Adenocarcinoma of the lungs

by



OVERVIEW

是非小细胞肺癌的主要类型之一，多数起源于支气管黏膜上皮
早期缺乏特异性表现，可有咳嗽、痰中带血或咯血、喘鸣、胸痛等症状
与多种因素相关，吸烟及室内空气污染等有关
手术是肺腺癌的首选治疗方法，多采取综合治疗与个性化治疗相结合的方法

Definition

  • Lung adenocarcinoma is a malignant epithelial tumor with glandular tubular differentiation or mucus secretion, mostly originating from the bronchial mucosal epithelium.
  • It is one of the main types of non-small cell lung cancer and the most common type of lung cancer in China, especially in women and non-smokers.
  • It usually occurs in the right lung more than the left lung, and the upper lobe more than the lower lobe. Most of them occur in the peripheral part of the lungs, but they can also be centralized and even located in the bronchial tubes.

    • Staging

    Lung adenocarcinoma belongs to one of the pathologic types of lung cancer, on the basis of which it can be further typed according to the status of the driver genes, etc., which can help in the development of treatment plans and prognostic assessments, etc.

    Molecular typing

    Important genes related to cancer development are called driver genes, and currently the main driver genes studied in lung cancer include EGFR, ALK, ROS1, BRAF, NTRK, MET, RET, KRAS, and HER-2.

    Targeted therapy against driver gene variants has gradually become the main treatment for lung cancer, especially lung adenocarcinoma, and has achieved remarkable efficacy.

    EGFR突变型肺癌

    This type can generally be treated with EGFR-TKIs (tyrosinase inhibitors), including molecularly targeted drugs such as gefitinib, erlotinib, erlotinib, eketinib, afatinib, daclatinib, and ositinib.

    For more information, please refer to reading EGFR mutant lung cancer.

    ALK融合型肺癌

    This type can be treated with molecularly targeted drugs such as alectinib, crizotinib and ceritinib.

    For more information, please refer to ALK fusion type lung cancer.

    ROS1融合型肺癌

    This type of lung cancer can be treated with molecular targeted drugs such as crizotinib.

    For more information, please refer to ROS1 fusion lung cancer.

    其他分子分型

    In addition to the above molecular typing, some molecular typing has been gradually proposed, such as BRAF, NTRK, MET, RET, KRAS, HER-2 and other genes.

  • Advanced lung cancer patients with MET14 exon skipping mutation cannot tolerate chemotherapy and can use cevotinib.
  • Patients with BRAF V600 mutation-positive advanced lung cancer can use dabrafenib in combination with trametinib.

    • Histologic typing

    According to the World Health Organization (WHO) lung tumor classification, lung adenocarcinoma is classified into pre-invasive lesions, minimally invasive adenocarcinoma and invasive adenocarcinoma.

    Among them, pre-invasive lesions belong to the category with the best prognosis, and after treatment, they can survive for a long time without even affecting normal life expectancy.

    Invasive adenocarcinoma, which can be considered as true lung adenocarcinoma, is generally referred to as invasive adenocarcinoma if not otherwise specified.

    浸润前病变
  • Atypical adenomatous hyperplasia (AAH): first found in primary lung cancer, especially around lung adenocarcinoma, and occasionally found in lung tissue.AAH is the earliest pre-invasive lesion, usually ≤0.5 cm.
  • Adenocarcinoma in situ (AIS): an important starting point in the development of lung adenocarcinoma, which can be categorized into non-mucinous and mucinous types.
    • 微浸润性腺癌（MIA）
  • The lesion contains tiny infiltrating adenocarcinoma.
  • Usually ≤3 cm.
  • Can be categorized into non-mucinous and mucinous types.
  • Infiltrative structures refer to vesicular, papillary, solid and micropapillary adenocarcinoma components.
    • 浸润性腺癌

    According to the cellular and histologic features of adenocarcinoma, it can be divided into the following five subtypes.

  • Ependymal adenocarcinoma: this type accounts for about 3.9% of invasive adenocarcinomas, with few lymph node metastases and less frequent pleural invasion.
  • Alveolar adenocarcinoma: it is the most common subtype of invasive lung adenocarcinoma, accounting for about 37%, and is prone to pleural invasion and has a high rate of lymph node metastasis.
  • Papillary adenocarcinoma: more common in invasive lung adenocarcinoma, accounting for about 29%.
  • Micropapillary adenocarcinoma: it is generally believed that this type has strong invasive behavior and is prone to pleural invasion and lymph node metastasis.
  • Solid adenocarcinoma: this type is poorly differentiated and highly malignant.

    • Special reminder: the above subtypes usually exist in combination, i.e., they are mostly mixed subtypes.

    Classification according to the site of occurrence

    According to the site of lung adenocarcinoma, it can be divided into the following two types.

  • Central type lung adenocarcinoma: the tumor occurs in the bronchial tubes above the opening of segmental bronchioles, which is less common. It has more clinical symptoms and the accuracy of fiberoptic bronchoscopy and sputum cytology is higher, but the difficulty of surgery is often greater than that of peripheral type.
  • Peripheral type lung adenocarcinoma: the tumor occurs in the bronchial tubes below the segmental bronchial openings, i.e. from the subsegmental bronchioles to the alveoli. It is relatively common in lung adenocarcinoma.

    • Morbidity

    Disease Overview

  • Adenocarcinoma accounts for 40%～55% of lung cancer, and is the most common type of lung cancer in China.
  • According to statistics, among primary lung adenocarcinomas, invasive adenocarcinoma accounts for about 85%.

    • Prevalent population

  • The ratio of male to female is 1:1.32, and the age is 17-84 years old, with an average age of 59 years old.
  • According to statistics, non-smoking lung adenocarcinoma patients account for the majority of lung cancers, while lung adenocarcinoma only accounts for a minority of smokers, and more are squamous lung cancers.

    • Focus on

    About Diagnosis

    Lung adenocarcinoma is diagnosed mainly by cytologic or histologic pathologic examination.

    Gene mutation testing is generally recommended for patients with lung adenocarcinoma, which helps to understand the molecular typing of their driver genes, thus preparing them for subsequent targeted therapy.

    About treatment and prognosis

    The treatment of lung adenocarcinoma needs to be decided according to the patient’s physical condition, the pathological and histological type and molecular typing of the tumor, the extent of invasion and the tendency of development, and other factors, and generally adopts the mode of multidisciplinary comprehensive treatment.

  • Stage I and II lung adenocarcinoma patients
    • 主要采取根治性手术切除的治疗方法，部分患者需要术后进行辅助化疗或靶向治疗。无法手术的患者，可选用根治性放疗±化疗的治疗方案。
    Ⅰ期和Ⅱ期属于早期阶段，经过积极规范治疗后，大部分患者都可能获得正常的自然寿命。
  • Stage III lung adenocarcinoma belongs to the locally advanced stage, some patients still have the opportunity of surgical treatment, and after surgery, supplemented with chemotherapy, radiotherapy, targeted therapy and other comprehensive treatments, they can still get better treatment effect, further prolong the survival period of patients and improve the quality of life.
  • Stage III inoperable patients, as well as stage IV patients, through targeted therapy, radiotherapy and immunotherapy and other integrated treatment, may also be able to obtain a long survival and improve the quality of life, it is recommended to actively accept standardized treatment.

    • Causes

    Causes

    The etiology of lung adenocarcinoma is not different from that of lung cancer, which is still not completely clear. From the perspective of lung cancer, it may be related to the following factors.

