Lung adenocarcinoma is the most common histological type of non-small cell lung cancer, originating from glandular epithelial cells lining the mucous membranes of the bronchi and alveoli. Due to its origin, this disease is also referred to as glandular lung cancer. The primary danger of adenocarcinoma lies in its frequent diagnosis at advanced stages, making effective treatment challenging.

The prevalence of cancer continues to grow. In 2020, 2.2 million people worldwide were diagnosed with this condition. Lung cancer remains the leading cause of cancer-related deaths, claiming nearly 2 million lives annually, according to WHO data.

In the 19th–20th centuries, when tobacco smoking was more widespread, squamous cell lung cancer, particularly among men, was more common. As public awareness increased and governments and health organizations adopted active anti-smoking measures, the situation shifted. Today, adenocarcinoma is the most prevalent form of lung cancer, accounting for about 40% of all lung cancer cases. Among smokers, adenocarcinoma occurs in 65% of cases, while in non-smokers, the figure is 93%.

Is adenocarcinoma small cell lung cancer?

No, adenocarcinoma is not small cell lung cancer – they are two distinct types of lung cancer:

Adenocarcinoma is a type of Non-Small Cell Lung Cancer (NSCLC). Specifically, it is the most common subtype of NSCLC, accounting for about 40% of all lung cancers. It typically starts in cells that secrete substances like mucus in the outer parts of the lung.

Small Cell Lung Cancer (SCLC) is a completely different type of lung cancer that:

• Makes up about 10-15% of all lung cancers
• Typically starts in the bronchi near the center of the chest
• Is characterized by small, round cells
• Tends to grow and spread much more quickly than adenocarcinoma
• Is more strongly linked to smoking than adenocarcinoma

The distinction is important because these cancers are treated differently:

• Adenocarcinoma often responds well to targeted therapies, especially when specific genetic mutations are present
• SCLC usually requires a different combination of chemotherapy and radiation, and targeted therapies are generally not as effective.

Causes of lung adenocarcinoma

The leading cause of lung cancer, including adenocarcinoma, remains smoking. However, the disease also develops in non-smokers. For instance, in Asia, over 30% of lung cancer patients have never smoked. The exact reasons for this phenomenon are not fully understood, but certain factors increase the risk of cancer development, such as:

• Poor environmental conditions,
• Radiation exposure,
• Chronic lung diseases,
• Contact with asbestos,
• Constant exposure to smoke from fire or open flames.

Genetics also plays a significant role. If a parent was diagnosed with cancer before the age of 50, their children have an elevated risk of developing the disease.

If you notice similar symptoms, consult a doctor immediately. Do not self-medicate, as it can be dangerous to your health!

Symptoms of lung adenocarcinoma

There is no difference in symptoms between adenocarcinoma and other types of lung cancer; the tumor subtype can only be identified through pathomorphological examination (studying tissue structure).

Early-stage symptoms are often absent but may occur if the tumor is located in the primary bronchi. In other cases, symptoms appear when the tumor reaches a significant size or metastasizes to lymph nodes or other organs.

Key symptoms include:

• Persistent cough lasting more than 2–4 weeks despite treatment,
• Severe general weakness,
• Hemoptysis (coughing up blood due to tumor invasion of major bronchi),
• Chest pain unrelated to trauma or body position (caused by cancer cell infiltration into the parietal pleura or ribs),
• Hoarseness (due to intrathoracic lymph node involvement),
• Rapid weight loss without dietary or lifestyle changes,
• Bone pain,
• Headaches or acute neurological symptoms (dizziness, speech impairment, behavioral changes, weakness, or difficulty moving arms or legs, etc.).

Pathology outlines

The development of lung cancer, including adenocarcinoma, involves many causes and pathways, but the predominant role is attributed to the influence of carcinogens. These carcinogens can enter the body through smoking (tobacco smoke contains over 20 carcinogens), inhaling asbestos, exhaust fumes, etc. These substances form new compounds with the DNA structure of lung cells, leading to genetic mutations.

The formation of such compounds is associated with the activation of these carcinogens by proteins, such as cytochrome P450 enzymes encoded by the CYP gene family, as well as enzymes like glutathione-S-transferases (GSTs), which aim to remove toxins from the body.

If these compounds persist and the DNA structure cannot be restored to its original form, critical errors may occur, initiating the transformation of normal cells into malignant ones.

Simply put, inhaled carcinogens interact with cells, disrupting their normal functioning, particularly their DNA replication processes.

