The most common type of lung cancer is non-small cell lung cancer (NSCLC), which makes up around 90 percent of all lung cancer diagnoses. Like other cancers, NSCLC is generally considered advanced when it has spread outside the area where the tumor first began growing. When it spreads more widely through the body, it’s considered metastatic lung cancer. At the time of diagnosis, 40 percent of people with NSCLC have advanced (stage 4) disease.

Types of NSCLC

The three main types of NSCLC are defined by the different cells where cancer develops:

• Adenocarcinoma accounts for 40 percent of NSCLC cases.
• Squamous cell carcinoma makes up 25 percent to 30 percent of NSCLC cases.
• Large cell carcinoma occurs in about 10 percent to 15 percent of NSCLC cases.

What Is Metastasis?

When cancer spreads outside its original location, this is known as metastasis. Metastasis is a complex process, where cancer cells break away from the primary tumor and travel through the blood or lymph systems to form another tumor in the body.

Different types of cancer form metastases in different locations. In advanced NSCLC, common metastasis sites include the brain, bones, lymph nodes, and liver.

Symptoms of Advanced NSCLC

Lung cancer typically doesn’t cause any symptoms until it is advanced. This means that it is difficult to detect lung cancer early. Over half of all lung cancer cases aren’t diagnosed until tumors have already metastasized to other locations in the body. Approximately 20 percent of people with NSCLC have bone metastases when they are diagnosed.

Early lung cancer symptoms include:

• Shortness of breath
• A persistent cough that may get worse
• Coughing up blood or rust-colored phlegm
• Tiredness or weakness
• Unexplained weight loss
• Hoarseness
• Persistent infections, like pneumonia or bronchitis
• Chest pain that may worsen when coughing, laughing, or breathing deeply

If advanced lung cancer has spread to other sites in the body, it may cause site-specific symptoms.

• Brain symptoms — Headache, balance problems, dizziness, seizures, numbing or weakening of nerves in the arms and legs
• Bone symptoms — Bone pain in the hips, back, or other areas
• Lymph node symptoms — Swollen lymph nodes above the collarbone or in the neck from a buildup of immune cells
• Liver symptoms— Jaundice (yellowing of the eyes and skin)

How Is Advanced NSCLC Diagnosed?

Lung cancer screening can be lifesaving if a person currently smokes or has previously smoked tobacco for many years, is between the ages of 50 and 80, and is fairly healthy. If cancer is found early, treatment is more likely to be successful. If you suspect you may be experiencing symptoms of lung cancer, contact your healthcare team to set up testing.

Your doctor will begin with a medical history and physical exam to identify possible risk factors and signs of lung cancer. If they find anything during the exam that might suggest lung cancer, more tests will be done.

Imaging Tests

Imaging tests can be used to look inside the lungs for cancer and see if it has spread. Some examples of imaging tests include:

• Chest X-ray
• MRI scan
• CT scan
• Positron emission tomography (PET) scan
• Bone scan

Lung-Specific Tests

While symptoms and imaging tests can suggest cancer, the only way to definitively diagnose it is by looking at lung cells under a microscope. The cells can be collected from mucus, from fluid around the lung, or from a biopsy. Depending on the situation, different tests may be used to come to a conclusive diagnosis. These tests may include:

• Sputum cytology — A sample of sputum (mucus) is analyzed under a microscope for cancer cells.
• Needle biopsy — The area where cancer is suspected is numbed, and a hollow needle is inserted there to remove lung tissue. The biopsy is then analyzed for cancer cells.
• Thoracentesis — If there is fluid collected around the lungs, a doctor can insert a hollow needle to drain it. The fluid is collected and analyzed for cancer cells.
• Bronchoscopy — A thin, flexible tube with a light and camera attached to the end is inserted through your nose or mouth and travels down into the lungs. This lets doctors look inside the lungs and airways for any tumors or blockages.

Non-Small Cell Lung Cancer Stages

The severity of cancer is measured by its stage. Lung cancer is typically defined as advanced when it is at stage 3B or later.

Stages of lung cancer range from 0 (also known as carcinoma in situ) through stage 4. A letter with a stage number indicates more precisely how advanced the cancer is. For example, stage 3A is less advanced than stage 3B. While every cancer case is unique, cancer stages help oncologists determine appropriate treatment options and disease outlook.

In stage 3 NSCLC, the lung tumor may be growing into nearby structures or nearby lymph nodes (stage 3A) or structures or lymph nodes throughout the chest (3B). In stage 3C, one or more additional tumors are found in a different lung lobe, or cancer has spread to the chest wall or diaphragm.

