Factors that may affect lung cancer risk

Different cancers have different risk factors. Some risk factors, like smoking, can be changed. Others, like a person’s age or family history, can’t be changed. But having a risk factor, or even several, does not mean that you will get the disease. And some people who get the disease may have few or no known risk factors. Several risk factors can make you more likely to develop lung cancer. These factors are related to the risk of lung cancer in general.

Risk factors you can change

Tobacco smoke

Smoking is by far the leading risk factor for lung cancer. About 80% of lung cancer deaths are thought to result from smoking, and this number is probably even higher for small cell lung cancer (SCLC). It’s rare for someone who has never smoked to have SCLC.

The risk of lung cancer for people who smoke is many times higher than for people who don’t smoke. The longer you smoke and the more packs a day you smoke, the greater your risk.

Cigar smoking, pipe smoking, and menthol cigarette smoking are almost as likely to cause lung cancer as cigarette smoking. Smoking low-tar or “light” cigarettes increases lung cancer risk as much as regular cigarettes.

Secondhand smoke

If you don’t smoke, breathing in the smoke of others (called secondhand smoke or environmental tobacco smoke) can increase your risk of developing lung cancer. Secondhand smoke is the third most common cause of lung cancer in the United States.

Exposure to radon

Radon is a naturally occurring radioactive gas that results from the breakdown of uranium in soil and rocks. You can’t see, taste, or smell it. According to the US Environmental Protection Agency (EPA), radon is the second-leading cause of lung cancer in the United States, and it’s the leading cause among people who don’t smoke.

Outdoors, there is so little radon that it is not likely to be dangerous. But indoors, radon can be more concentrated. Breathing it in exposes your lungs to small amounts of radon. This may increase a person’s risk of lung cancer.

Homes and other buildings in nearly any part of the country can have high indoor radon levels (especially in basements).

Exposure to asbestos

People who work with asbestos (such as in mines, mills, textile plants, places where insulation is used, and shipyards) are several times more likely to die of lung cancer. Lung cancer risk is much greater in workers exposed to asbestos who also smoke. It’s not clear how much low-level or short-term exposure to asbestos might raise lung cancer risk.

People exposed to large amounts of asbestos also have a greater risk of developing mesothelioma, a type of cancer that starts in the pleura (the lining surrounding the lungs). 

In recent years, government regulations have greatly reduced the use of asbestos in commercial and industrial products. It’s still present in many homes and other older buildings, but it’s not usually considered harmful as long as it’s not released into the air by deterioration, demolition, or renovation. 

Exposure to other cancer-causing agents in the workplace

Other carcinogens (cancer-causing agents) found in some workplaces that can increase lung cancer risk include:

• Radioactive ores, such as uranium
• Inhaled chemicals, such as arsenic, beryllium, cadmium, silica, vinyl chloride, nickel compounds, chromium compounds, coal products, mustard gas, and chloromethyl ethers
• Diesel exhaust

The government and industry have taken steps in recent years to help protect workers from many of these exposures. But the dangers are still there, so if you work around these agents, be careful to limit your exposure whenever possible.

Taking certain dietary supplements

Studies looking at the possible role of vitamin supplements in reducing lung cancer risk have had disappointing results. In fact, multiple studies found that people who smoked and took beta-carotene supplements actually had an increased risk of lung cancer. The results of these studies suggest that people should avoid taking beta-carotene supplements.

Arsenic in drinking water

Studies of people in parts of Southeast Asia and South America with high levels of arsenic in their drinking water have found a higher risk of lung cancer. In most of these studies, the levels of arsenic in the water were many times higher than those typically seen in the United States, even areas where arsenic levels are above normal.

Risk factors you cannot change

Previous radiation therapy to the lungs

People who have had radiation therapy to the chest for other cancers are at higher risk for lung cancer, particularly if they smoke. Examples include people who have been treated for Hodgkin lymphoma or women who were treated with chest radiation for breast cancer.

Air pollution

In cities, air pollution, such as from diesel exhaust, appears to raise the risk of lung cancer slightly. This risk is far less than the risk caused by smoking, but about 1% to 2% of all deaths from lung cancer are thought to be due to outdoor air pollution.

Personal or family history of lung cancer

If you have had lung cancer, you have a higher risk of developing another lung cancer.

Brothers, sisters, and children of people who have had lung cancer may have a slightly higher risk of lung cancer themselves, especially if the relative was diagnosed at a younger age. It’s not clear how much of this risk might be due to shared genes among family members and how much might be from shared household exposures (such as tobacco smoke or radon).

