Non-small cell lung cancer

Non-small cell lung cancer is the most common type of lung cancer, accounting for about 80% to 85% of all lung cancer cases. It happens when normal cells in your lungs change and grow out of control, usually developing more slowly than other forms of lung cancer but often spreading before symptoms appear.

Table of contents

• What is non-small cell lung cancer?
• Types of non-small cell lung cancer
• Symptoms
• Causes and risk factors
• Complications and spread
• How doctors diagnose the disease
• Treatment options

What is non-small cell lung cancer?

Non-small cell lung cancer (NSCLC) occurs when abnormal cells form and multiply in your lungs. NSCLC is one of two main types of lung cancer. The other is small cell lung cancer (SCLC). NSCLC is the most common type of lung cancer, making up about 80% to 85% of all lung cancer cases^[1][3].

Small cell lung cancer gets its name because the cancer cells look small and round under a microscope. Generally, SCLC is more aggressive than NSCLC. With non-small cell lung cancer, the cancer cells are larger, and they typically grow slower^[1]. The cancer cells are named for the kinds of cells found in the cancer and how the cells look under a microscope^[3].

NSCLC may not cause symptoms. So, even though it grows slower than small cell lung cancer, it’s often diagnosed after the cancer has spread (metastasized) to other areas of your body. That’s why early detection and treatment are so important^[1].

• Lungs
• Bronchi
• Bronchioles
• Alveoli
• Pleura
• Trachea

Types of non-small cell lung cancer

There are three main types of non-small cell lung cancer, categorized by the type of cells affected by cancer^[2]:

• Adenocarcinoma: Usually forms in the outer portions of your lung. Adenocarcinoma is the most common type of NSCLC, representing about 40% of all diagnoses^[1][2]. It begins in the cells that line the small airways, called bronchioles, and often affects both smokers and nonsmokers^[2]. This type tends to grow more slowly than other types of lung cancer, which can help lead to a better outcome^[2].
• Squamous cell carcinoma: Typically starts in the central part of your lungs. It is also called epidermoid carcinoma^[3]. Squamous cell carcinoma is the second most common type of NSCLC, representing 25 to 30% of all NSCLC diagnoses^[2]. This cancer is more closely associated with smoking than any other type of lung cancer^[2].
• Large cell carcinoma: Can develop in any part of your lungs^[1]. It is a rare form of NSCLC, accounting for only 10 to 15% of all diagnoses^[2]. Large cell carcinoma tends to be aggressive^[2]. It is a diagnosis of exclusion, meaning it’s poorly differentiated and cannot be further classified by special testing methods. However, 90% of cases will show squamous, glandular, or neuroendocrine differentiation^[4].

Other types of non-small cell lung cancer include sarcomatoid carcinoma and adenosquamous carcinoma. They’re much less common^[1][3].

Symptoms

Symptoms of non-small cell lung cancer can vary from person to person^[1][2]. Common symptoms can include:

• Chest pain or discomfort
• Chronic cough that doesn’t go away or gets worse over time
• Coughing up blood
• Hoarseness or changing voice
• Loss of appetite
• Shortness of breath or trouble breathing
• Tiredness or fatigue
• Wheezing
• Weight loss for no reason

In some cases, NSCLC may not cause symptoms at all^[1]. In approximately 7 to 10% of cases, lung cancers are diagnosed incidentally in people without symptoms, when a chest X-ray performed for other reasons reveals the disease^[6]. Early lung cancer may not cause any symptoms^[3].

Other symptoms that may occur, often in the late stages, include bone pain or tenderness, eyelid drooping, joint pain, nail problems, shoulder pain or weakness, swallowing difficulty, and swelling of the face^[5]. These symptoms can be due to other, less serious conditions. It is important to talk to your healthcare provider if you have symptoms^[5].

Causes and risk factors

NSCLC occurs when normal cells change and grow out of control. But experts don’t always know why it happens in some people and not in others. However, they have identified some risk factors. A risk factor is something that increases your chances of developing non-small cell lung cancer^[1].

The most common risk factor for lung cancer is a history of smoking. Smoking causes most cases (around 80%) of non-small cell lung cancer^[5]. The risk depends on the number of cigarettes you smoke each day and for how long you have smoked. Being around the smoke from other people (secondhand smoke) also raises your risk of lung cancer^[5]. Your overall exposure to smoking—the longer you smoke and the more packs you smoke in your lifetime—increases the risk for developing this type of cancer^[2].