In stage 4 NSCLC, cancer has metastasized to other organs in the body and become advanced. Stage 4 can be split into two different stages: stage 4A and stage 4B. Stage 4A indicates the cancer has spread to the other lung or the fluid surrounding the lungs and heart. Stage 4B indicates the cancer has spread to distant sites around the body.

What Causes Advanced NSCLC?

Cancer is caused when certain genetic mutations (or changes) develop in a cell and lead to uncontrolled growth. The most common cause of lung cancer is smoking tobacco. The Moffitt Cancer Center estimates men who smoke are 23 times more likely to develop NSCLC, and women are 13 times more likely.

Lung cancer can also develop in people who have never smoked, usually through environmental exposures or the inheritance of gene changes from family members. These cases occur most often in younger people. Environmental irritants, like air pollution, radon, asbestos, and other chemicals, can cause mutations in lung cells.

How Is Advanced NSCLC Treated?

Advanced non-small cell lung cancer treatment depends on staging and a person’s overall health and lung function. Other factors such as the size of the tumor, where it is located, whether it has spread to lymph nodes, and how well you tolerate treatment are also considerations. Chemotherapy, radiation therapy, and targeted therapies are the most common treatment options for NSCLC.

New advances in immunotherapy and targeted therapy are also expanding treatment options and improving survival rates. You can also ask your oncology team about clinical trials for new medications in development that may be appropriate for you. Your doctor may recommend palliative care to help with pain management, fluid buildup in lungs and airways, and improved quality of life with advanced NSCLC.

Your treatment plan may include a combination of different therapies. Always discuss potential side effects with your doctor before starting a new treatment.

Chemotherapy

Chemotherapy is a broad term used to describe drugs that target and kill rapidly dividing cells in the body. Chemotherapy drugs are given through an intravenous (IV) infusion or taken by mouth. The drugs travel through the bloodstream and reach almost every part of the body to target and kill cancer cells.

Some common chemotherapy drugs for NSCLC include:

• Gemcitabine (Gemzar)
• Paclitaxel
• Pemetrexed (Alimta)
• Vinorelbine (Navelbine)

Radiation Therapy

Radiation therapy commonly uses an intense beam of radiation to kill cancer cells and shrink tumors. This type of radiation therapy is similar to that used in X-rays, but it’s much more concentrated for cancer treatment. Radiation therapy works by damaging the DNA of cancer cells beyond repair, causing the cells to stop dividing or die. Other types of radiation therapy include brachytherapy, which attacks cancer cells from inside the body using small radioactive pellets, and proton therapy.

Radiation therapy is also used in advanced NSCLC as a palliative treatment for improving quality of life by relieving or avoiding symptoms.

Immunotherapy

Immunotherapy is a relatively recent advancement in the treatment of lung cancer. In immunotherapy, human-made proteins (known as monoclonal antibodies) help activate the immune system to target and kill cancer. Some immunotherapy drugs are also known as checkpoint inhibitors because they interfere with molecules in the immune system that block the body from attacking cancer cells.

Immunotherapy drugs for NSCLC include:

• Atezolizumab (Tecentriq)
• Cemiplimab-rwlc (Libtayo)
• Durvalumab (Imfinzi)
• Nivolumab (Opdivo)
• Pembrolizumab (Keytruda)

Targeted Therapy

Targeted therapy refers to a type of treatment that works by “targeting” specific mutations, abnormalities, and growth factors in cancer. These drugs can only be used in people who have specific mutations in their cancer cells, which are indicated in biomarker testing. Because targeted therapy drugs are so specific, this helps minimize damage to other cells and causes fewer side effects than traditional chemotherapy.

Classes of targeted therapy for advanced NSCLC include tyrosine kinase inhibitors, antibody-drug conjugates (ADCs), and angiogenesis inhibitors, which work in different ways to slow the growth or encourage the death of lung cancer cells.

Many targeted therapy drugs may be used to treat NSCLC, including:

• Afatinib (Gilotrif)
• Amivantamab-vmjw (Rybrevant)
• Bevacizumab (Avastin)
• Dacomitinib (Vizimpro)
• Ramucirumab (Cyramza)
• Sotorasib (Lumakras)
• Zenocutuzumab-zbco (Bizengri)

Surgery

Surgery may be an option for some people with advanced NSCLC. However, unlike some cases of early-stage lung cancer, surgery cannot remove cancer completely in advanced NSCLC.

Read more about each category of lung cancer treatment in the related article Treatment Options for Advanced NSCLC.

Talk With Others Who Understand

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