Researchers have found that genetics do play a role in some families with a strong history of lung cancer. 

Factors with uncertain or unproven effects on lung cancer risk

Smoking marijuana

There are reasons to think smoking marijuana might increase lung cancer risk.

• Marijuana smoke contains tar and many of the same cancer-causing substances that are in tobacco smoke. (Tar is the sticky, solid material that remains after burning, which is thought to contain most of the harmful substances in smoke.)
• Marijuana cigarettes (joints) are typically smoked all the way to the end, where tar content is the highest.
• Marijuana is inhaled very deeply, and the smoke is held in the lungs for a long time, which gives any cancer-causing substances more opportunity to deposit in the lungs.
• Because marijuana is still illegal in many places, it may not be possible to control what other substances it might contain.

It’s been hard to study whether there is a link between marijuana and lung cancer because marijuana has been illegal in many places for so long, and it’s not easy to gather information about the use of illegal drugs. Also, in studies that have looked at past marijuana use in people who had lung cancer, most of the people who smoked marijuana also smoked cigarettes. This can make it hard to know how much any increased risk is from tobacco and how much might be from marijuana. We do know that smoking marijuana will irritate your lungs and possibly increase your risk of getting more lung infections. More research is needed to know the cancer risks from smoking marijuana.

E-cigarettes

E-cigarettes are a type of electronic nicotine delivery system. Most e-cigarettes contain nicotine, so the Food and Drug Administration (FDA) classifies them as “tobacco products.”  The FDA states that e-cigarettes cause health risks, including lung damage. Furthermore, e-cigarettes have not been shown to improve your chances of quitting smoking. Whether e-cigarettes directly increase your risk of lung cancer is not yet known.

How smoking leads to lung cancer

Smoking tobacco is by far the leading cause of lung cancer. About 85% of lung cancer deaths in 2025 are expected to be caused by smoking, and many others will be caused by exposure to secondhand smoke.

Smoking is clearly the strongest risk factor for lung cancer, but it often interacts with other factors. People who smoke and are exposed to other known risk factors, such as radon and asbestos, are at an even higher risk. Not everyone who smokes gets lung cancer, so other factors like genetics probably play a role as well .

Causes in people who don’t smoke

Not all people who get lung cancer smoke. Many people with lung cancer formerly smoked, but many others never smoked at all.

Lung cancer in people who don’t smoke can be caused by exposure to radon, secondhand smoke, air pollution, or other factors. Workplace exposures to asbestos, diesel exhaust, or other chemicals can also cause lung cancers in some people who don’t smoke.

Some people with no known risk factors may develop lung cancer. This may be due to random events that don’t have an outside cause, but it also may be due to factors that we don’t yet know about.

Lung cancers in people who don’t smoke are often different from those that occur in people who do. They tend to develop in younger people and often have certain gene changes that are different from those in tumors found in people who smoke. In some cases, these gene changes can be used to guide treatment.

Gene changes that may lead to lung cancer

DNA is the molecule in our cells that makes up our genes, which control how our cells function. DNA, which comes from both our parents, affects more than just how we look. It also can influence our risk for developing certain diseases, including some kinds of cancer.

Some genes help control when cells grow, divide to make new cells, and die:

• Genes that help cells grow, divide, or stay alive are called oncogenes.
• Genes that help control cell division or cause cells to die at the right time are called tumor suppressor genes.

Cancers can be caused by DNA changes that turn on oncogenes or turn off tumor suppressor genes. Changes in many different genes are usually needed to cause lung cancer. There are primarily two types of gene mutations (changes): germline mutations and somatic mutations.

Inherited gene changes (germline mutations)

Inherited gene changes, or germline mutations, are gene changes that you inherit from your parents. These are the mutations in your DNA that you inherit from the egg and sperm cells when you are conceived.  Some people inherit DNA mutations  from their parents that may increase their risk for developing certain cancers.  Historically, germline mutations were not thought to cause very many lung cancers. However, recent studies have shown there may be a benefit to test all patients with lung cancer for germline mutations. If germline mutations are found, it would not only show that you were at an increased hereditary risk for developing lung cancer, but it could also help guide discussions about the best way to treat your lung cancer. If you have lung cancer and are also found to have a certain germline mutation, you may respond well to that mutation’s targeted therapy.