However, not every mutation results in cancer. Some mutations have no effect on cell life. According to certain data, between 5 to 9 mutations in the DNA structure are required for the development of a malignant tumor cell and subsequent disease progression. Even so, the formation of a few oncogenic cells does not guarantee cancer development if the body is capable of destroying them. Cancer develops only when the immune system fails to recognize the mutated cells as malignant and does not combat them, leading to tumor growth.

Lung adenocarcinoma metastasis

When a tumor reaches a certain size, it produces specific substances that initiate neolymphangiogenesis and neoangiogenesis—the formation of new lymphatic and blood vessels around the tumor to nourish and support its growth. Once these vessel walls grow, malignant cells can enter the bloodstream or lymphatic system. However, this requires several factors, including reduced local immunity and activation and adhesion of proteins forming extracellular tissue structures.

If tumor cells entering the bloodstream or lymphatic system survive and implant at a new site, they may either remain dormant as micro-metastases (a few cells) or develop further into tumor formations (macro-metastases).

Metastases have a structure and nature similar to the primary tumor, which is why systemic anticancer therapies (e.g., chemotherapy) target all tumor formations simultaneously.

Classification and stages

Based on invasion, adenocarcinoma, like other types of lung cancer, can be classified as:

• Non-invasive (in situ carcinoma) – Malignant cells do not invade deeper tissues.
• Minimally invasive – A small tumor invading tissues to a depth of no more than 5 mm.
• Invasive – Tumors classified as lepidic, typical, papillary, micropapillary, or solid (dense), invading lung tissues deeper than 5 mm.

Modern staging follows international TNM standards:

T (tumor size):

• Tx: The tumor cannot be evaluated (cancer may be suspected if malignant cells are found in sputum, but no tumor is visible during bronchoscopy).
• T0: No primary tumor detected.
• Tis: Carcinoma in situ (a malignant tumor).
• T1: Tumor ≤30 mm, surrounded by lung parenchyma or visceral pleura, not located in the main bronchus:
  • T1mi: Minimally invasive adenocarcinoma.
• T2:
  • Tumor size 31–50 mm.
  • Involves the main bronchus without affecting the carina (tracheal ridge).
  • Involves the visceral pleura covering the lung.
  • Causes volume loss of the lung or obstructive pneumonia; tumor located in the root areas of the lung, involving part or all of the lung.
• T3: Tumor size 51–70 mm or invading the chest wall.
• T4: Tumor size >70 mm or affecting the diaphragm, mediastinum, heart, major vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, tracheal bifurcation, or visceral pericardium, with metastatic nodules in other lobes on the same side.

N (lymph node involvement):

• Nx: Lymph nodes cannot be assessed.
• N0: No metastases in lymph nodes.
• N1: Metastases in lymph nodes near the bronchi and lung root on the tumor side.
• N2: Metastases in lymph nodes in the mediastinum and under the trachea.
• N3: Metastases in lymph nodes in the mediastinum and lung root on the opposite side of the tumor or in supraclavicular lymph nodes.

M (distant metastases):

• M0: No distant metastases.
• M1: Distant metastases are present:
  • M1a: Tumor nodules in the opposite lung, pleural nodules, or metastatic pleural or pericardial effusion (fluid in the pericardial cavity).
  • M1b: Single distant tumor nodule (outside the lungs).
  • M1c: Multiple metastases outside the thoracic cavity affecting one or more organs.

For further localization of distant metastatic sites, additional gradations are used:

• ADP: Adrenal glands.
• BRA: Brain.
• HEP: Liver.
• LYM: Lymph nodes.
• MAR: Bone marrow.
• OSS: Bones.
• OTH: Other organs.
• PER: Abdominal cavity.
• PLE: Pleura.
• PUL: Lung.
• SADP: Adrenal glands.
• SKI: Skin.

Based on the results of all examinations and the determination of each TNM indicator, the stage (1, 2, 3, or 4) is established, which influences further therapy.

When selecting a treatment strategy, the level of PD-L1 protein expression in tumor cell structures is also evaluated, as it helps the tumor evade immune control. This indicator reflects the tumor’s sensitivity to immunotherapy:

• Less than 1% — low expression level;
• 1% to 50% — medium expression level;
• More than 50% — high expression level.

With medium and high expression levels, the expected outcome of immunotherapy is better than with low levels. Such treatment achieves significant success in fighting cancer but does not guarantee the patient’s recovery.

Additionally, the presence or absence of activating driver mutations is crucial, as they contribute to the tumor becoming resistant to previously effective treatment

What are the complications?

Complications can arise both from the primary tumor and due to metastases.

