Metastatic Non-Small Cell Lung Cancer

When non-small cell lung cancer spreads beyond the lungs to distant parts of the body, it becomes metastatic—a condition that brings unique challenges but also growing hope through advancing treatments and supportive care approaches.

Table of contents

• What is Metastatic Non-Small Cell Lung Cancer?
• Where the Cancer Can Spread
• Symptoms of Metastatic NSCLC
• How Doctors Diagnose Metastatic NSCLC
• Treatment Approaches
• Understanding Your Outlook
• Managing Symptoms and Quality of Life

What is Metastatic Non-Small Cell Lung Cancer?

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, making up about 80% to 85% of all lung cancer cases^[1]. When NSCLC spreads beyond the lungs to distant parts of the body, it is called metastatic NSCLC. This spreading process is known as metastasis^[2].

NSCLC occurs when abnormal cells in the lungs change and grow out of control^[1]. The cancer cells are larger than those in small cell lung cancer, and they typically grow slower. However, NSCLC may not cause symptoms in its early stages. Because of this, it is often diagnosed after the cancer has already spread to other areas of the body^[1].

There are three main types of non-small cell lung cancer. Adenocarcinoma usually forms in the outer portions of the lung. Squamous cell carcinoma typically starts in the central part of the lungs. Large cell carcinoma can develop in any part of the lungs^[1].

When cancer has metastasized, it means cancer cells have traveled from the main tumor to other areas through two main routes: the bloodstream and the lymphatic system (a network of vessels and tissues that help fight infection)^[2]. About 30% to 40% of all people who receive an NSCLC diagnosis have metastatic cancer at the time of diagnosis^[2].

Metastatic NSCLC is considered stage 4 (stage IV) cancer, which is the most advanced stage. Stage 4 is divided into stage 4A and stage 4B, with stage 4B indicating more widespread disease^[18].

Where the Cancer Can Spread

Like other cancers, NSCLC can spread to any site or organ in the body. However, some locations are more common than others^[2].

According to research, the most common sites where NSCLC spreads include^[5]:

• Bone (34.3% of cases)
• Lung (32.1% of cases)
• Brain (28.4% of cases)
• Adrenal glands (16.7% of cases)
• Liver (13.4% of cases)
• Extrathoracic lymph nodes, or lymph nodes outside the chest area (9.5% of cases)

The adrenal glands are small organs located near the kidneys^[9]. NSCLC can also spread to the pleura, which are the thin layers of tissue that wrap around the outside of the lungs^[9].

Symptoms of Metastatic NSCLC

The symptoms of metastatic NSCLC can vary depending on where the cancer has spread in the body. Some people may experience general lung cancer symptoms, while others develop symptoms specific to the affected organs^[2].

Common symptoms related to lung cancer include^[1]:

• Chest pain
• Chronic cough that does not go away or gets worse
• Coughing up blood or rust-colored spit
• Hoarseness
• Loss of appetite
• Shortness of breath
• Tiredness (fatigue)
• Wheezing
• Unexplained weight loss

When lung cancer spreads to distant organs, additional symptoms may appear depending on the location^[4][12]:

• Bone pain (such as pain in the back or hips) when cancer spreads to the bones
• Headache, weakness or numbness of an arm or leg, dizziness, balance problems, or seizures when cancer spreads to the brain
• Difficulty swallowing
• Swelling of the face, neck, or lymph nodes
• Bulging veins on the neck and head
• Yellowing of the skin and eyes when cancer spreads to the liver

In some cases, NSCLC may not cause symptoms at all^[1]. Experiencing these symptoms does not necessarily mean you have lung cancer, but it is very important to talk to your healthcare team if you experience any of them^[4][12].

How Doctors Diagnose Metastatic NSCLC

Your healthcare provider will perform a physical examination and ask about your symptoms and medical history. If they suspect non-small cell lung cancer, they will recommend tests to diagnose and stage the disease^[1].

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

• Lung biopsy—a procedure where a small sample of tissue is removed from the lung for examination
• Bronchoscopy—a test that gives your healthcare provider a view inside your airways
• Imaging tests such as chest X-rays, CT scans (computed tomography scans that create detailed images of the inside of the body), PET scans (positron emission tomography scans that show how tissues and organs are functioning), and MRI scans (magnetic resonance imaging) of the brain
• Video-assisted thoracic surgery (VATS), which helps your provider get a better look inside your chest

After non-small cell lung cancer has been diagnosed, additional tests are done to find out if cancer cells have spread within the chest or to other parts of the body^[3][8].

Treatment Approaches

Once cancer has metastasized, there is typically no cure. However, treatment often focuses on prolonging a person’s life and improving their quality of life^[2]. Treatment options for metastatic NSCLC have advanced dramatically in recent decades, with new targeted drugs, immunotherapies, improved radiation technologies, and less invasive surgeries^[9].