Examples of possible germline mutations for patients with lung cancer include: CHEK2, ATM, TP53, BRCA1, EGFR, APC, and PALB2. Studies are ongoing to better understand the role of germline mutations in lung cancer. Regardless of whether you carry a higher hereditary risk for lung cancer, doctors recommend that all people avoid tobacco smoke and other exposures that will increase cancer risk.

Acquired gene changes (somatic mutations or “driver mutations”)

Acquired gene changes, or somatic mutations, may occur in any individual cell and cannot be inherited. Somatic mutations refer to DNA changes within cells that were not passed from your parents, but rather were acquired during your lifetime. Certain somatic mutations can affect the cell’s ability to control its own growth, and will eventually transform a non-cancer cell to become a cancer cell. These somatic mutations are also known as “driver mutations.” If your tumor is found to have a driver mutation, you will likely respond well to targeted therapy.

For patients with advanced non-small cell lung cancer, it is recommended that the lung mass or a metastatic mass be tested for driver mutations. It is standard practice to test for the following driver mutations: EGFR, ALK, ROS1, MET, RET, BRAF, and NTRK. If any of these driver mutations are found, initial treatment with a targeted therapy (rather than chemotherapy) would be recommended. Although these mutations can be found in any patient with lung cancer, nonsmokers with lung cancer are more likely to have a driver mutation.

Detection and Diagnosis

Catching cancer early often allows for a higher likelihood of successful treatment. Some early cancers may have signs and symptoms that can be noticed, but that is not always the case.

Screening options for lung cancer

Regular chest x-rays have been studied as a screening test for people at higher risk for lung cancer, but they haven’t been shown to help most people live longer, and therefore they aren’t recommended for lung cancer screening.

At present, a test known as a low-dose CT (LDCT) scan is used to screen people at higher risk (mainly because they smoke or used to smoke) for lung cancer. LDCT scans can help find abnormal areas in the lungs that may be cancer. Research has shown that unlike chest x-rays, yearly LDCT scans to screen people at higher risk of lung cancer can save lives. For these people, getting yearly LDCT scans before symptoms start helps lower the risk of dying from lung cancer.

Reasons to screen people at higher risk for lung cancer

In the United States, lung cancer is the second most common cancer. It’s also the leading cause of death from cancer.

If lung cancer is found at an earlier stage, when it is small and before it has spread, it is more likely to be treated successfully. Lung cancer screening is recommended for certain people who smoke or used to smoke, but who don't have any signs or symptoms.

Usually symptoms of lung cancer don’t appear until the disease is already at an advanced stage. Even when lung cancer does cause symptoms, many people may mistake them for other problems, such as an infection or long-term effects from smoking. This may delay the diagnosis. If you have symptoms that could be from lung cancer, see your doctor right away. (People who already have symptoms that might be from lung cancer may need tests such as CT scans to find the cause, which in some cases may be cancer. But this kind of testing is for diagnosis and is not the same as screening.)

The most common lung cancer symptoms

The most common symptoms of lung cancer are:

• A cough that does not go away or gets worse
• Coughing up blood or rust-colored sputum (spit or phlegm)
• Chest pain that is often worse with deep breathing, coughing, or laughing
• Hoarseness
• Loss of appetite
• Unexplained weight loss
• Shortness of breath
• Feeling tired or weak
• Infections such as bronchitis and pneumonia that don’t go away or keep coming back
• New onset of wheezing

Signs and symptoms of lung cancer that has spread

If lung cancer spreads to other parts of the body, it may cause:

• Bone pain (like pain in the back or hips)
• Nervous system changes (such as headache, weakness or numbness of an arm or leg, dizziness, balance problems, or seizures), from cancer spread to the brain
• Yellowing of the skin and eyes (jaundice), from cancer spread to the liver
• Swelling of lymph nodes (collection of immune system cells) such as those in the neck or above the collarbone

Syndromes caused by lung cancer

Some lung cancers can cause syndromes, which are groups of specific symptoms.

Horner syndrome

Cancers of the upper part of the lungs are sometimes called Pancoast tumors. These tumors are more likely to be non-small cell lung cancer (NSCLC) than small cell lung cancer (SCLC).

Pancoast tumors can affect certain nerves to the eye and part of the face, causing a group of symptoms called Horner syndrome:

• Drooping or weakness of one upper eyelid
• A smaller pupil (dark part in the center of the eye) on the same side of the face
• Little or no sweating on the same side of the face

Pancoast tumors can also sometimes cause severe shoulder pain.

Superior vena cava syndrome

The superior vena cava (SVC) is a large vein that carries blood from the head and arms down to the heart. It passes next to the upper part of the right lung and the lymph nodes inside the chest.