The primary tumor can invade and compress surrounding lung parenchyma, blood vessels, nerves, bronchi, and even ribs, which can lead to:

• Impaired ventilation of lung segments,
• Bleeding,
• Hemoptysis,
• Pain.

Complications related to metastases vary depending on their location. For instance:

• Mediastinal lymph node involvement causes difficulty swallowing food and water, breathing problems (from shortness of breath to choking), and bronchial stenosis, which may be asymptomatic or cause shortness of breath or hemoptysis.
• Brain metastases lead to numbness and immobility of limbs, memory issues, headaches, etc.
• Liver metastases result in liver failure, compression of bile ducts with the development of jaundice, etc.

While metastases can occur in various locations, the most commonly affected areas are lymph nodes, liver, brain, and bones.

Diagnosis

If lung cancer is suspected, it is necessary to consult an oncologist. They will prescribe all required tests to determine the tumor’s location, cancer stage, and treatment strategy.

Diagnosis includes:

• CT or MRI of the brain with contrast — to exclude metastases.
• CT of the chest, abdomen, and pelvis with contrast — to identify other diseases, unrelated malignant tumors, and distant metastases, if any.
• PET-CT — performed for ambiguous diagnoses or unclear findings from CT.
• Tracheobronchoscopy — helps examine the tracheobronchial tree and perform a biopsy of the tumor if it invades the bronchial lumen.
• Core biopsy of the tumor (if feasible and near the ribs) — allows histological examination and determines further treatment tactics.
• Histological examination of the material with immunohistochemical (IHC) and molecular genetic studies (MGS) — recommended for all patients with confirmed lung adenocarcinoma. These analyses identify gene translocations and mutations and assess PD-L1 expression.
• Spirometry — measures the volume of air inhaled and exhaled and the airflow rate through the respiratory tract, essential for determining further treatment tactics (e.g., a spirometry value below 1.5 L indicates the impossibility of removing a lung lobe).
• Blood tests for tumor markers — assess levels of neuron-specific enolase (NSE), soluble fragment of cytokeratin 19 (CYFRA 21-1), and squamous cell carcinoma antigen (SCC).

Further tests depend on the chosen treatment approach.

Differential diagnosis

It is essential to distinguish lung adenocarcinoma from tuberculosis, benign tumors, parasitic lung diseases (e.g., toxoplasmosis and echinococcosis), and lung metastases (i.e., cases where lung adenocarcinoma is a metastasis from another tumor).

What are the treatment options?

The treatment of adenocarcinoma, like any lung cancer, follows national clinical guidelines, incorporating international oncological recommendations.

The treatment approach primarily depends on the disease stage and the functional capacity of the body. Since lung cancers mostly occur in adults and the elderly, adenocarcinoma often coexists with other pathologies of varying severity, which influence the treatment strategy.

If there are no absolute contraindications, the doctor prescribes the most radical treatment method.

• Stage 1: The tumor is surgically removed. Typically, a lobectomy (removal of a lung lobe) is performed. However, depending on the location, form, histological subtype, comorbidities, and other factors, the surgery’s scope may be adjusted. This decision is made individually.
• Stage 2: A combined treatment with chemotherapy and surgery is recommended. The sequence of stages is determined individually, and their order does not affect the outcome. Both “surgery + chemotherapy” and “chemotherapy + surgery” combinations are equally effective.

In recent years, stereotactic radiation therapy has gained popularity for early-stage cancer (Stages 1–2). This “focused” radiation therapy involves high doses over a shorter treatment period. Some studies suggest comparable outcomes between radiation and surgical methods. However, most research indicates better long-term survival rates for patients undergoing radical surgery.

• Stage 3: Treatment depends on lymph node involvement. If metastases are only on the tumor side, combined treatment with preoperative chemotherapy followed by surgery or chemoradiotherapy is performed (for inoperable tumors or high risks). There are many chemotherapy regimens, provided free of charge under the national health insurance system.

If lymph nodes on the opposite side of the chest are affected, the patient is considered inoperable, as surgery becomes ineffective. Chemotherapy combined with radiation therapy is prescribed instead.

• Stage 4: The primary treatment is drug therapy, including targeted therapy (to slow tumor progression) and immunotherapy. These therapies address the tumor and metastatic cells throughout the body. Various regimens and options are determined by an oncologist.

Surgical treatment is rarely indicated at this stage, as tumor removal does not improve prognosis or survival. Most symptoms and complications arise from metastatic foci and systemic intoxication, making surgery ineffective. Additionally, any surgery carries a high risk of complications, including fatal ones.

