Lung Adenocarcinoma – Non-Small Cell Lung Cancer (NSCLC)

Medically reviewed: 1, February 2024

Lung Adenocarcinoma Non-Small Cell Lung Cancer (NSCLC): introduction

Lung adenocarcinoma, or glandular lung cancer, is a malignant tumor that develops from the glandular epithelium of the bronchial wall. It is the most common type of non-small cell lung cancer.

Among all malignant lung tumors, adenocarcinoma is diagnosed in approximately 40% of cases. Like other forms of lung cancer, it is more common in men than women. It is extremely rare to occur at a young age (practically not detected until the age of 20), the average age of patients is 65-70 years. Despite the fact that the main provoking factor for any lung cancer is smoking, adenocarcinoma is the most common variant of this pathology in non-smokers, as well as in patients under 45 years of age.

Lung adenocarcinoma is characterized by an asymptomatic course in the early stages or nonspecific symptoms, to which patients do not pay due attention. Therefore, the disease is often diagnosed in an advanced state, which reduces the effectiveness of treatment and reduces the chances of long-term survival.

Causes and risk factors

The exact reasons for the development of this oncopathology have not been identified. Active and passive smoking is considered to be the main risk factor. The risk of adenocarcinoma is higher in those who started smoking early, have a long history of smoking, and smoke more than 1 pack of cigarettes per day.

Other risk factors include:

• Prolonged contact with harmful substances in the air. This may be living in an area with an unfavorable environmental situation (high air pollution, emissions from industrial enterprises), occupational hazards (inhalation of asbestos, coal dust, pesticides, certain chemical compounds).
• Hereditary predisposition. If blood relatives in the direct line have been diagnosed with lung adenocarcinoma, the patient should be wary in this regard.
• Chronic lung diseases, especially those resulting in the development of pneumofibrosis – tuberculosis, COPD, calcification.

Nonspecific risk factors that worsen the condition of the body as a whole are poor nutrition with insufficient vitamins, and immunosuppressive conditions.

Symptoms of lung adenocarcinoma

In the early stages of development, the disease does not manifest itself with clear symptoms. Patients may feel weakness, fatigue, a feeling of heaviness, and slight chest pain. As a rule, these symptoms are not associated not only with lung cancer, but also with any serious pathology of this organ; patients often self-medicate and do not consult a doctor. In this regard, most cases of lung adenocarcinoma are detected at late stages.

As the disease progresses, the following symptoms may appear:

• shortness of breath on exertion and at rest;
• cough – dry or with mucous sputum;
• more intense pain syndrome.

In the later stages, when the tumor acquires significant size, the vessels and nearby organs (esophagus, vocal cords) grow, severe symptoms appear:

• difficulty breathing, up to respiratory failure;
• hemoptysis, pulmonary hemorrhage;
• dysphagia – choking, difficulty swallowing;
• hoarseness or loss of voice;
• cardiac dysfunction due to fluid accumulation in the heart sac.

At the same time, the patient’s general well-being deteriorates significantly. The patient loses weight, to the point of exhaustion, he experiences nausea and vomiting, leading to dehydration, severe thirst, constipation, and symptoms of intoxication. When distant metastases appear, signs of damage to the corresponding organs or tissues appear.

Lung adenocarcinoma is often accompanied by paraneoplastic syndrome – a complex of clinical and laboratory manifestations that arise as a result of a nonspecific reaction of the body and the release of biologically active compounds by the tumor. Paraneoplastic syndrome is distinguished by various manifestations – skin rashes, dysfunction of various organs and systems, hormonal imbalances, etc.

You should consult a doctor as soon as possible – in case of a lingering cough, a cold that does not cure for a long time, or a periodic increase in body temperature to low-grade levels (37.5 °C and above). The appearance of blood in the sputum when coughing is a reason to urgently seek medical help.

Classification of lung adenocarcinoma

According to the prevalence of the process:

1. Preinvasive – a single formation with a diameter of up to 3 cm, with a creeping type of growth. There is no germination into the lung stroma, pleura, or blood vessels.
2. Minimally invasive lung adenocarcinoma – characterized by growth into the stroma to a depth of no more than 5 mm. The diameter of the tumor, as in the previous case, is no more than 3 cm. There is no germination into the pleura or blood vessels.
3. Invasive – a neoplasm more than 3 cm in diameter, with invasion into the stroma to a depth of more than 0.5 mm. The tumor invades the blood vessels and pleura, and tumor necrosis is present.

Depending on the presence of the mucous component:

• mucinous adenocarcinoma of the lung;
• non-mucinous.

Nonmucinous (non-mucus producing) lung adenocarcinoma is divided into groups G1, G2 and G3, each of which has specific growth patterns:

• G1 – creeping;
• G2 – acinar, papillary;
• G3 – cribriform, solid, micropapillary, complex glands.