• Tumors in this area can press on the SVC, which can cause the blood to back up in the veins.
• This blood backup can lead to swelling in the face, neck, arms, and upper chest (sometimes with a bluish-red skin color), as well as trouble breathing.
• It can also cause headaches, dizziness, and a change in consciousness if it affects the brain.

While SVC syndrome can develop gradually over time, in some cases it can become life-threatening, and needs to be treated right away.

Paraneoplastic syndromes

Some lung cancers may cause problems in distant tissues and organs, even though the cancer has not spread to those places. These problems are called paraneoplastic syndromes. Paraneoplastic syndromes can affect your nervous system (paraneoplastic neurologic syndrome) or your endocrine system (paraneoplastic endocrine syndrome). Sometimes these syndromes may be the first symptoms of lung cancer. Because the symptoms affect other organs, a disease other than lung cancer may first be suspected as causing them.

Paraneoplastic syndromes can happen with any lung cancer but are more often associated with small cell lung cancer (SCLC).

In paraneoplastic endocrine syndrome, the lung tumor makes hormone-like substances that enter the bloodstream and affect distant organs. Examples include:

• SIADH (syndrome of inappropriate anti-diuretic hormone): There are many diseases that can cause SIADH. Cancer is one of them. In this condition, the cancer cells make ADH (anti-diuretic hormone), a hormone that causes the kidneys to keep too much water in the body. This lowers salt levels in the blood. Symptoms of SIADH can include fatigue, loss of appetite, muscle weakness or cramps, nausea, vomiting, restlessness, and confusion. Without treatment, severe cases may lead to seizures and coma.
• Cushing syndrome: There are many reasons why a person may develop Cushing syndrome. Cancer is one of them and is called ectopic Cushing syndrome. In this condition, the cancer cells make ACTH (adrenocorticotropic hormone), a hormone that causes the adrenal glands to make cortisol. This can lead to symptoms that include weight gain, easy bruising, weakness, drowsiness, and fluid retention. Cushing syndrome can also cause high blood pressure, high blood sugar levels, or even diabetes.
• Hypercalcemia: The tumor can make a hormone called parathyroid hormone-related peptide (PTHrP) that acts on the bones and kidney to increase the level of calcium in the blood. High levels of calcium in the blood (hypercalcemia can cause frequent urination, thirst, constipation, nausea, vomiting, belly pain, weakness, fatigue, dizziness, and confusion.

In paraneoplastic neurologic syndrome, the tumor can cause the body’s immune system to mistakenly attack parts of the nervous system (brain, spinal cord, nerves), rather than the cancer cells. Examples include:

• Lambert-Eaton syndrome: In this syndrome, the tumor may cause the immune system to attack the neuromuscular junction, which is the place where nerves communicate with muscle. This can lead to muscle weakness and issues with walking, speaking, and swallowing.  One of the first signs may be trouble getting up from a sitting position. Later, muscles around the shoulder may become weak.
• Paraneoplastic cerebellar degeneration: This disease can be caused by many different cancers, including small cell lung cancer. The immune system makes antibodies meant to attack the tumor, but instead mistakenly attacks an area of the brain called the cerebellum. This can lead to loss of balance and unsteadiness in arm and leg movement, trouble speaking, trouble swallowing, and vision changes.
• Paraneoplastic limbic encephalitis: The limbic system is a part of the brain that is in charge of storing memory, and controlling emotions and behavior, as well as blood pressure and heart rate. The tumor may cause the immune system to damage the limbic system. This can lead to memory loss, personality changes, mood changes, sleep issues, and seizures.

Many of these symptoms are more likely to be caused by something other than lung cancer. Still, if you have any of these problems, it’s important to see your doctor right away so the cause can be found and treated, if needed.

Medical history and physical exam

Your doctor will ask about your medical history to learn about your symptoms and possible risk factors. They will also examine you to look for signs of lung cancer or other health problems.

If the results of your history and physical exam suggest you might have lung cancer, more tests will be done. These could include imaging tests and/or biopsies of the lung.

Imaging tests to look for lung cancer

Imaging tests use x-rays, magnetic fields, sound waves, or radioactive substances to create pictures of the inside of your body. Imaging tests might be done for a number of reasons both before and after a diagnosis of lung cancer, including:

• To look at suspicious areas that might be cancer
• To learn how far cancer might have spread
• To help determine if treatment is working
• To look for possible signs of cancer coming back after treatment

Chest x-ray

A chest x-ray is often the first test your doctor will do to look for any abnormal areas in the lungs. If something suspicious is seen, your doctor may order more tests.

