Unraveling Non-Small Cell Lung Cancer: Symptoms, Stages, Treatments and Beyond

Non-small cell lung cancer is one of the two major types of lung cancer. Lung cancer is the leading cause of cancer-related mortality across the globe. ⁽¹⁾ Lung cancers are primarily of two types, small cell lung cancer, and non-small cell lung cancer.

Non-small cell lung cancer accounts for about 85% of all lung cancer. ^{(2, 3, 4)} Non-small cell lung cancer (NSCLC) is a type of lung cancer that occurs when abnormal cells form and start multiplying in the lung tissues.

Non-small cell lung cancer gets its name because the cancer cells are larger compared to the small cell lung cancer. Non-small lung cancer is usually diagnosed after the cancer has spread to other areas of the body. Thus, early detection and prompt treatment are highly essential.

Non-small cell lung cancer (NSCLC) is primarily of three types. They are:

Currently, adenocarcinoma is the most common type of lung cancer in “never smokers” or “lifelong nonsmokers”. ⁽⁵⁾ Adenocarcinoma forms in cells that secrete mucus and other substances. Such a type of lung cancer develops in the outer portions of the lungs. It mostly affects individuals who smoke or those who used to smoke a lot. However, adenocarcinoma of the lung can also develop in those who have never smoked. Adenocarcinoma is more likely to occur at a younger age compared to other types of lung cancer.

This type of lung cancer starts in squamous cells (the flat cells lining the inside of your airways) and often forms in the central portion of the lungs. Typically, squamous cell carcinoma is associated with a history of smoking.

The Nurses’ Health Study states that the relative risk of squamous cell carcinoma is around 5.5, both among people with a previous duration of smoking of 1 to 20 years, and in people with 20 to 30 years, compared to “never smokers”. ⁽⁶⁾ With a previous smoking duration of 30 years to 40 years, the relative risk of squamous cell carcinoma increases to about 16, and it reaches roughly 22 with more than 40 years of smoking. ⁽⁶⁾

Large cell carcinoma is also known as undifferentiated carcinoma. It is a type of cancer that can form in any part of the lung. It is extremely difficult to treat large cell carcinoma because it grows and spreads very fast.

NOTE: There are also some other types of non-small lung cancer, such as sarcomatoid carcinoma and adenosquamous carcinoma. However, these subtypes are quite less common.

Non-small cell lung cancer is mostly insidious and does not produce any symptoms until the cancer has become well advanced. Symptoms of NSCLC usually depend on the location of the cancer. Shortness of breath and a cough that does not go away are the most common warning signs for this type of lung cancer. Some other symptoms of non-small cell lung cancer include:

• A cough that does not go away and gets worse over time.
• Chest pain and trouble breathing.
• Wheezing and discomfort.
• Coughing up blood.
• Loss of appetite.
• Loss of weight.
• Difficulty swallowing.
• Tiredness and fatigue.
• Swelling in the face or the veins in the neck.

The exact cause of non-small cell lung cancer is not known. However, some risk factors for the condition have been identified. These risk factors include:

• If you either smoke currently or have a history of smoking.
• Exposure to metal and mineral dust.
• Asbestos exposure.
• Air pollution.
• Exposure to radon gas.
• Pulmonary fibrosis.
• Chronic obstructive pulmonary disease (COPD)
• HIV/AIDS
• Radiation therapy to your chest or breast.

Once lung cancer has been diagnosed, tests are performed to find out if cancer cells have spread only within the lungs or to other areas of the body. This process is known as staging.

Stage 0: This is the stage when a group of abnormal cells appears in the top layer of the lung tissue. However, they have not yet spread anywhere else.

Stage I: The tumor in this stage is small and it remains completely inside the lungs.

Stage II: In this stage, the cancer has not spread, but the tumor gets larger than it was in stage I. In this stage, some of the cancer cells might have spread into nearby lymph nodes.

Stage III: By this stage of the cancer, the tumor is extremely large and might have spread into surrounding tissues and lymph nodes.