According to the degree of cell differentiation:

• poorly differentiated;
• moderately differentiated;
• well-differentiated adenocarcinoma.

A separate type of lung adenocarcinoma is bronchoalveolar cancer. It, in turn, is divided into the following forms:

• nodal;
• pneumonia-like;
• disseminated.

Atypical forms of lung adenocarcinoma:

• colloidal;
• fetal;
• intestinal type.

Stages of lung adenocarcinoma

To stage this type of lung cancer, the TNM classification is used, where T is the assessment of the primary tumor, N is the assessment of lymph node involvement, M is distant metastases.

Stage classification according to T criteria

Criterion	Signs	Tx
it is impossible to evaluate the primary tumor or the formation is not determined by bronchoscopy, but is verified by the presence of atypical cells in sputum or washings	T0
no primary tumor found	Tis
carcinoma in situ	T1
neoplasm up to 3 cm in diameter or less in greatest dimension, surrounded by pulmonary parenchyma or visceral pleura; There are no signs of invasion proximal to the lobar bronchus during bronchoscopy (the tumor is not localized in the main bronchus)	T1a (mi)	minimal tumor invasion
adenocarcinoma up to 1 cm in diameter in greatest dimension	T1b	tumor 1 to 2 cm in diameter in greatest dimension
neoplasm 2 to 3 cm in diameter in greatest dimension	T1c
adenocarcinoma 3 to 5 cm in diameter in greatest dimension, or: with involvement of the main bronchus, regardless of the distance to the carina (cartilage at the tracheal bifurcation), but without its involvement; with damage to the visceral pleura; with atelectasis or obstructive pneumonitis developing in the hilar regions involving part or all of the lung.	T2
a tumor 3 to 4 cm in diameter in its greatest dimension, or the size of the tumor cannot be determined (for example, when it is inseparable from atelectasis)	T2a	adenocarcinoma 4 to 5 cm in diameter in greatest dimension
tumor 5 to 7 cm in diameter in greatest dimension, or direct invasion of: chest wall (including parietal pleura and superior sulcus tumors); phrenic nerve; parietal pericardium. or metastatic tumor nodes or a node in a pathologically changed lobe are determined	T3
a tumor greater than 7 cm in diameter in greatest dimension, or a lesion: diaphragms; mediastinum; hearts; large vessels; trachea; recurrent laryngeal nerve; esophagus; vertebral body; tracheal bifurcations; visceral pericardium. or there are metastatic node(s) in other ipsilateral lobes	T4

Adenocarcinoma stage classification according to N criteria

Criterion	Signs
it is impossible to assess the condition of regional lymph nodes no metastases to regional lymph nodes	Nx   N0
metastases in the ipsilateral peribronchial and/or ipsilateral root nodes; or metastases in intrapulmonary lymph nodes, including direct involvement of lymph nodes	N1
lymph nodes of one of the lymphatic collectors listed in the signs of criterion N1 are affected	N1a
lymph nodes of several of the lymphatic collectors listed in the signs of criterion N1 are affected	N1b
metastases in ipsilateral mediastinal and/or subcarinal lymph nodes	N2
lymph nodes of one N2 collector are affected without involvement of lymph nodes of the N1 collector (skip metastasis)	N2a1
l/nodes of one collector N2 are affected with involvement of l/nodes of the collector N1	N2a2
multiple involvement of collector lymph nodes N2	N2b
metastases in the contralateral mediastinal, hilar, any scalene or supraclavicular lymph nodes	N3

Adenocarcinoma stage classification according to M criteria

Criterion	Signs
no distant metastases	M0
distant metastases are present	M1
tumor nodules in the contralateral lung, tumor nodules of the pleura, metastatic pleural or pericardial effusion	M1a
single distant tumor node	M1b
multiple extrapulmonary metastases in one or more organs	M1c

Diagnostics of lung adenocarcinoma

Clinical, laboratory and instrumental methods are used to diagnose this type of cancer.

Clinical diagnostic methods

When interviewing the patient, the doctor finds out the history of life (cases of lung cancer in relatives, smoking history and intensity) and disease (complaints, duration of the disease, the presence of concomitant pathologies of the bronchopulmonary system).

During the examination, the doctor performs:

• auscultation – listening to the lungs with a phonendoscope,
• percussion – determining the boundaries of the lungs by tapping with fingers,

and also:

• pays attention to the color of the patient’s skin,
• evaluates the presence of yellowness of the mucous membranes,
• and the condition of the lymph nodes.

Laboratory diagnostics methods

Laboratory techniques include:

• general blood and urine analysis;
• blood biochemistry;
• microscopic and histological examination of tumor samples or swabs taken during bronchoscopy;
• blood test for tumor markers.

Instrumental diagnostics

Radiation research methods – radiography, CT, MSCT, PET-CT, ultrasound are used in the primary diagnosis of lung adenocarcinoma, to clarify the diagnosis, determine the size of the tumor, and its growth in the tissue. Ultrasound, CT, PET-CT of lymph nodes and various organs are used to assess the condition of regional lymph nodes and the presence of distant metastases.