    Smoking and passive smoking

  • Long-term heavy smoking is the most important causative factor of lung cancer. The higher the amount of smoking, the longer the duration of smoking, and the younger the age of starting smoking, the higher the risk of lung cancer.
  • Passive smoking is also a risk factor for lung cancer and is mainly seen in women.
  • The prevalence of lung cancer can be reduced when smokers quit smoking.

    • Occupational exposure

  • Carcinogenic substances such as asbestos, chromium, nickel, copper, tin, arsenic and radioactive substances are present in the working environment.
  • Long-term exposure to the above carcinogenic substances can lead to an increased risk of lung cancer.

    • Air pollution

  • Outdoor pollution: industrial exhaust, automobile exhaust, haze, etc., containing carcinogens identified by the World Health Organization as Class A carcinogens.
  • Indoor microenvironmental pollution: soot from indoor coal burning, kitchen oil smoke, carcinogens released by indoor decoration materials, etc.

    • Diet and Physical Activity

  • Some studies show that low intake of fruits and vegetables in adulthood is associated with an elevated risk of lung cancer.
  • People with low serum level of beta carotene have high risk of lung cancer.
  • Some studies have shown that long-term moderate to vigorous physical activity reduces the risk of lung cancer by 13% to 30%.

    • Radioactive factors

  • Natural stone containing radioactive elements such as radon, such as granite, brick sand, cement and plaster. Radioactive particles decaying from radon can cause radiation damage in the human respiratory system, leading to lung cancer.
  • Large dose of ionizing radiation is also a causative factor of lung cancer.

    • Heredity and gene

  • Family aggregation: there is family aggregation among lung cancer patients, if there are lung cancer patients or other malignant tumors patients in the family, their relatives have increased risk of developing lung cancer.
  • Gene mutation: Abnormalities in gene structure and function, such as EGFR mutation gene and ALK fusion gene, are closely related to lung cancer.

    • Other factors

  • The American Cancer Society lists tuberculosis as one of the factors in the development of lung cancer. The risk of lung cancer in patients with tuberculosis is 10 times higher than that in the normal population, and the main histologic type is adenocarcinoma.
  • Certain chronic lung diseases, such as chronic obstructive pulmonary disease, tuberculosis, idiopathic pulmonary fibrosis, scleroderma, viral infections, and fungal toxins (aflatoxins), may also have a relationship with the development of lung cancer.

    • Pathogenesis

    The etiology of lung adenocarcinoma is still not completely clear. In terms of pathological evolution and driver genes, the following pathogenesis may exist.

    Pathologic evolution

  • Linear developmental pattern: atypical adenomatous hyperplasia → adenocarcinoma in situ → microinvasive adenocarcinoma → invasive lung adenocarcinoma.
  • Most lung adenocarcinomas have the above pathologic changes, but other developmental patterns cannot be ruled out.

    • Mechanisms related to driver genes

  • Driver genes are important genes associated with cancer development. In lung adenocarcinoma, the main driver genes that have been studied include EGFR mutation, ALK fusion and ROS1 fusion.

    • Driver genes usually have a transforming effect, which can initiate the evolution of non-cancerous cells to malignant tumors, which can induce lung adenocarcinoma and contribute to its progression.

    表皮生长因子受体（EGFR）
  • EGFR is a tyrosine kinase-type receptor that forms a dimer upon activation by ligands, activating its intracellular kinase pathway, which in turn activates downstream signaling pathways, thereby promoting cell survival and proliferation.
  • Mutations or overexpression of the EGFR gene encoding the EGFR receptor are associated with tumor cell proliferation, tumor invasion, metastasis and inhibition of apoptosis.
    • 间变淋巴瘤激酶基因（ALK）
  • Mutations in ALK are mainly the occurrence of breakage rearrangement of ALK gene and other genes to form a fusion gene.
  • It has been found that ALK fusion proteins are more common in younger lung adenocarcinoma patients, especially those younger than 30 years old.
    • 活性氧1（ROS1）
  • ROS1 gene rearrangement is a newer molecular subtype of lung cancer, and its mutation and activation pathway are similar to that of ALK, which is present in about 1% to 2% of patients with lung adenocarcinoma.

    • Symptoms

  • Symptoms of lung adenocarcinoma are not significantly different from those of other types of lung cancer, and it is not possible to determine the specific type of lung cancer by symptoms.
  • Early stage usually has no obvious symptoms, and symptoms appear only when the disease develops to a certain stage, and the symptoms are related to the site of tumor, size, type, whether it infringes or compresses the neighboring organs, and whether it has metastasis or not.

    • Special reminder: Lung adenocarcinoma is a type of lung cancer that can only be confirmed by pathological examination, and it is generally difficult to identify it by symptoms, therefore, the following are the symptoms that often appear in lung cancer patients.

    Primary symptoms

    Cough and sputum

  • Cough is the most common symptom when lung cancer patients visit doctor, more than half of patients have cough symptoms when they visit doctor.
  • Most of them have irritating dry cough with no sputum or a little white mucus sputum.

    • Hemoptysis

  • About 40% of lung cancer patients will have hemoptysis symptoms.
  • It is usually manifested as blood in sputum, hemoptysis is rare.
  • Hemoptysis is the most suggestive symptom of lung cancer.

    • Dyspnea

  • About 10% of lung cancer patients have dyspnea as the first symptom.
  • It manifests as chest tightness, shortness of breath, and some patients may have chest pain.

    • Fever

  • It can be caused by necrosis of tumor tissue or secondary pneumonia (such as obstructive pneumonia).
  • Fever is characterized by delayed and repeated, sometimes good and sometimes bad, difficult to cure.
  • Intermittent moderate or low fever is common, and high fever may be present when combined with infection.

    • Weight loss, malaise

    The tumor may cause consumption, loss of appetite, etc., leading to malaise with weight loss.

    Wheezing

  • It is a harsh sound made when inhaling.
  • If the tumor is located in the large airways, especially in the main bronchial tubes, it can often cause symptoms of restrictive stridor.

    • External Invasion Symptoms

    Superior vena cava obstruction syndrome

  • About 10% of lung cancer patients consult the doctor with this as the first symptom.
  • The main manifestations are edema of the head and neck or even both upper limbs, aneurysm of the veins in the neck and upper chest (the veins are in the form of stripes, clearly visible), capillary dilatation, etc.

    • Horner’s syndrome

    Sunken eyeballs, drooping upper eyelids, small eye fissures, narrow pupils, and absence of facial sweating on the side where lung cancer occurs.

    Apical lung tumor syndrome

    On the basis of Horner’s syndrome, cancer cells further destroy the 1st and 2nd ribs and brachial plexus nerves, causing pain in the upper limbs.

    Hoarseness

  • Involvement of the recurrent laryngeal nerve causes hoarseness.
  • Some lung cancer patients may present to the doctor with this as their first symptom.

    • Difficulty in swallowing

    It is mostly caused by direct invasion of tumor or lymph node metastasis compressing esophagus.

    Pleural effusion

  • Invasion of pleura can cause pleural effusion (hydrothorax), which is often a large amount of bloody effusion.
  • At first, patients gradually feel chest tightness. As the amount of fluid increases, chest pain decreases or disappears, but dyspnea increases.

    • Metastatic symptoms

    Intracranial metastasis

  • May be asymptomatic in the early stages.
  • Central nervous system symptoms are often present:
    • 头痛、呕吐、眩晕。
    复视（双眼同时看同一物体时产生两个影像）。
    共济失调（如动作笨拙、走路不稳）。
    偏瘫（一侧上下肢运动障碍）。
    癫痫发作（俗称“抽风”或“羊痫风”）等。
  • Sometimes accompanied by altered mental status and visual disturbances.