Stage IV: Stage IV is also called metastatic non-small cell lung cancer. In this stage, cancer cells from the original tumor break and travel from the lung to another area of the body. The bloodstream or lymphatic system carries the cancer cells to other areas of the body.

The doctor performs a physical examination and asks about your symptoms and medical history. If non-small cell lung cancer is suspected, your healthcare provider will recommend specific tests to diagnose and condition and know the stage of the disease. Some of these tests might include:

• Laboratory tests, including blood or urine analyses.
• Chest X-rays that help the doctor to see what is happening inside your lungs,
• CT Scans, that would take detailed 3D images of your organs, muscles, bones, and blood vessels.
• Sputum cytology examines a sample of your mucus that has been coughed up from the lungs.
• Bronchoscopy, which helps your doctor to look inside the airways.
• Thoracoscopy, through which your healthcare provider can get a better look inside of your chest.

Some of the treatment approaches for non-small cell lung cancer include:

Surgery would be recommended by your healthcare provider in case your cancer is in the early stages. The surgeon would remove the tumor and a small amount of healthy tissue around it. An entire lobe (section) of the lung might also be removed by the surgeon. This is known as lobectomy. In some other cases, all or part of the affected lung might have to be removed. This is called lung resection.

NOTE: If the cancer has spread then surgery is not an option.

If patients cannot tolerate surgery, doctors would recommend radiofrequency ablation (RFA). During this procedure, the surgeon destroys the cancer cells by heating your tumor using high-energy radio waves.

Radiation therapy is another way to treat non-small cell lung cancers. The powerful X-ray beams used in radiation therapy kill the cancer cells or restrict them from growing. This therapy can also be performed before surgery to shrink the tumor. Radiation therapy might also be used in combination with other procedures to treat the cancer.

In this treatment procedure drugs or other substances are used to find and attack specific cancer cells without harming health or normal cells. Two types of targeted therapy being used for treating non-small cell lung cancer include monoclonal antibodies and tyrosine kinase inhibitors.

Chemotherapy uses drugs that stop the growth of cancer cells. Chemotherapy can be systemic chemotherapy or regional chemotherapy.

In the case of systemic chemotherapy, the chemotherapy drug is taken by mouth or given through an IV line and the drugs travel through the patient’s bloodstream and reach cancer cells spread throughout the body. However, in case regional chemotherapy, the chemotherapy drugs are directed to a particular area of the patient’s body and target cancer cells in that specific region.

This procedure uses specific drugs that boost the patient’s immune system so it can recognize and destroy cancer cells. The drugs used in immunotherapy are known as checkpoint inhibitors, and include medications like cemiplimab, pembrolizomab, and atezolizumab

The outlook for NSCLC varies. Usually, this type of cancer grows slowly. But in certain cases, NSCLC can grow and spread rapidly, and even lead to rapid death. The cancer can spread within the lungs or can spread to other parts of the body, such as the liver, bone, small intestine, and brain.

Cure rates of non-small cell lung cancer are related to the stage of the cancer and whether the patient has surgery.

Stage I and II cancers have the highest survival and cure rates. In some cases, stage III non-small cell lung cancer can be cured. However, stage IV cancer is seldom cured. In such cases, the primary aim of therapy is to extend and improve the quality of life.

Chemotherapy has been known to improve the quality of life in some patients with stage IV non-small cell lung cancer.

Non-small cell lung cancer is one of the two types of lung cancer that occurs when abnormal cells form and start multiplying in the lung tissues. Usually, non-small cell lung cancer (NSCLC) is diagnosed only when the cancer spreads to other parts of the body, otherwise, it does not show early symptoms. That is why early diagnosis and prompt treatment are required for treating the cancer. Although the exact cause for NSCLC is still unknown, smoking is known to be one of the major risk factors for this type of cancer. Surgery, targeted drug therapy, radiation therapy, immunotherapy, radiofrequency ablation, and chemotherapy are some of the treatment approaches for non-small cell lung cancer. Mostly, lung cancer grows slowly, however, in certain cases, it grows rapidly. The outlook for non-small cell lung cancer depends on the stage of the cancer.

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