Computed tomography (CT) scan

A CT scan uses x-rays to make detailed cross-sectional images of your body. Instead of taking 1 or 2 pictures, like a regular x-ray, a CT scanner takes many pictures and a computer then combines them to show a slice of the part of your body being studied.

A CT scan is more likely to find lung tumors than routine chest x-rays. It can also show the size, shape, and position of any lung tumors and can help find enlarged lymph nodes that might contain cancer that has spread. This test can also be used to look for masses in other parts of the body that might be due to the lung cancer spread.

CT-guided needle biopsy: If a suspected area of cancer is deep within your body, a CT scan might be used to guide a biopsy needle into this area to get a tissue sample to check for cancer.

Magnetic resonance imaging (MRI) scan

Like CT scans, MRI scans show detailed images of soft tissues in the body. But MRI scans use radio waves and strong magnets instead of x-rays. MRI scans are most often used to look for possible spread of lung cancer to the brain, spinal cord, or liver.

Positron emission tomography (PET) scan

For a PET scan, a slightly radioactive form of sugar (known as fluorodeoxyglucose [FDG]) is injected into the blood and collects mainly in cancer cells. This is because cancer cells tend to take up more sugar (or glucose) than normal cells do.

PET/CT scan: Often a PET scan is combined with a CT scan using a special machine that can do both at the same time. This lets the doctor compare areas of higher radioactivity on the PET scan with a more detailed picture on the CT scan. This is the type of PET scan most often used in patients with cancer. PET/CT scans are used for cancer staging, which is to see if and where the cancer has spread. While they can be used to look at most organs in the body, they are not useful for looking at the brain or spinal cord.

Bone scan

For a bone scan, a small amount of low-level radioactive material is injected into the blood and collects mainly in abnormal areas of bone. It can help show if a cancer has spread to the bones.

Tests to diagnose lung cancer

Symptoms and the results of certain tests may strongly suggest that a person has lung cancer, but the actual diagnosis is made by looking at lung cells in the lab. The cells can be taken from a suspicious area using a needle or surgery (needle biopsy), fluid removed from the area around the lung (thoracentesis), or lung secretions (mucus you cough up from the lungs). The choice of which test(s) to use depends on the situation.

Needle biopsy

Doctors often use a hollow needle to get a small sample from a suspicious area (mass). An advantage of needle biopsies is that they don’t require an incision. The drawback is that they remove only a small amount of tissue, and in some cases, the amount of tissue removed might not be enough to both make a diagnosis and to perform more tests on the cancer cells that can help doctors choose anticancer drugs. The main types of needle biopsies are: fine needle aspiration (FNA) biopsy and core needle biopsy (CNB).

Fine needle aspiration (FNA) biopsy

A syringe with a very thin, hollow needle is used to withdraw (aspirate) cells and small fragments of tissue. FNA biopsy may be done to check for cancer in very small masses or the lymph nodes located around the lungs. Transtracheal FNA or transbronchial FNA is done by passing the needle through the wall of the trachea (windpipe) or bronchi (the large airways leading into the lungs) during a bronchoscopy or endobronchial ultrasound.

In some patients, an FNA biopsy is done during an endoscopic esophageal ultrasound (described below) by passing the needle through the wall of the esophagus.

Core biopsy

A larger needle is used to remove one or more small cores of tissue. Samples from core biopsies are often preferred because they are larger than FNA biopsies.

Core biopsies can be done during many lung procedures and/or surgeries. One example would be during a Transthoracic needle biopsy, where the biopsy needle is put through the skin on the chest wall. The doctor guides the needle into the area while looking at the lungs with either fluoroscopy, which is like an x-ray, or a CT scan. A possible complication of this procedure is that air may leak out of the lung at the biopsy site and into the space between the lung and the chest wall. This is called a pneumothorax. It can cause part of the lung to collapse and sometimes cause trouble breathing. If the air leak is small, it often gets better without any treatment. Large air leaks are treated by inserting a chest tube (a small tube into the chest space), which sucks out the air over a day or two, after which it usually heals on its own.

Thoracentesis

If fluid has collected around the lungs (called a pleural effusion), doctors can remove some of the fluid to find out if it is caused by cancer spreading to the lining of the lungs (pleura). The buildup might also be caused by other conditions, such as heart failure or an infection.