Other known NSCLC risk factors include^[1][4][5]:

• A family history of lung cancer
• Asbestos exposure
• Exposure to metal and mineral dust
• Exposure to radon, a naturally occurring radioactive gas
• Having respiratory conditions like pulmonary fibrosis (lung scarring) or COPD (chronic obstructive pulmonary disease)
• Radiation therapy to your breast or chest
• Environmental exposure to chemicals such as arsenic, chromium, nickel, coal products, mustard gas, chloromethyl ethers, gasoline, and diesel exhaust
• Constant exposure to high levels of air pollution
• Drinking water that has a high level of arsenic
• Alcohol use

Radiation therapy can also cause primary lung cancer when it is utilized for the treatment of other cancers such as breast cancer and Hodgkin lymphoma^[4].

Some people who have never smoked do develop lung cancer^[5].

Complications and spread

Like many other cancers, non-small cell lung cancer can spread to other parts of your body. Most commonly, it can spread to your^[1]:

• Adrenal glands
• Bones
• Brain
• Liver
• Lymph nodes
• Skin

Most lung cancers are diagnosed at an advanced stage, which means a poorer outlook. The need to diagnose lung cancer at an early and potentially curable stage is obvious, and this has inspired the adoption of lung cancer screening in patients at high risk for lung cancer^[6].

How doctors diagnose the disease

Your healthcare provider will do a physical examination and ask about your symptoms and medical history. You will be asked if you smoke, and if so, how much you smoke and for how long you have smoked. You will also be asked about other things that may have put you at risk of lung cancer, such as exposure to certain chemicals^[5].

When listening to your chest with a stethoscope, your provider may hear fluid around your lungs. This may suggest cancer^[5]. If they suspect non-small cell lung cancer, they’ll recommend certain tests to diagnose and stage the disease^[1].

Medical tests that help diagnose non-small cell lung cancer include^[1][5]:

• Imaging tests: These include chest X-rays or CT scans (computed tomography scans), PET scans (positron emission tomography), and MRI scans (magnetic resonance imaging) of the brain
• Lung biopsy: In most cases, a piece of tissue is removed from your lungs for examination under a microscope^[5]. There are several ways to do this, including bronchoscopy combined with biopsy, CT-scan-directed needle biopsy, endoscopic bronchoscopy ultrasound with biopsy, mediastinoscopy with biopsy, open lung biopsy, and pleural biopsy^[5]
• Bronchoscopy: This gives your healthcare provider a view inside your airways^[1]
• Video-assisted thoracic surgery (VATS): This helps your provider get a better look inside your chest^[1]
• Sputum test: To look for cancer cells^[3]
• Thoracentesis: Sampling of fluid buildup around the lung^[3]

If the biopsy shows cancer, it may be checked for certain genetic changes that may lead to specific treatment^[5]. More imaging tests are done to find out the stage of the cancer. Stage means how big the tumor is and how far it has spread^[5].

Other tests may include^[5]:

• Bone scan
• Complete blood count (CBC)
• Comprehensive metabolic panel

Treatment options

For cancer that’s only in your lung and nowhere else, your healthcare provider may recommend surgery as a first line of treatment. During this procedure, a surgeon removes the tumor and a small amount of healthy tissue around it. If the cancer has spread beyond the original site, all or part of your lung may need to be removed (lung resection)^[1].

Early-stage lung cancer is rare, so many people with NSCLC are diagnosed after the cancer has spread^[1]. Surgery is the treatment of choice for patients with non-small cell lung cancer stages I through IIIA. In addition, patients with resected lung cancer have a high risk of relapse and so are treated with additional chemotherapy after surgery. Patients with stage IIIB and IV NSCLC are usually offered chemotherapy with the option of surgery^[15].

Common treatment approaches include^[2][13]:

• Surgery: To remove the tumor and surrounding tissue
• Chemotherapy: Using drugs to kill cancer cells
• Radiation therapy: Using high-energy rays to destroy cancer cells. Radiation is a reasonable option for treatment in patients who are not candidates for surgery^[15]
• Immunotherapy: Helping your body’s immune system fight cancer
• Targeted therapy: Using drugs that target specific genetic changes in cancer cells. Molecular-targeted therapy plays an increasingly important role in the treatment of advanced NSCLC^[15]

In 2022, the U.S. Food and Drug Administration (FDA) approved the use of the immune checkpoint inhibitor nivolumab, in combination with platinum-doublet chemotherapy, before surgery for patients with resectable NSCLC (tumors 4 centimeters or larger or node positive)^[15].

Because most NSCLC cannot be cured with currently available treatment methods, the appropriate application of skilled palliative care is an important part of treatment. Increasing evidence supports offering palliative care concurrently with standard cancer care at the initial diagnosis of advanced NSCLC^[15]. For example, a clinical trial found that patients with advanced NSCLC who received early palliative care had a better quality of life and, surprisingly, longer survival than those who received standard cancer care alone^[15].