    • Bone metastases

  • Commonly found in the ribs, spine, pelvis and long bones.
  • They may be asymptomatic in the early stages, but may be associated with localized pain and tenderness in the later stages.
  • If the spinal metastasis compresses or invades the spinal cord, it may lead to urinary and fecal incontinence or paraplegia.

    • Liver metastasis

  • Hepatomegaly and pain in the liver area may occur.
  • It may be accompanied by loss of appetite, nausea, emaciation, and elevation of liver enzymes such as aspartate aminotransferase (AST) or bilirubin.

    • Adrenal metastasis

  • May present with symptoms of Addison’s disease, with loss of appetite, diarrhea, deepening of skin color, loss of axillary hair, and low blood pressure.

    • Lymph node metastasis

  • Often metastasize first to hilar lymph nodes along the lymphatic reflux pathway, followed by mediastinal and supraclavicular lymph nodes.
  • The enlarged superficial lymph nodes are usually hard and can be fused into a mass, and are not accompanied by pressure pain.

    • Others

    Lung cancer may metastasize to many parts of the body leading to different clinical signs, such as subcutaneous nodules, skin ulcers and abdominal pain.

    Malignant stasis, also known as malignant fluid, is seen in some advanced cancer patients. It is characterized by extreme emaciation, weakness, general exhaustion and other symptoms.

    Paraneoplastic syndrome

    A few lung cancer patients may have some rare symptoms and signs not caused by direct invasion or metastasis of the tumor, which are called paraneoplastic syndrome or paraneoplastic syndrome.

    Hypertrophic Pulmonary Osteoarthropathy

  • It is mostly seen in patients with lung adenocarcinoma.
  • The main manifestations are pain in large joints, pestle-like fingers/toes (abnormal manifestation of hyperplasia and hypertrophy at the ends of fingers or toes, which are enlarged in the shape of a pestle) and so on.
  • This manifestation may occur in the early stage of lung cancer or precede the localized symptoms of lung cancer, and may even be the only symptom of lung cancer consultation.

    • Cushing’s syndrome

    Ectopic secretion of adrenocorticotropic hormone can cause Cushing’s syndrome.

    Patients usually present with muscle weakness, weight loss, hypertension, hirsutism, and osteoporosis.

    Dermatomyositis and Polymyositis

    Dermatomyositis and polymyositis are 2 different forms of inflammatory myopathies, both of which clinically present with muscle weakness.

    These inflammatory myopathies can be the first symptom of lung cancer or can appear later in the course of lung cancer.

    Hypercalcemia

  • Hypercalcemia in patients with lung cancer may be due to bone metastases and, in a few cases, to tumor-secreted parathyroid hormone-related proteins, osteotriol, or other cytokines, including osteoclast activating factor.
  • Symptoms of hypercalcemia include anorexia, nausea, vomiting, constipation, lethargy, polyuria, irritable thirst, and dehydration.
  • Blurred consciousness and coma as well as renal failure and renal calcinosis are late manifestations.

    • Male breast development

    The main manifestation is bilateral or unilateral breast development.

    Access to medical care

    Medical consultation for lung adenocarcinoma is not significantly different from other types of lung cancer.

    Department of Medicine

    Medical Oncology

    Patients diagnosed with lung adenocarcinoma may choose to undergo drug treatment, such as chemotherapy, targeted therapy and immunotherapy, in the Department of Medical Oncology.

    Thoracic Surgery

    Please consult the Department of Thoracic Surgery if nodules or space-occupying lesions in the lungs are detected by chest imaging (X-rays, chest CT, etc.) during a routine physical examination or other checkups.

    Respiratory Medicine

    When symptoms such as cough, blood in sputum or hemoptysis, wheezing, chest pain, etc. occur, please consult the Department of Respiratory Medicine.

    Preparation for medical treatment

    Preparing for your visit: registering, preparing your documents, FAQs

    Tips for your visit to the doctor

    Chest X-ray or CT examination may be required. Please avoid wearing metal clothing such as shirts with buttons, blouses with sequins, and dresses with zipper openings.

    Preparation Checklist for Medical Treatment

    症状清单

    Pay particular attention to the time of onset of symptoms, special manifestations, etc.

  • Have you been coughing up sputum and for how long?
  • Is there blood in the sputum?
  • Have you had chest tightness and shortness of breath for a long time?
  • Do you have fatigue with unexplained weight loss?
    • 病史清单
  • Do you smoke, how long and how many cigarettes per day?
  • Is there a family history of lung cancer or other malignant tumors?
  • Are there any other diseases, such as tuberculosis?
  • Are there any drug or food allergies?
    • 检查清单

    Test results in the last six months, which can be brought to the doctor’s office

  • Specialized tests: lung biopsy pathology report, chest X-ray or CT report, tumor markers.
  • Laboratory tests: blood test, urine test, stool test, blood biochemistry test.
  • Other tests: magnetic resonance imaging (MRI), PET-CT.

    • Diagnosis

    The diagnosis of lung adenocarcinoma can be divided into qualitative diagnosis and staging diagnosis.

  • Qualitative diagnosis: generally, it is necessary to obtain cytology or histology specimens and then conduct pathological examination, which is the “gold standard” for confirming the diagnosis.
  • Staging diagnosis: with the help of CT, ultrasound, magnetic resonance imaging, bone scanning, PET-CT and other imaging examinations, the clinical stage of the patient can be comprehensively evaluated, so as to preliminarily judge the severity of the patient’s condition and provide the basis for the formulation of subsequent treatment plans.

    • Pathologic examination

    Pathological examination is the “gold standard” for the diagnosis of lung adenocarcinoma, while immunohistochemical examination and molecular biology examination can help to determine the molecular staging of lung adenocarcinoma.

    Cytologic examination

  • The sources of cytology specimens mainly include bronchoscopy, plasmapheresis, fine needle aspiration, sputum and bronchial lavage.
  • According to the morphological characteristics of cytology specimens and the results of immunocytochemistry (ICC) staining, cytology specimens can be accurately diagnosed, typed and the source of cells can be determined.

    • Histologic examination

    Morphology (routine HE staining) and histomorphology clarify small cell lung cancer and non-small cell lung cancer.

    Non-small cell lung cancer requires further clarification of squamous lung cancer and lung adenocarcinoma, and immunohistochemistry is needed to assist the diagnosis when necessary.

  • The vast majority of lung adenocarcinomas are positive for epithelial markers such as AE1/3, CAM5.2, EMA, CEA and CK7.
  • The most commonly used immunohistochemical markers for invasive adenocarcinoma are TTF1 and NapsinA, both of which are positive in lung adenocarcinoma.

    • Special reminder: In the pathology report, the expression of a certain immunohistochemical index (positive) is generally represented by “+”, the more “+”, the higher the degree of expression, which may be more helpful to assist in the diagnosis, and the maximum number of “+” can be 3. “.

  • When the pathologist suspects that the tumor involves the lung membranes, special staining of elastic fibers may be necessary to aid in the diagnosis.

    • Molecular Biology Tests

    Gene mutation testing can determine the molecular typing of the driver genes of lung adenocarcinoma and provide a basis for decision-making for subsequent treatment planning.

