Lung cancer is one of the fastest growing malignancies in terms of incidence and mortality, and one of the most threatening to the health and lives of the population. The following are the risk factors, pathogenesis, pathological manifestations, clinical manifestations, diagnosis and evaluation, treatment and prognosis and prevention of lung cancer.
I. Risk factors
Smoking is the cause of 80%-90% of lung cancers, and secondhand smoke is also an important risk factor. Most risk factors are dose- and time-related, and many carcinogenic factors have synergistic effects with tobacco, for example, tobacco exposure and arsenic in drinking water are associated with lung cancer. Radon is a naturally occurring radioactive gas that is prevalent in homes and causes an estimated 21,000 cases of lung cancer. Lung cancer risk can be assessed by tools.
II. Pathogenesis
A variety of endogenous factors and exposure to environmental carcinogens can lead to lung cancer. Precancerous damage such as adenocarcinoma in situ and microinvasive adenocarcinoma show a progressive course of lung cancer. Familial and genetic alterations also contribute to lung cancer predisposition, which is not spared even in non-smokers. Many intratumoral genetic mutations have been identified, such as EGFR gene mutations in 20% of lung adenocarcinomas, and targeted therapies may be effective in patients with EGFR mutations, such as EGFR inhibitors (erlotinib or afatinib) or monoclonal antibodies (cetuximab). Tumor mutations may also be predictive of treatment response or certain chemotherapy toxicity, which requires further study.
III. Pathology
Lung cancer is divided by histology into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC), which is subdivided into adenocarcinoma, squamous carcinoma, and large cell carcinoma. NSCLC is sometimes poorly differentiated and can only be distinguished by immunohistochemical staining and molecular testing, making diagnosis problematic when the amount of tissue examined is small, and optimal treatment relies on tumor phenotype and genetic features.
IV. Clinical manifestations
Patients with lung cancer may present with symptoms caused by either the primary tumor (e.g. cough, hemoptysis) or intra-thoracic dissemination of the tumor (e.g. Horner syndrome, superior vena cava obstruction syndrome), or distant metastases (e.g. bone pain). Other symptoms are caused by paraneoplastic syndromes. Mortar and pestle finger is the most common paraneoplastic syndrome, the mechanism of which is unclear and is common in NSCLC patients. Other symptoms associated with lung cancer include loss of appetite, weight loss, fatigue, dyspnea, chest or rib pain, and persistent cough. Patients rarely have only one symptom, but often have multiple symptoms together. For example, if a patient has both hemoptysis and weight loss, the chance of developing lung cancer is 9.2%, and people over 40 years old with lung cancer predisposing factors and lung cancer symptoms should be on high alert.
V. Initial evaluation
Initial evaluation of patients suspected of lung cancer includes medical history, physical examination, complete blood count, alkaline phosphatase test, liver transaminases and blood calcium, biochemical indicators (electrolytes, blood urea nitrogen and creatinine), and chest imaging. Normal chest imaging does not exclude lung cancer, as small tumors can be hidden in the mediastinum or other locations in the chest. If lung cancer is still highly suspected, enhanced CT and, if necessary, PET should be performed.
A multidisciplinary team of physicians, including respiratory, oncology, radiology, pathology, radiotherapy and thoracic surgery, should collaborate in the evaluation. The patient’s family physician should be involved in the treatment, especially in the end-stage treatment of the patient.
Diagnostic evaluation
Diagnostic evaluation includes three concurrent steps: tissue diagnosis, staging and functional assessment.
1. Tissue diagnosis
Experienced physicians can determine the type of lung cancer based on clinical presentation and imaging, but sufficient histological biopsies must be performed to clarify the diagnosis and decide on targeted treatment options. The choice of the method to obtain the specimen should be based on tumor type, location, size, patient comorbidities, and the presence of metastasis.
The least invasive method is usually preferred, but if a less invasive method fails to obtain a specimen, a more invasive method should be used. Conventional bronchoscopy is best for obtaining specimens from central damage, whereas CT-guided transthoracic fine needle aspiration is primarily used for peripheral damage. Endotracheal ultrasound and electromagnetic guidance are newer techniques that can increase the success rate of bronchoscopy and are mainly indicated for mediastinal and peripheral damage.
2.Staging
Clinical staging is based on pre-treatment examinations, including CT and PET findings and mediastinoscopic findings. Pathological staging is based on the results of surgical resection, which may lead to an upward or downward revision of clinical staging. For SCLC, the American College of Chest Physicians guidelines recommend the 7th edition TNM staging system, but some physicians still use the simple Veterans Lung Cancer Study Group dichotomous approach to staging SCLC. Limited stage SCLC is defined as cancer confined to a single tolerable radiotherapy area, and extensive stage is defined as cancer beyond a single hemithorax.
3.Functional reserve
Patients with old age, poor nutritional status, and multiple comorbidities may not be able to tolerate pneumonectomy, radiotherapy, and chemotherapy, and treatment should be fully individualized at this time.
The score allows a simple assessment of whether the patient can tolerate chemotherapy well.
0: Adequate physical strength, able to perform pre-morbid physical activities without any restriction
1: limited physical activity, but able to perform light or seated work
2: able to walk and take care of himself/herself, but unable to perform daily tasks for more than half of the day
3: Limited self-care, confined to bed or sitting for more than half of the day
4: unable to care for themselves at all, confined to bed or sitting
5: Death
Patients proposed for lung resection undergo a standardized preoperative evaluation, perform pulmonary function tests, and carbon monoxide diffusion function tests to assess postoperative lung function. The standardized preoperative evaluation also includes brain MRI (except for patients with stage IA NSCLC).
VII. Treatment
1. Non-small cell lung cancer
The treatment of stage I or II NSCLC is minimally invasive if surgery is feasible. stage III invasive NSCLC is aimed at resection of intrathoracic cancer in combination with radiotherapy to reduce the potential for intrathoracic and systemic metastases. patients with stage IV NSCLC or other stages with co-morbidities, or if the patient does not consent, palliative care should be started as early as possible. Early initiation of palliative care can significantly improve the quality of life, reduce the incidence of depression and partially prolong patient survival.
2.Small cell lung cancer
The 5-year survival rate of patients with limited-stage SCLC can reach 25% after treatment. The 5-year survival rate for extensive stage SCLC is 0. Both limited and extensive stage SCLC should be treated with appropriate combination of platinum-containing chemotherapy.
VIII. Prognosis
If the symptoms at the time of presentation are caused by the primary tumor and not by distant metastases or paraneoplastic syndromes, patients usually have a better prognosis; the 5-year survival rate can exceed 50% for limited-stage SCLC and less than 5% for patients with distant metastases. The prognosis of early stage cancer is also better.
IX. Screening
The USPSTF supports annual low-dose spiral CT for people aged 55-80 years with a 30-year smoking history who are still smoking or have quit smoking less than 15 years ago. The American Academy of Family Physicians, however, believes that the available evidence neither supports nor opposes low-dose spiral CT for lung cancer. Therefore, physicians should educate patients, fully inform them of the benefits and possible risks of screening, and then make a shared decision about whether to screen.
X. Prevention
The USPSTF recommends that all smokers be screened for lung cancer, and that smokers be encouraged to quit at each patient visit; physician recommendations are effective in changing patients’ willingness to smoke. Legislation such as banning smoking in public places, banning the sale of tobacco to youth, and charging heavy taxes on tobacco are also effective ways to control tobacco use.