Lung cancer is a type of cancer caused by uncontrolled cell growth in lung tissue. Cancer that originates in other parts of the body and spreads to the lungs (metastasizes) is not considered lung cancer and should be named after the site of origin. Lung cancer is the second most common diagnosis of cancer and the leading cause of cancer mortality. An estimated 2,206,771 people were diagnosed with lung cancer globally in 2020 [1].

The five-year survival rate for people with non-small cell lung cancer, the most common type of lung cancer, is usually between 11% and 17%; it can be lower or higher depending on the type of lung cancer and the extent to which the disease has spread to other organs [2]. Many patients diagnosed with lung cancer have already reached advanced stages because these cancers often do not cause noticeable symptoms and can be mistaken for common diseases.

The average age of patients with lung cancer is around 70 years. Tobacco smoking continues to be the leading cause of lung cancer. Occupational exposure and air pollution can also act independently or together with tobacco smoking in the development of this cancer. However, there are still many patients who develop lung cancer and have never smoked, which may be due to a genetic predisposition. Familial lung cancer is more complex than other familial cancers, and the role of genetic factors in the development of lung cancer is poorly understood [3, 4].

Common symptoms of lung cancer include cough, breathing problems, bloody sputum, chest pain and/or shoulder pain, fatigue, weight loss and frequent lung infections that do not go away or keep recurring. When lung cancer is suspected, X-rays, imaging and blood tests are performed. A biopsy is a procedure in which a small piece of tissue is removed from a tumor to determine if cancer is present [5].

There are two main types of lung cancer: 1. non-small cell lung carcinoma (NSCLC), which accounts for between 85 and 90% of all lung cancers, and 2. small cell lung carcinoma (SCLC), which accounts for the remaining 10% to 15% of all lung cancers. Small cell lung cancer gets its name because the cancer cells look small and round under a microscope, while non-small cell lung cancer cells are larger. SCLC grows faster than NSCLC, and although they are more responsive to chemotherapy, they are still more difficult to treat than NSCLC [4, 6].

NSCLC is categorized into five stages (0-4) depending on the extent of the disease. The stage describes where the lung cancer cells are located, the size of the lung cancer tumor and whether it has spread to other parts of the body. The lower the stage, the less the cancer has spread and the prognosis is better.

Stage 0: An early stage of lung cancer that is only in the top layer of the lungs or bronchus and has not spread.

Stage 1: The cancer has not spread to the lymph nodes or other parts of the body.

Stage 2: These tumors may be larger than those in stage 1 and/or have begun to spread to nearby lymph nodes. The cancer has not spread to distant organs.

Stage 3: The cancer has usually spread to the lymph nodes in the mediastinum (the area in the chest between the lungs).

Stage 4: The cancer has spread, or metastasized, to the lung lining or other parts of the body, usually the bones, brain, adrenal glands and liver [7].

The treatment of patients with NSCLC depends on the stage, age and general condition of the patients. Treatment often involves a combination of different approaches that may include surgery, radiation therapy and systemic therapy such as chemotherapy, targeted molecular agents and immunotherapy.

Surgery is recommended as the first treatment option for people with stage 1 or 2 NSCLC. Options for surgery include:

1. Lobectomy: a type of surgery that removes an entire section (lobe) of the lungs (normally the right lung has three lobes, while the left lung has two lobes).
2. Segmentectomy or wedge removal: involves the removal of part of the lungs, but not an entire lobe.
3. Pneumonectomy: removal of the entire affected lung.

After surgery, radiation therapy may be recommended for patients with stage 1 or 2 NSCLC who have residual tumor at the surgical site or patients who are at high risk of recurrence. Common radiotherapy methods for lung cancer are:

1. External beam radiation therapy (EBRT): a type of radiation therapy that sends a beam of radiation outside the body to the lungs or surrounding areas.
2. Stereotactic body radiation therapy (SBRT), also known as stereotactic ablative radiotherapy (SABR): a type of precision radiotherapy that involves delivering a high dose of radiation very precisely to tumors in the lungs or other organs while limiting the dose to the surrounding healthy organs and tissue.
   

There is no single best treatment for people with stage 3 NSCLC. Recommendations should therefore be individualized by a multidisciplinary (specialty) team. However, the initial treatment for stage 3 NSCLC may include a combination of radiation therapy, chemotherapy and/or surgery.

The identification of gene mutations in lung cancer has led to the development of targeted molecular therapies to improve the survival of subgroups of patients as personalized medicine. For example, patients with stage 1 to 3 NSCLC who have a mutation in a specific gene called EGFR can receive targeted therapy as part of their treatment. Immunotherapy is another option, in addition to conventional therapy, that can be offered to some patients with stage 2 to 3 NSCLC. This may be an option for patients whose cancer cells have programmable cell death ligand 1 (PD-L1) on their surface.

Stage 4 NSCLC has already spread to other organs at the time of diagnosis and can therefore be challenging to cure. Treatment options depend on where and how far the cancer has spread, whether the cancer cells have certain gene or protein changes, and the overall health of the patient. Targeted therapy is the main treatment option for such patients. The patient's tumor will be tested for certain gene mutations (such as in the KRAS, EGFR, ALK, ROS1, BRAF, RET, MET or NTRK genes). If one of these genes is mutated, the patient will likely receive targeted therapy. However, patients who are negative for these mutations may benefit from immunotherapy depending on their PD-L1 expression status. Depending on the PD-L1 expression status, patients may receive chemotherapy alone or in combination with immunotherapy.

Furthermore, surgery and/or radiotherapy can also be performed to treat cancer spreading (metastases) in addition to cancer that is localized in the lungs.

Relapse

If the cancer continues to grow during treatment (progression) or comes back, further treatment will depend on the location and extent of the cancer, what treatments have been given previously, and the person's general health and desire for more treatment. Smaller recurrent tumors in the lungs can sometimes be treated with surgery, radiotherapy or stereotactic radiotherapy. For more extensive recurrences, chemotherapy, immunotherapy or targeted therapy may be appropriate treatment options.

It is important to note that treatment recommendations for lung cancer may vary depending on individual factors and the development of new knowledge and new treatment methods. A thorough assessment by a medical professional is necessary to develop an individualized treatment plan for a patient with lung cancer.

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SCLC has historically been categorized into two stages: limited and extensive. Limited stage lung cancer is found in only one of the two lungs, with or without spread to lymph nodes in the chest area between the two lungs. Extensive stage lung cancer has spread to tissues outside the originally affected lung, such as the opposite lung or distant organs [4].

Standard treatment:

Limited-stage small cell lung cancer is usually treated with both chemotherapy and radiation therapy. Patients with extensive stage small cell lung cancer are treated with chemotherapy alone or in combination with immunotherapy. Radiation therapy can also be beneficial for patients who respond to their first chemotherapy.

Most people with limited-stage small cell lung cancer are treated with chemotherapy in combination with radiation therapy to target the disease in the chest. Patients may also receive radiation therapy to some distant organs, such as the brain, to prevent the development of brain metastases and improve survival. In rare cases of very early stage disease where the only cancer site is a single lesion in one lung, surgery is usually recommended. In such situations, surgery is followed by chemotherapy with or without radiation therapy.

Patients with extensive stage small cell lung cancer are usually treated with chemotherapy and immunotherapy. Surgery is not an option for patients with extensive stage disease. Patients who respond well to chemotherapy may receive radiation therapy to the chest or brain to prevent further development of brain metastases [12].