CT (type 2B recommendation evidence)
.

(2) Locally advanced NSCLC (inoperable stage ⅢA and ⅢB) after radiotherapy and chemotherapy, without clinical symptoms or stable symptoms
.

1.
In the first 3 years: follow-up every 3-6 months; evaluation of smoking status (encourage patients to quit smoking); medical history, physical examination, CT±enhanced scan of chest and abdomen (enhanced scan is best at 12 and 24 months)
.

2.
In the 4th and 5th years: follow-up once every 6 months; medical history, physical examination, CT±enhanced scan of chest and abdomen
.

3.
More than 5 years: follow-up once a year; medical history, physical examination, enhanced CT of the chest and abdomen (type 2B recommended evidence)
.

(3) After the end of systemic treatment for patients with stage IV NSCLC
.

1.
Those with no clinical symptoms or stable symptoms: follow-up once every 8-12 weeks; medical history, physical examination, enhanced CT of the chest and abdomen; patients with brain and bone metastases need to review brain MRI and whole body bone scan; participants in clinical trials , Follow-up should follow the clinical research protocol
.

2.
New clinical symptoms and/or symptoms aggravated: Follow up immediately, and whether to perform CT or MRI examinations is determined by the clinician (2B recommendation evidence)
.

The Chinese Medical Association's Lung Cancer Clinical Diagnosis and Treatment Guidelines emphasize the standardization and accessibility of diagnosis and treatment measures for lung cancer screening, diagnosis, pathology, treatment, and follow-up in the country.
Based on the applied drugs, combined with the latest basic research reports on lung cancer diagnosis and treatment by Chinese experts published at international conferences and the academic progress made by Chinese lung cancer experts in the past year, the guidelines were finally formed
.

Chinese Medical Association Lung Cancer Clinical Diagnosis and Treatment Guidelines (2021 Edition) Expert Committee Advisors, Academic Secretary, etc.
Conflict of Interest All authors declare that there is no conflict of interest (Received Date: 2021-02-07) The content is reproduced from: Chinese Journal of Oncology