For a thoracentesis, the skin is numbed and a hollow needle is inserted between the ribs to drain the fluid. The fluid is checked in the lab for cancer cells. Other tests of the fluid are also sometimes useful in telling a malignant (cancerous) pleural effusion from one that is not.

If a malignant pleural effusion has been diagnosed and is causing trouble breathing, a thoracentesis may be repeated to remove more fluid which may help a person breathe better.

Sputum cytology

A sample of sputum (mucus you cough up from the lungs) is looked at in the lab to see if it has cancer cells. The best way to do this is to get early-morning samples 3 days in a row. This test is more likely to help find cancers that start in the major airways of the lung, such as squamous cell lung cancers. It might not be as helpful for finding other types of lung cancer. If your doctor suspects lung cancer, further testing will be done even if no cancer cells are found in the sputum. This form of testing is not usually used unless the other methods are felt to be too dangerous for the patient.

Tests to look for lung cancer

If lung cancer has been found, it’s often important to know if it has spread to the lymph nodes in the space between the lungs (mediastinum) or other nearby areas. This is especially important for a person with early-stage lung cancer, and can affect  their treatment options. Several types of tests can be used to look for this cancer spread.

Bronchoscopy

Bronchoscopy can help the doctor find tumors or blockages in the airways of the lungs, which can often be biopsied during the procedure.

Electromagnetic navigation bronchoscopy uses a bronchoscope to biopsy a tumor in the outer part of the lung. First, CT scans are used to create a virtual bronchoscopy. The abnormal area is identified, and a computer helps guide a bronchoscope to the area so that it can be biopsied. The bronchoscope used has some special attachments that allow it to reach farther than a regular bronchoscope. This takes special equipment and training.

Endobronchial ultrasound

An endobronchial ultrasound can be used to see the lymph nodes and other structures in the area between the lungs if biopsies need to be taken in those areas.

Endoscopic esophageal ultrasound

An endoscopic esophageal ultrasound goes down into the esophagus, where it can show the nearby lymph nodes which may contain lung cancer cells. Biopsies of the abnormal lymph nodes can be taken at the same time as the procedure.

Mediastinoscopy and mediastinotomy

These procedures may be done to look more directly at and get samples from the structures in the mediastinum (the area between the lungs). The main difference between the two is in the location and size of the incision.

A mediastinoscopy is a procedure that uses a lighted tube inserted behind the sternum (breast bone) and in front of the windpipe to look at and take tissue samples from the lymph nodes along the windpipe and the major bronchial tube areas. If some lymph nodes can’t be reached by mediastinoscopy, a mediastinotomy may be done so the surgeon can directly remove the biopsy sample. For this procedure, a slightly larger incision (usually about 2 inches long) between the left second and third ribs next to the breastbone is needed.

Thoracoscopy

Thoracoscopy can be done to find out if cancer has spread to the spaces between the lungs and the chest wall, or to the linings of these spaces. It can also be used to sample tumors on the outer parts of the lungs, as well as nearby lymph nodes and fluid, and to assess whether a tumor is growing into nearby tissues or organs. This procedure is not often done just to diagnose lung cancer, unless other tests such as needle biopsies are unable to get enough samples for the diagnosis. Thoracoscopy can also be used as part of the treatment to remove part of a lung in some early-stage lung cancers. This type of operation, known as video-assisted thoracic surgery (VATS), is described in Surgery for Non-Small Cell Lung Cancer.

Lung function tests

Lung (or pulmonary) function tests (PFTs) are often done after lung cancer is diagnosed to see how well your lungs are working. This is especially important if surgery might be an option in treating the cancer. Surgery to remove lung cancer may mean removing part or most of a lung, so it’s important to know how well your lungs are working beforehand. Some people with poor lung function (like those with lung damage from smoking) don’t have enough healthy lung to withstand removing even part of a lung. These tests can give the surgeon an idea of whether surgery is a good option, and if so, how much lung can safely be removed.

There are different types of PFTs, but they all basically have you breathe in and out through a tube that is connected to a machine that measures airflow.

Sometimes PFTs are coupled with a test called an arterial blood gas. In this test, blood is removed from an artery (instead of from a vein, like most other blood tests) so the amount of oxygen and carbon dioxide can be measured.

Lab tests of biopsy and other samples

Samples that have been collected during biopsies or other tests are sent to a pathology lab. A pathologist will look at the samples and may do other special tests to diagnose and better classify the cancer. (Cancers from other organs also can spread to the lungs. It’s very important to find out where the cancer started, because treatment is different depending on the origin of the cancer.)