Treatment for metastatic NSCLC may include one or more of the following approaches^[18]:

• Chemotherapy—medications that kill cancer cells or stop them from growing
• Radiation therapy—the use of high-energy rays to destroy cancer cells
• Targeted drug therapy—medications that target specific genetic changes in cancer cells
• Immunotherapy—treatments that help the body’s immune system fight cancer
• Surgery

Your oncologist (cancer doctor) will work with you to determine which types of treatment are appropriate based on how advanced the cancer is, your overall health, and your immune system strength^[18].

Chemotherapy

Chemotherapy may be offered for stage 4 non-small cell lung cancer if there are no genetic changes (mutations) that can be identified in the lung cancer tumors using cell and tissue studies. You need to be well enough to have chemotherapy^[13].

The most common chemotherapy drug combination used to treat stage 4 NSCLC is cisplatin or carboplatin with gemcitabine. Other chemotherapy combinations may also be used^[13].

Targeted Therapy

Targeted therapy may be offered instead of chemotherapy for stage 4 NSCLC if there are genetic changes to the lung cancer cells. The type of targeted therapy given will depend on the type of genetic mutation identified using cell and tissue studies^[13].

For example, cancer cells that have mutations in the EGFR (epidermal growth factor receptor) gene can be treated with specific targeted therapy drugs. EGFR is a receptor on the surface of cells that sends signals allowing them to grow and divide. A mutation in the EGFR gene can cause cancer cells to grow and divide more than normal^[13].

Other genetic mutations that can be targeted include changes in the ALK (anaplastic lymphoma kinase) gene, ROS1 gene, and KRAS gene^[10].

Immunotherapy

Immunotherapy works by helping the body’s immune system recognize and attack cancer cells. These treatments can be used alone or in combination with chemotherapy depending on your specific situation^[10].

Clinical Trials

Clinical trials—research studies testing new medications—may also be an option. Cancer experts are constantly conducting research to determine whether patients with metastatic lung cancers would benefit from new treatment approaches^[9][18].

Understanding Your Outlook

A diagnosis of metastatic NSCLC can be frightening, but it’s important to know that treatments have advanced significantly. Patients with metastatic lung cancer—both non-small and small cell lung cancers—are living longer than they did 10 years ago^[9].

While metastatic NSCLC is not typically curable, treatments such as chemotherapy, radiation therapy, and immunotherapy can help relieve symptoms, prolong life, and improve quality of life^[6].

Research has shown that certain factors can affect prognosis. In one study, liver and adrenal gland metastases were found to be unfavorable prognostic factors. However, brain and bone metastases were not statistically significant prognostic factors^[5].

It’s important to have open discussions with your doctor about your prognosis and what to expect. Several factors can affect the prognosis and treatment options, including the stage of the cancer, your overall health, and how well treatments work^[3][8].

Managing Symptoms and Quality of Life

Cancer care teams place great emphasis on helping to ensure patients have the quality of life they desire during and after treatment. A wide range of treatments and supportive services are available to help prevent or relieve pain, breathing difficulties, and other symptoms^[9].

Palliative Care

Palliative therapies, which focus on comfort, may help improve quality of life for people with stage 4 lung cancer. Palliative care focuses on relieving chest pain, addressing shortness of breath, removing blockages from airways, reducing buildup of fluid in the lungs (pleural effusion), and treating fluid buildup around the heart^[18].

Treatment for metastatic NSCLC is more than just medical procedures and therapies. It’s important to keep your emotional and mental health in mind as well^[21].

Managing Shortness of Breath

Shortness of breath (dyspnea) is a common problem among people with metastatic NSCLC. Research suggests that up to 60% of patients with advanced lung cancer experience this symptom^[22].

If you experience any worsening in your breathing, it’s important to let your doctor know right away so they can try to identify the main cause and treat it. In addition to medical treatments, there are strategies to help manage shortness of breath, including breathing techniques, relaxation methods, and gentle exercise^[22].

Working with Your Healthcare Team

Open discussions with your care team will help make sure your treatment is on track and that you get the most out of your therapies. These conversations will also help you make decisions that make sense for you and what you need^[21].

You may want to ask your doctor questions like^[21]:

• How do you know if the treatment is working?
• What symptoms or side effects should you look out for?
• What physical changes should you expect?
• Is there anything that might interfere with your treatment?
• Are there limits on what you can do?

You can also ask a caregiver or family member to be your advocate. Some hospitals also have nurse navigators who act as your personal guide during your cancer journey^[21].

Finding Support

Life with cancer can be a roller coaster of emotions. You may feel angry or sad one day and afraid and lonely the next. Sometimes you may need extra support or someone to lean on to help you process the emotional side of cancer^[21].

If you feel overwhelmed, it may help to talk with others who have been through something similar. You may want to join a lung cancer support group. There are a number of in-person and online groups available. There are also options available for caregivers^[21].

Tell your doctor or nurse about your symptoms so they can help you. Treatments such as chemotherapy, radiotherapy, or targeted cancer drugs can help to shrink the cancer, reduce symptoms, and help you feel better^[20].