    常规检测
  • Molecular biology testing for EGFR, ALK, and ROS1 is recommended routinely for patients with lung adenocarcinoma, regardless of stage at diagnosis.
  • For patients with advanced lung adenocarcinoma, it is recommended to detect genes EGFR, ALK, ROS1, c-MET, BRAFV600E, KRAS, HER-2, RET and NTRK.
    • 耐药监测
  • For EGFR tyrosine kinase inhibitor (EGFR-TKI)-resistant patients, secondary biopsy for secondary resistance EGFR T790M testing is recommended.
  • For patients in whom tissue cannot be obtained, plasma circulating tumor DNA (ctDNA) can be used for EGFR T790M testing.
  • When blood tests are negative, patients should still be advised to undergo tissue testing to clarify EGFR T790M mutation status to guide the choice of third-generation EGFR-TKI therapy.

    • Imaging examination

    Commonly used imaging methods for lung adenocarcinoma include chest X-ray, computed tomography (CT), ultrasound, magnetic resonance imaging (MRI), bone imaging (also known as bone scanning), positron emission tomography (PET) and so on.

    Imaging tests can accurately stage the tumor so that precise treatment can be given.

    X-ray examination

    Frontal and lateral chest radiographs, which cannot provide details such as the extent of tumor invasion and lymph node enlargement, are often used as a general physical examination.

    CT examination

  • It is the most commonly used imaging method for diagnosis, clinical staging and follow-up observation of lung adenocarcinoma.
  • Thoracic and abdominal CT can accurately determine the invasion range of primary tumor, mediastinal lymph node metastasis, and whether there is any tumor metastasis in important abdominal organs (such as adrenal glands, liver, retroperitoneal lymph nodes, etc.).
  • In the absence of contraindications, doctors may recommend enhanced scanning for better diagnosis.

    • MRI

  • It is of significance in identifying microinvasive adenocarcinoma, adenocarcinoma in situ and invasive adenocarcinoma; it is also commonly used to evaluate the efficacy of chemotherapy and targeted drugs.
  • Under special circumstances, it can be used to determine the invasion of chest wall or mediastinum, and to show the relationship between suprapulmonary sulcus tumors and brachial plexus nerves and blood vessels.
  • Enhanced MRI of the brain can be used as a routine examination of lung adenocarcinoma before operation or primary treatment and staging.

    • PET-CT examination

    Whole body PET-CT examination can further improve the accuracy of staging diagnosis of lung adenocarcinoma. However, it is more expensive.

    Bone scan

  • Whole-body bone imaging is a routine test to exclude bone metastasis, with high sensitivity but low specificity.
  • When suspected bone metastatic lesions are found in whole-body bone imaging, it is generally recommended to add MRI examination for clear diagnosis.

    • Ultrasonography

  • Ultrasonography of bilateral cervical and supraclavicular lymph nodes can make up for the insufficiency of physical examination and CT examination in determining lymph node metastasis in this region.
  • Puncture biopsy of lymph nodes suspected of metastasis can be performed, and further pathologic diagnosis can be made.

    • Laboratory examination

  • Serological examination of lung cancer, especially the detection of tumor markers, is helpful for the auxiliary diagnosis of lung cancer, judgment of therapeutic efficacy and follow-up monitoring.
  • Serum carcinoembryonic antigen (CEA) is generally used as the main marker of lung adenocarcinoma, and the serum level is correlated with the degree of infiltration of lung adenocarcinoma and the presence or absence of pleural metastasis, and the higher the level of CEA is, the later the clinical staging is.

    • Staging

    The staging of lung adenocarcinoma follows the staging standard of lung cancer, which is helpful for formulating treatment plan, evaluating therapeutic effect and judging prognosis.

    TNM staging

    Currently, TNM staging of lung cancer is a staging system jointly developed by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC), which is mainly based on the three elements of T, N and M. The TNM staging of lung adenocarcinoma is based on the following three elements

  • T: represents the extent of the primary tumor, mainly referring to the size of the primary tumor foci and the degree of extravasation.
  • N: represents the situation of regional lymph node metastasis, including the number of metastases and regional extent.
  • M: represents the situation of distant metastasis, which mainly means that cancer cells are also present in other organs.

    • Special reminder: TNM will be followed by Arabic numerals, the larger the number, the more serious it is.

    Overall Staging

    According to different TNM staging, the total overall staging (prognostic grouping) of the patient is finally determined, which is indicated by the Roman letters I, II, III and IV.

    Overall staging TNM stagingStage 0 TisN0M0Stage 0TisN0M0Stage IA TisN0M0ⅠA stageT1N0M0ⅠB period T2aN0M0ⅠB periodT2aN0M0ⅡA stage T2bN0M0

    ⅡA stage

    T2bN0M0

    IIB stage T1a~cN1M0T2aN1M0T2bN1M0T3N0M0

  • Phase IIB
  • T1a～cN1M0T2aN1M0T2bN1M0T3N0M0

    • Phase IIIA T1a～cN2M0T2a～bN2M0T3N1M0T4N0M0T4N1M0

    Stage IIIA

  • T1a～cN2M0T2a～bN2M0T3N1M0T4N0M0T4N1M0
  • Phase IIIB T1a～cN3M0T2a～bN3M0T3N2M0T4N2M0

    • Stage IIIB

    全部分期
  • T1a～cN3M0T2a～bN3M0T3N2M0T4N2M0

    • Stage IIICT3N3M0T4N3M0

  • Stage IIIC
    • 肺腺癌的治疗一般采取多学科综合治疗（MDT）与个体化治疗相结合的原则。
    根据患者的身体状况、肿瘤的病理组织学类型和分子分型、侵及范围和发展趋向，采取多学科综合治疗的模式。

    T3N3M0T4N3M0

    Phase IVAAny T, any N, M1a～b

    Stage IVA

    手术治疗

    Any T, any N, M1a～b

  • Phase IVB Any T, any N, M1c
  • Stage IVB

    • Any T, any N, M1c

    术后治疗

    Differential Diagnosis

    Lung adenocarcinoma is the final diagnosis after pathologic confirmation, but it may sometimes be confused with other lung diseases before the diagnosis is confirmed, and a differential is needed.

  • Differentiation of other subtypes of lung cancer
  • Similarities: In pathological examination, when lung adenocarcinoma is poorly differentiated, the histologic features are similar to those of lung low-differentiated squamous carcinoma and sarcomatoid carcinoma.
    • 完全切除的ⅠB期肺腺癌患者，不推荐常规应用术后辅助化疗、放射治疗。
    但有高危险因素者［如低分化肿瘤（包括神经内分泌肿瘤但不包括分化良好的神经内分泌肿瘤）、脉管侵犯、脏层胸膜侵犯、气腔内播散、姑息性切除］推荐进行术后辅助化疗。
    病理亚型以实体型或微乳头为主的ⅠB期腺癌患者也可考虑辅助化疗。
    EGFR突变阳性的患者，可考虑应用奥希替尼辅助治疗。

    Differences: Some poorly differentiated lung adenocarcinomas need immunohistochemical examination to distinguish them from poorly differentiated squamous carcinoma and sarcomatoid carcinoma.

    Differentiation between primary and metastatic

    Although lung adenocarcinoma is the same, metastatic adenocarcinoma may also be formed by thyroid cancer, prostate cancer and gastrointestinal adenocarcinoma that have metastasized to the lung.

    Similarity: Lung tumors are all adenocarcinomas.

    Differences: primary lung cancer and metastatic cancer need to be identified by combining immunohistochemical indexes such as TTF1, NapsinA, TG, PSA, PAP and villin.