For widespread tumor processes where chemotherapy is unfeasible due to life-threatening risks, palliative care is prioritized. While not curative, it helps alleviate symptoms. Typically, a single targeted drug is prescribed, available at the nearest outpatient oncology center for home administration per the doctor’s instructions.

Complications of treatment

Complications of surgical treatment occur quite often due to the anatomical complexity of the organs in the chest cavity, the severity of the intervention, and the presence of comorbidities that worsen after surgery. The most dangerous complications include prolonged air leakage (air seeping through wounds on the lung surface), bleeding, bronchial stump failure, empyema, heart rhythm disturbances, etc.

The most common complications of radiation therapy include dermatitis, pneumonitis, and esophagitis.

During chemotherapy, the most frequent complications are anemia, leukopenia, neurotoxicity, cardiomyopathy, toxic damage to the liver and kidneys, etc. The variability of complications is individual, as patients respond differently to medications. Additionally, methods of administration, variations, and chemotherapy regimens differ.

However, almost all of these complications can be treated, so they should not frighten the patient or become a reason to refuse therapy.

Can lung cancer be cured?

The question of whether lung adenocarcinoma can be cured carries deep significance for patients and their families. The answer brings both hope and the need for realistic understanding: lung adenocarcinoma can be cured, particularly when caught early, though outcomes vary significantly based on the stage at diagnosis.

For patients diagnosed at Stage I, when the lung cancer remains localized, the outlook is particularly encouraging. The 5-year survival rate ranges from 68-92%, with surgery and targeted therapy offering genuine possibilities for complete cure. Early detection through regular screening plays a crucial role in achieving these positive outcomes.

Yet it’s important to acknowledge that approximately 40% of patients receive their diagnosis at Stage IV, when the cancer has metastasized. While a complete cure becomes less likely at this advanced stage, modern medicine has made remarkable strides. The 5-year survival rate for stage IV disease has improved from less than 5% to about 10-20% in certain cases, thanks to revolutionary treatments including immunotherapy and targeted medications.

Patients with specific genetic mutations, such as EGFR or ALK, often respond remarkably well to targeted therapies, sometimes achieving years of good quality life. Even when complete cure isn’t possible, lung adenocarcinoma can often be managed as a chronic condition, similar to other long-term health conditions that require ongoing care.

Prognosis and prevention

It is impossible to determine precisely how long a patient with lung adenocarcinoma will live, as each case is individual and not always typical. Naturally, the prognosis will be more favorable at stage 1 with timely treatment than at stages 3–4. However, there are cases when patients with stage 1–2 die earlier. In such cases, the cause of death is usually severe comorbidities (diabetes, arterial hypertension, chronic obstructive pulmonary disease, etc.).

The prognosis depends on:

• The histological subtype of cancer;
• The stage of the disease;
• The patient’s age;
• The presence of specific mutations and translocations;
• Access to specialized treatment;
• The patient’s compliance (adherence to all recommendations of the attending physician);
• The presence and severity of comorbidities, etc.

In oncology, the main indicators of treatment success and effectiveness are overall survival and 5-year survival rates.

Five-year survival rate depending on lung cancer stage:

Stage	Percentage of 5-Year Survivors
1	92–68%
2	53%
3	36–13%
4	10% or lower

Prevention

To reduce the risk of developing the disease, you should:

• Lead a healthy lifestyle;
• Avoid harmful habits;
• Avoid areas with poor air quality (live away from industrial sites and cities with heavy traffic);
• Minimize contact with carcinogens (try not to work in industries where exposure to harmful substances, such as asbestos, is frequent, or follow safety protocols if this is unavoidable);
• Undergo annual X-rays, and those at increased risk (smokers, workers in hazardous industries, patients with chronic inflammatory respiratory diseases) should also have low-dose CT scans;
• Use personal protective equipment (masks, respirators) when working with hazardous materials.

Key takeaways

Lung adenocarcinoma is the most common type of non-small cell lung cancer, typically developing in the outer regions of the lung. It often grows more slowly than other lung cancers, allowing more time for early detection when regular screening is performed.

Advanced molecular testing now guides personalized treatment approaches. Specific genetic mutations like EGFR, ALK, and ROS1 can be targeted with precision therapies, often offering better outcomes than traditional chemotherapy alone for patients with these mutations.

While smoking remains a risk factor, lung adenocarcinoma notably affects a higher proportion of non-smokers compared to other lung cancer types, particularly younger women and East Asian populations. This highlights the importance of considering lung cancer even in patients without a smoking history.