The results of these tests are described in a pathology report, which is usually available within a week. If you have any questions about your pathology results or any diagnostic tests, talk to your doctor. If needed, you can get a second opinion of your pathology report by having your tissue samples sent to a pathologist at another lab.

Molecular testing (genomic testing) of lung tumor

In some cases, especially for non-small cell lung cancer (NSCLC), doctors may test for specific gene changes in the cancer cells, which could mean certain targeted drugs might help treat the cancer. For example:

• About 20% to 25% of NSCLCs have changes in the KRAS gene that cause them to make an abnormal KRAS protein, which helps the cancer cells grow and spread. NSCLCs with this mutation are often adenocarcinomas, resistant to other drugs such as EGFR inhibitors, and are most often found in people with a smoking history.
• EGFR is a protein that appears in high amounts on the surface of 10% to 20% of NSCLC cells and helps them grow. Some drugs that target EGFR can be used to treat NSCLC with changes in the EGFR gene, which are more common in certain groups, such as those who don’t smoke, women, and Asians. But these drugs don’t seem to be as helpful in patients whose cancer cells have changes in the KRAS gene.
• About 5% of NSCLCs have a change in the ALK gene. This change is most often seen in people who don’t smoke (or who smoke lightly) and have the adenocarcinoma subtype of NSCLC. Doctors may test cancers for changes in the ALK gene to see if drugs that target this change may help them.
• About 1% to 2% of NSCLCs have a rearrangement in the ROS1 gene, which might make the tumor respond to certain targeted drugs.
• A small percentage of NSCLCs have changes in the RET gene. Certain drugs that target cells with RET gene changes might be options for treating these tumors.
• About 5% of NSCLCs have changes in the BRAF gene. Certain drugs that target cells with BRAF gene changes might be an option for treating these tumors.
• A small percentage of NSCLCs have certain changes in the MET gene that make them more likely to respond to some targeted drugs.
• In a small percentage of NSCLCs, the cancer cells have certain changes in the HER2 gene that make them more likely to respond to a targeted drug.
• A small number of NSCLCs have changes in one of the NTRK genes that make them more likely to respond to some targeted drugs.

These genetic tests can be done on tissue taken during a biopsy or surgery for lung cancer. If the biopsy sample is too small and all the studies cannot be done, the testing may also be done on blood that is taken from a vein just like a regular blood draw. This blood contains the DNA from dead tumor cells found in the bloodstream of people with advanced lung cancer. Obtaining the tumor DNA through a blood draw is called a liquid biopsy. Liquid biopsies are done in cases where a tissue biopsy is not possible or if a tissue biopsy is felt to be too dangerous for the patient.

PD-L1 testing on tumor cells

Patients diagnosed with non-small cell lung carcinoma (NSCLC) will have the lung tumor cells tested for PD-L1. PD-L1 is a protein (program death ligand 1) on cancer cells. A score is calculated depending on “if” and “how much” PD-L1 protein the tumor is making. This score will guide decisions about whether the patient would benefit from certain immunotherapy drugs.

Tests before lung surgery

If your doctor thinks the cancer can be treated with surgery, you might need certain tests:

• Pulmonary function tests (PFTs) to see if you would still have enough healthy lung tissue left after surgery
• An EKG (recording of your heart’s electrical activity) and an echocardiogram (ultrasound of your heart) to check the function of your heart  
• Lab work to check other organs to be sure you’re healthy enough for surgery

Your doctor will also want to check if the cancer has already spread to the lymph nodes around the lungs. This is often done before surgery with mediastinoscopy or another technique.

Types of lung surgery

Surgery for lung cancer usually involves removing all or part of a lung. This is called lung resection. There are different types of lung resection:

• Pneumonectomy: This surgery removes an entire lung. This might be needed if the tumor is close to the center of the chest.
• Lobectomy: The lungs are made up of 5 lobes (3 on the right lung and 2 on the left lung). In this surgery, the entire lobe containing the tumor(s) is removed. If it can be done, this is often the preferred type of operation for NSCLC.
• Segmentectomy or wedge resection: In these surgeries, only part of a lobe is removed. This approach might be used if a person doesn’t have enough normal lung function to withstand removing the whole lobe.
• Sleeve resection: This operation may be used to treat some cancers in large airways in the lungs. If you think of the large airway with a tumor as similar to the sleeve of a shirt with a stain a few inches above the wrist, the sleeve resection would be like cutting across the sleeve (airway) above and below the stain (tumor) and then sewing the cuff back onto the shortened sleeve. A surgeon may be able to do this operation instead of a pneumonectomy to preserve more lung function.