    Treatment

    辅助化疗
  • Purpose of treatment
  • Through the planned application of surgery, radiotherapy, chemotherapy, molecular targeted therapy and immunotherapy, with a view to maximizing the survival time, increasing the survival rate, controlling tumor progression and improving the quality of life of patients.
    • 辅助靶向治疗

    Treatment Principles

    辅助免疫治疗

    Stage I

    Stage I lung adenocarcinoma, which can be categorized into Stage IA and Stage IB, is preferred to be resected by radical surgery, and if patients are not suitable for surgery, radiotherapy can be chosen.

    Patients suitable for surgery

  • There are mainly the following surgical treatment options, which need to be determined according to the specific conditions of patients.
  • Anatomic lobectomy + hilar mediastinal lymph node dissection.

    • Anatomic lobectomy + hilar mediastinal lymph node dissection with minimally invasive techniques (thoracoscopic, robot-assisted).

    Reoperation is recommended for stage I patients with positive margins, and postoperative combined radiotherapy is recommended for patients who cannot undergo reoperation for any reason.

    For incomplete surgical resection, such as stage I patients with positive margins, reoperation is generally recommended, and for patients who cannot be reopened for any reason, postoperative combined radiotherapy is recommended.

    If complete surgical resection is achieved, the following follow-up treatment options are available depending on the circumstances:

    N0～1的情况

    Stage IA: Patients with completely resected stage IA lung adenocarcinoma are not recommended to routinely apply postoperative adjuvant chemotherapy, radiotherapy and targeted drug therapy, etc.

  • Stage ⅠB
  • Patients who are not suitable for surgery
    • N2的情况
  • For patients with severe medical comorbidities, advanced age, refusal of surgery and other contraindications to surgery, stereotactic radiotherapy (SBRT/ASBR) can be performed.
    • 手术切除+辅助化疗±术后放疗。
    新辅助化疗±放疗+手术±辅助化疗±术后放疗。
  • Stage II
    • 新辅助化疗±放疗+手术±辅助化疗±术后放疗。
    靶向治疗

    For stage II lung adenocarcinoma, radical surgical resection is preferred, and radical radiotherapy can be chosen if the patient is not suitable for surgery.

    免疫治疗

    Patients suitable for surgery

    The choice of operation is the same as stage I. However, reoperation is recommended for stage II patients with positive margins, and postoperative radiotherapy is recommended for patients who cannot undergo reoperation for any reason.

    定义

    For patients with completely resected stage II lung adenocarcinoma, 4 cycles of postoperative adjuvant chemotherapy with platinum-containing two-drug regimen is recommended.

  • The starting time of adjuvant chemotherapy is recommended when the patient’s physical condition is basically back to normal after surgery, usually 4 to 6 weeks after surgery, and the latest recommendation is not more than 3 months after surgery.
  • Patients with stage II lung adenocarcinoma testing positive for EGFR after surgery can consider applying oxitinib or ectinib for adjuvant treatment after adjuvant chemotherapy.
  • Patients with stage II lung adenocarcinoma testing negative for driver genes after surgery, such as positive PD-L1 expression (≥1%) may be treated with adjuvant atirizumab after platinum-based chemotherapy.
    • 治疗方案
  • Patients who are not suitable for surgery
    • 若患者身体素质较好，如PS 0～1分，则推荐首选治疗为根治性同步化放疗。
    若同步放化疗后无疾病进展，可考虑加用度伐利尤单抗维持治疗。
    同步化疗方案：依托泊苷+顺铂；长春瑞滨+顺铂；培美曲塞+顺铂或卡铂；紫杉醇类+顺铂或卡铂
  • For patients with severe medical comorbidities, advanced age, refusal of surgery and other contraindications to surgery, there are several main treatment options, which need to be tailored to the patient’s specific situation.
    • 若患者无法耐受同步化放疗，序贯放化疗优于单纯放疗。
    序贯化疗方案：长春瑞滨+顺铂；紫杉醇+顺铂或卡铂；培美曲塞+顺铂或卡铂。
    建议行化疗2～4个周期评估后再行放疗。
  • Radiation therapy followed by chemotherapy with a platinum-containing two-drug regimen.

    • Synchronized radiotherapy: three-dimensional conformal radiotherapy or conformal intensity-modulated radiotherapy + chemotherapy.

    Stage III

    Stage III lung adenocarcinoma, including stages IIIA, IIIB and IIIC, is divided into resectable and unresectable categories according to whether the tumor has the possibility of surgical resection.

    Treatment of patients in resectable category

    The resectable category of stage III refers to some stage IIIA and IIIC patients. According to the regional lymph nodes (N), they can be further divided into N0 to 1 and N2 cases.

    免疫药物

    For patients with T3 to 4N1 or T4N0 in stage III, the following treatment options are available:

    PD-L1检测

    Surgery + adjuvant chemotherapy.

  • Neoadjuvant therapy ± radiotherapy + surgery.
  • For N2 stage with a single group of enlarged mediastinal lymph nodes and <3 cm in diameter, or two groups of enlarged mediastinal lymph nodes without fusion and expected to be completely resected, the following treatment options are available:

    • For patients with N2 multisite lymph node metastases who also anticipate possible complete resection, the following treatment options are available:

    EGFR敏感基因突变

    Patients with stage III lung adenocarcinoma, after radical surgery, can be treated with adjuvant therapy with ositinib or ecliptinib after surgery if the pathologic test is positive for EGFR mutation.

  • Patients with stage III lung adenocarcinoma, after radical surgery, if the driver gene is negative. If positive for PD-L1 expression (≥1%) can be treated with adjuvant atirizumab after platinum-based chemotherapy.
  • Treatment of patients in the unresectable category
  • Unresectable stage IIIA, IIIB, and IIIC are mainly defined as having the following imaging or lymph node pathologic evidence.
  • Multiple ipsilateral mediastinal lymph node metastases into a large mass or multiple metastases (IIIA: T1-2N2 or IIIB: T3-4N2).
    • ALK 融合基因阳性

    Contralateral hilar and mediastinal lymph nodes, or ipsilateral and contralateral diagonal or supraclavicular lymph node metastases (IIIB: T1-2N3; IIIC: T3-4N3).

  • The lesion invaded the heart, aorta, and esophagus (IIIA: T4N0-1).
  • Radical synchronized radiotherapy
    • ROS1融合基因阳性

    Sequential radiotherapy

    If the patient’s physical condition is poor, such as PS 0-2 points, radiotherapy alone (3D conformal radiotherapy) or sequential radiotherapy + chemotherapy can be considered.

    其他基因阳性
    Stage IVBefore starting treatment for stage IV lung adenocarcinoma patients, tumor tissues should be obtained for gene mutation testing, such as EGFR, ALK and ROS1, etc., and the corresponding treatment strategy should be decided according to the status of the above driver genes.Driver gene negativeFor patients with negative driver genes, platinum-containing two-drug regimens are the standard first-line chemotherapy regimen, and can be combined with anti-vascular therapy such as bevacizumab or vascular endothelial inhibitory protein on top of chemotherapy.Platinum-containing two-drug chemotherapy based on immune checkpoint inhibitors in combination with pemetrexed is recommended for patients with suitable conditions.

    Commonly used immune checkpoint inhibitors include pembrolizumab, karelizumab, sindilizumab, tirilizumab, atelizumab, and sugilizumab.

    PD-L1 expression testing is generally required when using immune checkpoint inhibitors.