Bronchoscopy is an endoscopic examination of the trachea and bronchi. Allows you to assess the condition of their mucosa, take a tissue sample for histological examination, and wash away from the surface of small bronchi that are inaccessible to the endoscope.

Thoracoscopy is an endoscopic examination in which an endoscope is passed into the pleural cavity through small incisions in the chest area.

Biopsy – collection of material for subsequent histological or molecular genetic research. Performed during bronchoscopy or thoracoscopy.

Treatment of lung adenocarcinoma

If the disease was detected at an early stage, surgical treatment is preferred. Today, this is the only method that allows radical treatment. The extent of the operation depends on the extent of the tumor process and may include:

• Segmentectomy – removal of a segment of the lung.
• Lobectomy – removal of a lobe of the lung.

Pulmonectomy (removal of one entire lung) is usually indicated for patients with advanced disease. Additionally, during the operation, nearby lymph nodes are removed (lymph node dissection) in order to reduce the likelihood of relapse of the disease. Simultaneously with surgical treatment, or if it is impossible to perform it, methods such as chemotherapy (cisplatin, novelbin) and external beam radiation therapy can be used.

Chemotherapy can be prescribed to patients at stages 2–4 of the disease. The most effective is a combination of several drugs (etopozoid + cisplatin, paclitaxel + carboplatin, etc.). For each stage, the optimal combination of drugs, dosage regimens and number of courses are selected. When combined with surgical treatment, chemotherapy can improve disease-free and five-year survival rates.

Radiation therapy is usually used in late stages of the disease as symptomatic relief.

The current treatment option for lung adenocarcinoma is targeted therapy. The target for such drugs is a specific genetic defect that exists in tumor cells. Thus, for mutations in the EGFR gene, gefitinib, afatinib, and erlotinib are prescribed. For defects in the ALK and ROS1 genes, crizotinib is prescribed.

If the corresponding mutation is not detected during the examination, then the treatment will be ineffective.

In some cases, immunotherapy may be used. The principle of the method is to activate immune mechanisms, which usually do not perceive cancer cells as foreign and do not attack them. Nowadays, this type of treatment is being actively studied and developed, modern drugs are appearing that show good results and are accompanied by a minimum of side effects.

Treatment on different stages

Treatment tactics depend on the stage of the malignant neoplasm. For lung adenocarcinoma in situ, they are sometimes limited to radical removal of the tumor with excision of a small part of the lung – wedge resection, or segmentectomy. If the tumor is minimally invasive and there is a high risk of recurrence, chemotherapy is prescribed in addition to surgical treatment.

Lung adenocarcinoma treatment on stage 1 and 2

At stages I-II, the resection area is larger; depending on the size of the tumor, either one or multiple lobes of the lung may be surgically removed, a procedure known as lobectomy. Alternatively, in more severe cases, the entire lung may need to be eliminated, a process called pneumonectomy. If the spread of the process to the lymph nodes is suspected, lymph node dissection is performed. After surgery, adjuvant chemotherapy is indicated.

Lung adenocarcinoma treatment on stage 3

For stage III lung adenocarcinoma, surgical treatment is not always possible. If the operation is still carried out, they try to remove as much of the affected tissue as possible. In most cases, lymph node removal is also performed. In the postoperative period, adjuvant chemotherapy is performed to destroy potentially remaining malignant cells.

Lung adenocarcinoma treatment on stage 4

Stage IV is almost always inoperable. To treat lung adenocarcinoma at this stage, chemotherapy, radiation therapy and modern methods – targeted and immunotherapy – are used. Targeted therapy drugs act on specific mutations in tumor cells, previously identified using molecular genetic analysis. Immunotherapy is the activation of the body’s immune mechanisms to fight tumor cells.

In later stages, patients are given palliative treatment if necessary – painkillers, antiemetics, parenteral nutrition, and other symptomatic therapy.

Lung adenocarcinoma survival rate

When lung adenocarcinoma is detected at pre-invasive and minimally invasive stages and treated adequately, the prognosis is favorable, the five-year survival rate reaches 100%.

The later the disease is detected and treatment is started, the worse the prognosis. At stages I-II, subject to timely treatment, the five-year survival rate is 60-80%. When lung adenocarcinoma is detected at stage 4, the prognosis is unfavorable – without proper treatment, about 90% of patients die within a year.

Unfavorable prognostic factors include the presence of lymph node involvement and the occurrence of distant metastases. Additionally, the survival prognosis is influenced by the patient’s age, general condition, and the presence of concomitant diseases.

Without proper treatment, almost 90% of patients with stage IV die in the first two years. However, if the disease is detected at stages I–II, then the five-year survival rate is 60–80%, which is considered a good indicator for non-small cell lung cancer.