The type of operation you have depends on the size and location of the tumor and on how well your lungs are functioning. Doctors often prefer to do a more extensive operation (for example, a lobectomy instead of a segmentectomy) if a person’s lungs are healthy enough, as it may provide a better chance to cure the cancer.

Ways to do lung surgery

There are 2 main ways to do lung surgery: open lung surgery (thoracotomy) and minimally invasive surgery. Minimally invasive surgery includes mainly 2 types: video-assisted thoracoscopic surgery (VATS) and robotic-assisted thoracoscopic surgery (RATS). With any of these surgeries, the goal could be to diagnose (to get more tissue for diagnosis), stage (to look at nearby lymph nodes for possible spread of cancer), and/or treat lung cancer (to remove all known cancer in the lung). All surgeries require general anesthesia, which puts you in a deep sleep.

Open lung surgery (thoracotomy)

In a thoracotomy, the surgeon makes a large cut between the ribs. Where the cut is depends on which part of the lung needs to be removed. In general, the surgeon will spread the ribs to see the lung and nearby organs inside. 

Video-assisted thoracic surgery (VATS)

Video-assisted thoracoscopic surgery (VATS)is a procedure being used more frequently to treat early-stage lung cancers. It uses smaller incisions, typically has a shorter hospital stay and fewer complications than a thoracotomy.

Many experts recommend that only early-stage tumors of the lung be treated this way. The cure rate after this surgery seems to be the same as surgery done with a larger incision. But the surgeon doing this procedure must be experienced, because it requires a great deal of skill.

Robotic-assisted thoracic surgery (RATS)

In this approach, the thoracoscopy is done using a robotic system. The surgeon sits at a control panel in the operating room and moves robotic arms to operate through several small incisions in the patient’s chest.

RATS is similar to VATS in terms of less pain, less blood loss, and shorter recovery time.

For the surgeon, the robotic system may provide more maneuverability and more precision when moving the instruments than standard VATS. Still, the most important factor in the success of either type of thoracoscopic surgery is the surgeon’s experience and skill.

Intraoperative imaging

Along with the results of imaging tests (such as CT scans) done before surgery, surgeons also rely on what they can see and feel during the operation to help determine which parts of the lung need to be removed. However, some lung tumors might not be easily seen or felt, so in some situations it’s possible that a tumor (or parts of tumor) might be missed.

Your surgeon might use a special intraoperative imaging system during the surgery to help find tumors that aren’t easily seen or felt. For this approach, a fluorescent drug called pafolacianine (Cytalux) is injected into your blood within 24 hours before your surgery. The drug travels through your body and attaches to a specific protein found on lung cancer cells. Once in the operating room, the imaging system gives off near-infrared light that causes the drug to light up, which can help the surgeon see which areas of the lung need to be removed.

The most common side effects after getting pafolocianine are nausea, vomiting, belly pain, heartburn, chest pain, itching, and flushing. Your doctor will probably ask you to avoid any supplements that have folic acid in them for a few days before the procedure because they might affect how well this drug works.

Possible risks and side effects of lung surgery

Surgery for lung cancer is a major operation and can have serious side effects, which is why it isn’t a good idea for everyone. All surgery carries some risks that depend to some degree on the extent of the surgery and the person’s overall health.

Possible complications during and soon after surgery can include reactions to anesthesia, excess bleeding, blood clots in the legs or lungs, wound infections, and pneumonia. Rarely, some people may not survive the surgery.

Recovering from lung cancer surgery typically takes weeks to months. If the surgery is done through a thoracotomy (a long incision in the chest), the surgeon must spread ribs to get to the lung, so the area near the incision will hurt for some time after surgery. Your activity might be limited for at least a month or two. People who have VATS instead of thoracotomy tend to have less pain after surgery and to recover more quickly.

If your lungs are in good condition (other than the presence of the cancer), you can usually return to normal activities after some time if a lobe or even an entire lung has been removed. If you also have another lung disease, such as emphysema or chronic bronchitis (which are common among people who have smoked for a long time), you might become short of breath with certain levels of activity after surgery.

After surgery

When you wake up from surgery, you may have a tube (or tubes) coming out of your chest and attached to a special container to allow excess fluid and air to drain out. The tube(s) will be removed once the fluid drainage and air leak slow down enough. Generally, you will need to spend 1 to 7 days in the hospital depending on the type of surgery.