    For patients with positive PD-L1 expression (≥1%), a single agent such as pembrolizumab may be used, but the benefit is more pronounced in patients with high PD-L1 expression (≥50%).

    寡转移

    For patients with high PD-L1 expression (≥ 50%), atelizumab can be used as a single agent.

  • Driver gene positive
  • [Hint] For more, please refer to reading EGFR mutant lung cancer
    • 广泛转移

    EGFR-TKIs are recommended, and ositinib, gefitinib, erlotinib, erlotinib, ectinib, afatinib, and amitinib are available.

    For patients with brain metastasis, ositinib is preferentially recommended.

    Ⅰ期

    For patients with non-classical mutations such as G719X, L861Q, S768I, afatinib is first recommended.

    For patients with EGFR-sensitive gene mutations detected in the course of first-line chemotherapy already started, it is recommended to switch to EGFR-TKIs after completing conventional chemotherapy (including maintenance therapy), or to start targeted therapy after interrupting chemotherapy.

    手术治疗

    For more information, please refer to reading ALK fusion lung cancer

  • You can choose alectinib, ceritinib, enzatinib, crizotinib, buxtitinib.
  • Patients who are found to be positive for ALK fusion gene in the course of chemotherapy already started in the first line, it is recommended that conventional chemotherapy can be completed, including switching to targeted therapy after maintenance therapy or starting targeted therapy after interruption of chemotherapy.

    • For more information, please read ROS1 fusion lung cancer.

    术后治疗

    Crizotinib is recommended, or platinum-containing two-agent chemotherapy or platinum-containing two-agent chemotherapy + bevacizumab.

    Gene-related drugs

  • MET14 Sevortinib
  • MET14
    • 完全切除的ⅠB期肺腺癌患者，不推荐常规应用术后辅助化疗、放射治疗。
    但有高危险因素者［如低分化肿瘤（包括神经内分泌肿瘤但不包括分化良好的神经内分泌肿瘤）、脉管侵犯、脏层胸膜侵犯、气腔内播散、姑息性切除］推荐进行术后辅助化疗。
    病理亚型以实体型或微乳头为主的ⅠB期腺癌患者也可考虑辅助化疗。
    EGFR突变阳性的患者，可考虑应用奥希替尼辅助治疗。

    Sevortinib

    BRAF V600 Darafenib in combination with Trametinib

    Ⅱ期

    BRAF V600

    Darafenib in combination with trametinib

    NTRK entrectinib (Entrectinib) larotrectinib (larotrectinib)

    辅助化疗
  • NTRK
  • Entrectinib (Entrectinib) larotrectinib (larotrectinib)
    • 辅助靶向治疗

    RET Selpercatinib (Selpercatinib)

    辅助免疫治疗

    RET

    Selpercatinib (Selpercatinib)

    Most of the targeted drugs targeting the above genes are not approved for marketing in China or are not approved for indications regarding lung adenocarcinoma, and patients may choose to participate in clinical trials or adopt a driver gene-negative treatment regimen.

  • Treatment of distant metastasis
  • Most patients with stage IV lung adenocarcinoma have distant metastasis, which can be categorized into oligometastasis (only one distant metastatic lesion) and extensive metastasis (two or more distant metastatic lesions at the same time).
    • Ⅲ期

    For patients with oligometastases (only one metastatic lesion), after effective systemic treatment, the use of radiotherapy, surgery and other local therapies can further prolong the survival of patients.

    Brain or adrenal metastases: Aggressive local treatment, including surgical resection of brain or adrenal metastases, or conventional radiotherapy/SBRT for brain or adrenal metastases, combined with systemic therapy as appropriate.

    Bone metastases: receive radiotherapy in combination with bisphosphonates. For patients with weight-bearing bone metastases, surgery to the metastases plus radiotherapy is recommended, combined with systemic therapy as indicated.

    N0～1的情况

    For patients with extensive metastases of lung adenocarcinoma, the treatment of oligometastases is generally referred to and supplemented by palliative treatment, aiming at relieving symptoms, alleviating pain and improving quality of life.

  • Palliative treatment includes taking palliative surgery, chemotherapy, radiotherapy, endocrine therapy, targeted therapy, immunotherapy, as well as other means that can relieve patients’ symptoms, such as pain relief treatment.
  • Stage I lung adenocarcinoma, which can be categorized into Stage IA and Stage IB, is preferred to be resected by radical surgery, and if patients are not suitable for surgery, radiotherapy can be chosen.
    • N2的情况
  • Patients suitable for surgery
    • 手术切除+辅助化疗±术后放疗。
    新辅助化疗±放疗+手术±辅助化疗±术后放疗。
  • There are mainly the following surgical treatment options, which need to be determined according to the specific conditions of patients.
    • 新辅助化疗±放疗+手术±辅助化疗±术后放疗。
    靶向治疗

    Anatomic lobectomy + hilar mediastinal lymph node dissection.

    免疫治疗

    Anatomic lobectomy + hilar mediastinal lymph node dissection with minimally invasive techniques (thoracoscopic, robot-assisted).

    Reoperation is recommended for stage I patients with positive margins, and postoperative combined radiotherapy is recommended for patients who cannot undergo reoperation for any reason.

    定义

    For incomplete surgical resection, such as stage I patients with positive margins, reoperation is generally recommended, and for patients who cannot be reopened for any reason, postoperative combined radiotherapy is recommended.

  • If complete surgical resection is achieved, the following follow-up treatment options are available depending on the circumstances:
  • Stage IA: Patients with completely resected stage IA lung adenocarcinoma are not recommended to routinely apply postoperative adjuvant chemotherapy, radiotherapy and targeted drug therapy, etc.
  • Stage ⅠB
    • 治疗方案
  • Patients who are not suitable for surgery
    • 若患者身体素质较好，如PS 0～1分，则推荐首选治疗为根治性同步化放疗。
    若同步放化疗后无疾病进展，可考虑加用度伐利尤单抗维持治疗。
    同步化疗方案：依托泊苷+顺铂；长春瑞滨+顺铂；培美曲塞+顺铂或卡铂；紫杉醇类+顺铂或卡铂
  • For patients with severe medical comorbidities, advanced age, refusal of surgery and other contraindications to surgery, stereotactic radiotherapy (SBRT/ASBR) can be performed.
    • 若患者无法耐受同步化放疗，序贯放化疗优于单纯放疗。
    序贯化疗方案：长春瑞滨+顺铂；紫杉醇+顺铂或卡铂；培美曲塞+顺铂或卡铂。
    建议行化疗2～4个周期评估后再行放疗。
  • For stage II lung adenocarcinoma, radical surgical resection is preferred, or radical radiotherapy if the patient is not suitable for surgery.
    • Ⅳ期

    Patients suitable for surgery

    The choice of operation is the same as stage I. However, reoperation is recommended for stage II patients with positive margins, and postoperative radiotherapy is recommended for patients who cannot be reopened for any reason.

    For patients with completely resected stage II lung adenocarcinoma, 4 cycles of postoperative adjuvant chemotherapy with platinum-containing two-drug regimen is recommended.

    The starting time of adjuvant chemotherapy is recommended when the patient’s physical condition is basically back to normal after surgery, usually 4 to 6 weeks after surgery, and the latest recommendation is not more than 3 months after surgery.

    免疫药物

    Patients with stage II lung adenocarcinoma testing positive for EGFR after surgery can consider applying oxitinib or ectinib for adjuvant treatment after adjuvant chemotherapy.

    PD-L1检测

    Patients with stage II lung adenocarcinoma testing negative for driver genes after surgery, such as positive PD-L1 expression (≥1%) may be treated with adjuvant atirizumab after platinum-based chemotherapy.

  • Patients who are not suitable for surgery
  • For patients with severe medical comorbidities, advanced age, refusal of surgery and other contraindications to surgery, there are several main treatment options, which need to be tailored to the patient’s specific situation.

    • Radiation therapy followed by chemotherapy with a platinum-containing two-drug regimen.

    EGFR敏感基因突变

    Synchronized radiotherapy: three-dimensional conformal radiotherapy or conformal intensity-modulated radiotherapy + chemotherapy.

  • Stage III lung adenocarcinoma, including stage IIIA, IIIB and IIIC, is divided into resectable and unresectable categories according to whether the tumor has the possibility of surgical resection.
  • Treatment of patients in resectable category
  • The stage III resectable category refers to some stage IIIA and IIIC patients. According to the regional lymph nodes (N), they can be further divided into N0 to 1 and N2 cases.
  • For patients with T3 to 4N1 or T4N0 in stage III, the following treatment options are available:
    • ALK 融合基因阳性

    Surgery + adjuvant chemotherapy.

  • Neoadjuvant therapy ± radiotherapy + surgery.
  • For N2 stage with a single group of enlarged mediastinal lymph nodes and <3 cm in diameter, or two groups of enlarged mediastinal lymph nodes without fusion and expected to be completely resected, the following treatment options are available:
    • ROS1融合基因阳性

    For patients with N2 multisite lymph node metastases who also anticipate possible complete resection, the following treatment options are available:

    Patients with stage III lung adenocarcinoma, after radical surgery, can be treated with adjuvant therapy with ositinib or ecliptinib after surgery if the pathologic test is positive for EGFR mutation.

    其他基因阳性
    Patients with stage III lung adenocarcinoma, after radical surgery, if the driver gene is negative. If positive for PD-L1 expression (≥1%) can be treated with adjuvant atirizumab after platinum-based chemotherapy.Treatment of patients in the unresectable categoryUnresectable stage IIIA, IIIB, and IIIC are mainly defined as having the following imaging or lymph node pathologic evidence.Multiple ipsilateral mediastinal lymph node metastases into a large mass or multiple metastases (IIIA: T1-2N2 or IIIB: T3-4N2).Contralateral hilar and mediastinal lymph nodes, or ipsilateral and contralateral diagonal or supraclavicular lymph node metastases (IIIB: T1-2N3; IIIC: T3-4N3).

    The lesion invaded the heart, aorta, and esophagus (IIIA: T4N0-1).

    Radical synchronized radiotherapy

    Sequential radiotherapy

    寡转移

    If the patient’s physical condition is poor, such as PS 0-2 score, radiotherapy alone (3D conformal radiotherapy) or sequential radiotherapy + chemotherapy can be considered.

  • Before starting treatment, patients with stage IV lung adenocarcinoma should obtain tumor tissues for gene mutation detection, such as EGFR, ALK and ROS1, etc., and decide the corresponding treatment strategy according to the above driver gene status.
  • Driver gene negative
    • 广泛转移

    For patients with negative driver genes, platinum-containing two-drug regimens are the standard first-line chemotherapy regimen, and can be combined with anti-vascular therapy such as bevacizumab or vascular endothelial inhibitory protein on top of chemotherapy.

    Platinum-containing two-drug chemotherapy based on immune checkpoint inhibitors in combination with pemetrexed is recommended for patients with suitable conditions.

    Commonly used immune checkpoint inhibitors include pembrolizumab, karelizumab, sindilizumab, tirilizumab, atelizumab, and sugilizumab.

    PD-L1 expression testing is generally required when using immune checkpoint inhibitors.

    For patients with positive PD-L1 expression (≥1%), a single agent such as pembrolizumab may be used, but the benefit is more pronounced in patients with high PD-L1 expression (≥50%).

    For patients with high PD-L1 expression (≥ 50%), atelizumab can be used as a single agent.

    Driver gene positive

    [Hint] For more, please refer to reading EGFR mutant lung cancer

    EGFR-TKIs are recommended, and ositinib, gefitinib, erlotinib, erlotinib, ectinib, afatinib, and amitinib are available.For patients with brain metastasis, ositinib is preferentially recommended.For patients with non-classical mutations such as G719X, L861Q, S768I, afatinib is first recommended.For patients with EGFR-sensitive gene mutations detected in the course of first-line chemotherapy already started, it is recommended to switch to EGFR-TKIs after completing conventional chemotherapy (including maintenance therapy), or to start targeted therapy after interrupting chemotherapy.For more information, please refer to reading ALK fusion lung cancer

    You can choose alectinib, ceritinib, enzatinib, crizotinib, buxtitinib.

    Patients who are found to be positive for ALK fusion gene in the course of chemotherapy already started in the first line, it is recommended that conventional chemotherapy can be completed, including switching to targeted therapy after maintenance therapy or starting targeted therapy after interruption of chemotherapy.

    EGFR突变

    For more information, please read ROS1 fusion lung cancer.

    ALK融合

    Crizotinib is recommended, or platinum-containing two-agent chemotherapy or platinum-containing two-agent chemotherapy + bevacizumab.

    Gene-related drugs

    ROS1融合

    MET14 Sevortinib

    MET14

  • Sevortinib
  • BRAF V600 Darafenib in combination with Trametinib
  • BRAF V600

    • Darafenib in combination with trametinib

    NTRK entrectinib (Entrectinib) larotrectinib (larotrectinib)

    NTRK

  • Entrectinib (Entrectinib) larotrectinib (larotrectinib)
  • RET Selpercatinib (Selpercatinib)
  • RET
  • Selpercatinib (Selpercatinib)
  • Most of the targeted drugs targeting the above genes are not approved for marketing in China or are not approved for indications regarding lung adenocarcinoma, and patients may choose to participate in clinical trials or adopt a driver gene-negative treatment regimen.

    • Treatment of distant metastasis

    Most patients with stage IV lung adenocarcinoma have distant metastasis, which can be categorized into oligometastasis (only one distant metastatic lesion) and extensive metastasis (two or more distant metastatic lesions at the same time).

    For patients with oligometastases (only one metastatic lesion), after effective systemic treatment, the use of radiotherapy, surgery and other local therapies can further prolong the survival of patients.

  • Brain or adrenal metastases: Aggressive local treatment, including surgical resection of brain or adrenal metastases, or conventional radiotherapy/SBRT for brain or adrenal metastases, combined with systemic therapy as appropriate.
  • Bone metastases: receive radiotherapy in combination with bisphosphonates. For patients with weight-bearing bone metastases, surgery to the metastases plus radiotherapy is recommended, combined with systemic therapy as indicated.

    • For patients with extensive metastases of lung adenocarcinoma, the treatment of oligometastases is generally referred to and supplemented by palliative treatment, aiming at relieving symptoms, alleviating pain and improving quality of life.

    Palliative treatment includes taking palliative surgery, chemotherapy, radiotherapy, endocrine therapy, targeted therapy, immunotherapy, and other means that can relieve patients’ symptoms, such as pain relief treatment.

    Prognosis

    Survival

  • Survival of patients with lung adenocarcinoma depends largely on the TNM stage of the tumor at the time of disease detection.
  • Survival varies significantly among patients with different clinical stages. There is no authoritative information on survival studies for lung adenocarcinoma, which can be roughly assessed from data on non-small cell lung cancer.
  • 5-Year Survival Rates by Stage
  • According to a study that comprehensively analyzed several large-scale statistical results from 2000 to 2012, the 5-year survival rates of non-small cell lung cancer by stages in China are as follows:
  • Stage 5-year survival rate

    • Stage I 75%

    早期下床活动

    Stage I

  • 75%
  • Stage II 55%
  • Stage II
  • 55%
  • Stage III 20
    • 手臂和肩关节的运动

    Stage III

  • 20%
  • Stage IV 5%
  • Stage IV
    • 肺功能锻炼
  • 5%
  • Survival rate of driver gene positive

    • Overall, treated patients with driver gene-positive lung cancer showed significant improvement in overall survival, and with the availability of related drugs, patients may achieve even longer survival.

  • Several studies have shown that for patients with brain metastases from lung adenocarcinoma in EGFR-mutant lung cancer, the time to intracranial disease control after aggressive treatment ranged from 12.5 to 22.6 months, and the survival time ranged from 15.1 to 41.1 months.
  • ALK fusion positivity occurs most often in lung adenocarcinoma, and therefore the survival of ALK fusion patients with lung adenocarcinoma can be roughly predicted from the data of ALK fusion lung cancer patients.
  • Several studies have shown that the median overall survival (mOS) of patients with ALK fusion lung cancer can be up to 89 months.

    • One study showed that patients with ROS1-fusion lung cancer had a median overall survival (mOS) of 51.4 months, with 1- and 4-year survival rates of 79% and 51%, respectively.

    Special reminder.

  • The overall survival time of cancer patients can be roughly predicted by the 5-year survival rate, which refers to the proportion of patients whose tumors survive for more than 5 years after various comprehensive treatments. the probability of recurrence after 5 years is low, and it is generally regarded as a clinical cure.
  • Median Overall Survival (mOS) can also be referred to as “half overall survival” and indicates that 50% of individuals will live beyond this time. For example, if 1,000 people are enrolled in a clinical trial, and each individual’s survival time is ranked from smallest to largest, the 501st individual’s survival time in months indicates the median survival period for the clinical trial.
  • Statistics such as 5-year survival rate and median overall survival are for clinical studies only and do not represent an individual’s specific survival; a patient’s individual survival will need to be determined by a combination of factors, and consultation with the attending physician is recommended.
  • Prognostic factors
  • Prognostic factors are factors that have an impact on the overall survival and quality of life of the patient.
  • These factors mainly include the degree of malignancy of the tumor, the stage of the tumor, lymph node metastasis, treatment, and individual physical condition.

    • Patients with low tumor malignancy have a better prognosis than those with high tumor malignancy.

    In tumor staging, patients belonging to the early clinical stage have a better prognosis than those in the middle or late clinical stage.

  • Patients with no lymph node metastasis have a better prognosis than those with lymph node metastasis.
  • Patients with early regular treatment have better prognosis than those with late treatment; patients with good treatment effect have better prognosis than those with poor treatment effect.
  • Patients with good personal health have a better prognosis than those with poor health.

    • Recurrence and metastasis

    Recurrence of lung cancer refers to the reappearance of tumor after lung cancer surgery.

  • Lung adenocarcinoma is one of the common types of non-small cell lung cancer, so the recurrence or metastasis data of non-small cell lung cancer can be used to roughly assess the recurrence or metastasis of lung adenocarcinoma.
  • Stage I and II non-small cell lung cancer: the recurrence rate of lung cancer about 5 years after surgery is about 30%.

    • Stage III non-small cell lung cancer: the recurrence rate of lung cancer or metastasis about 5 years after surgery is about 60%.

    Daily

    The daily routine of lung adenocarcinoma is not significantly different from that of other types of lung cancer. After treatment such as surgery, radiotherapy or chemotherapy, it does not mean that one can let down his/her guard, and active and strict daily management can help patients to better overcome cancer.

    Daily Management

    Mindset and emotional adjustment

    A good mood and mindset cannot be replaced by drugs.

    After diagnosis, patients may develop a sense of fear and may be afraid of pain, abandonment and death. With the encouragement and help from doctors, family and friends, patients need to get rid of their fear as soon as possible, face the disease squarely, actively follow the medical advice and have an optimistic attitude towards the prognosis.

  • Family members should pay attention to listening to the patient’s heart, improve the patient’s psychological tolerance, and relieve anxiety symptoms.
  • It is recommended that the patient’s family give support so that the patient can face the surgery and other treatments positively with a good mindset.
  • During the period between treatments and after treatment, family members are advised to encourage the patient to do work and household chores as much as possible, so as to reintegrate into social roles.
  • Postoperative activities
  • The purpose is to prevent pulmonary atelectasis, improve respiratory and circulatory function, improve appetite and invigorate the spirit. According to the patient’s tolerance level, encourage early postoperative activities.
  • After awake from anesthesia, encourage patients to move in bed, such as active movement of limbs, hip lifting and intermittent turning.

    • On the first postoperative day, after the vital signs are stable, encourage and assist the patient to sit up in bed, sit on the edge of the bed with legs down or stand and move around the bedside.

    On the second postoperative day, the patient can be helped to walk around the bed for 3 to 5 minutes, and then gradually increase the amount of activity according to the patient’s condition.

    高危人群

    During the activity period, the patient’s drainage tube should be properly protected and the patient’s condition should be closely observed. When symptoms such as dizziness, shortness of breath, tachycardia, palpitations and sweating occur, stop the activity immediately.

  • Patients of advanced age (>70 years old), coronary heart disease and hypertension should not get out of bed early to avoid cardiopulmonary complications due to lack of oxygen. Specific activities should be carried out under the guidance of the physician.
  • The purpose is to prevent adhesion of chest wall muscles on the operated side, shoulder joint stiffness and disuse atrophy.
  • After the patient is awake, he can be assisted to perform lifting exercises of the shoulder joint and arm on the operative side.
  • On the first postoperative day, active shoulder and arm movements, such as arm lifting on the operated side, wall climbing, and shoulder rotation anterior and posterior movements, were started to gradually restore the range of motion of the shoulder joint to the preoperative level and to prevent shoulder ptosis.
  • After total pneumonectomy, the patient is encouraged to take an upright functional position to restore normal posture and prevent scoliosis deformity.

    • Clinically, the method of blowing up balloons is commonly used to exercise lung function, but it needs to be gradual and not overly forceful.

    This method helps to open the closed small airways, expel the residual gas in the lungs, improve pulmonary reopening, and also helps the residual fluid in the chest cavity to be discharged from the drainage tubes after the operation, so as to prevent the occurrence of liquid pneumothorax.

    筛查方法

    Postoperative diet

    When the patient’s consciousness is restored and there is no nausea, water can be started after removing the tracheal tube.

    筛查频率
  • After the recovery of intestinal peristalsis (e.g., exhaustion), the patient can start to eat a light liquid or semi-liquid diet. If the patient does not have any discomfort after eating, it can be changed to a general diet.
  • The diet should be high in protein, high in calories, rich in vitamins and easy to digest, such as fish, steamed eggs, milk, fresh fruits, etc., to ensure nutrition, improve autoimmunity and promote wound healing.
    • 参考文献
    [1]
    中华人民共和国国家卫生健康委员会.原发性肺癌诊疗指南（2022年版）.
    [2]
    中国临床肿瘤学会（CSCO）. 非小细胞肺癌诊疗指南2022[M]. 北京：人民卫生出版社，2022.
    [3]
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