The incidence of lung cancer is strongly correlated with cigarette smoking, with about 90% of lung cancers arising as a result of tobacco use. The risk of lung cancer increases with the number of cigarettes smoked and the time over which smoking has occurred; doctors refer to this risk in terms of pack-years of smoking history (the number of packs of cigarettes smoked per day multiplied by the number of years smoked). For example, a person who has smoked two packs of cigarettes per day for 10 years has a 20 pack-year smoking history. While the risk of lung cancer is increased with even a 10-pack-year smoking history, those with 30-pack-year histories or more are considered to have the greatest risk for the development of lung cancer. Among those who smoke two or more packs of cigarettes per day, one in seven will die of lung cancer.
Pipe and cigar smoking also can cause lung cancer, although the risk is not as high as with cigarette smoking. Thus, while someone who smokes one pack of cigarettes per day has a risk for the development of lung cancer that is 25 times higher than a nonsmoker, pipe and cigar smokers have a risk of lung cancer that is about five times that of a nonsmoker.
Tobacco smoke contains over 4,000 chemical compounds, many of which have been shown to be cancer-causing or carcinogenic. The two primary carcinogens in tobacco smoke are chemicals known as nitrosamines and polycyclic aromatic hydrocarbons. The risk of developing lung cancer decreases each year following smoking cessation as normal cells grow and replace damaged cells in the lung. In former smokers, the risk of developing lung cancer begins to approach that of a nonsmoker about 15 years after cessation of smoking.
Passive smoking or the inhalation of tobacco smoke by nonsmokers who share living or working quarters with smokers, also is an established risk factor for the development of lung cancer. Research has shown that nonsmokers who reside with a smoker have a 24% increase in risk for developing lung cancer when compared with nonsmokers who do not reside with a smoker. The risk appears to increase with the degree of exposure (number of years exposed and number of cigarettes smoked by the household partner) to secondhand smoke.
Exposure to asbestos fibers
Asbestos fibers are silicate fibers that can persist for a lifetime in lung tissue following exposure to asbestos. The workplace was a common source of exposure to asbestos fibers, as asbestos was widely used in the past as both thermal and acoustic insulation. Today, asbestos use is limited or banned in many countries, including the U.S. Both lung cancer and mesothelioma (cancer of the pleura of the lung as well as of the lining of the abdominal cavity called the peritoneum) are associated with exposure to asbestos. Cigarette smoking drastically increases the chance of developing an asbestos-related lung cancer in workers exposed to asbestos; asbestos workers who do not smoke have a fivefold greater risk of developing lung cancer than nonsmokers, but asbestos workers who smoke have a risk that is fifty- to ninety-fold greater than nonsmokers.
Exposure to radon gas
Radon gas is a natural radioactive gas that is a natural decay product of uranium that emits a type of ionizing radiation. As with asbestos exposure, concomitant smoking greatly increases the risk of lung cancer with radon exposure. Radon gas can travel up through soil and enter homes through gaps in the foundation, pipes, drains, or other openings.
While the majority of lung cancers are associated with tobacco smoking, the fact that not all smokers eventually develop lung cancer suggests that other factors, such as individual genetic susceptibility, may play a role in the causation of lung cancer. Numerous studies have shown that lung cancer is more likely to occur in both smoking and nonsmoking relatives of those who have had lung cancer than in the general population. It is unclear how much of this risk is due to shared environmental factors (like a smoking household) and how much is related to genetic risk. People who inherit certain genes, like genes that interfere with DNA repair, may be at greater risk for several types of cancer. Tests to identify people at increased genetic risk of lung cancer are not yet available for routine use.
The presence of certain diseases of the lung, notably chronic obstructive pulmonary disease (COPD), is associated with an increased risk (four- to six-fold the risk of a nonsmoker) for the development of lung cancer even after the effects of concomitant cigarette smoking are excluded. Pulmonary fibrosis (scarring of the lung) appears to increase the risk about seven-fold, and this risk does not appear to be related to smoking.
Prior history of lung cancer
Survivors of lung cancer have a greater risk of developing a second lung cancer than the general population has of developing a first lung cancer. Survivors of non-small cell lung cancers (NSCLCs, see below) have an additive risk of 1%-2% per year for developing a second lung cancer. In survivors of small cell lung cancers (SCLCs, see below), the risk for development of second lung cancers approaches 6% per year.
Air pollution from vehicles, industry, and power plants can raise the likelihood of developing lung cancer in exposed individuals. Up to 1%-2% of lung cancer deaths are attributable to breathing polluted air, and experts believe that prolonged exposure to highly polluted air can carry a risk for the development of lung cancer similar to that of passive smoking.
Exposure to diesel exhaust
Exhaust from diesel engines is made up of gases and soot (particulate matter). Many occupations, such as truck drivers, toll booth workers, forklift and other heavy machinery operators, railroad and dock workers, miners, garage workers and mechanics, and some farm workers are frequently exposed to diesel exhaust. Studies of workers exposed to diesel exhaust have shown a small but significant increase in the risk of developing lung cancer.
Current research suggests that if a member of your immediate family, such as your parent or sibling, has or had lung cancer, you may have a slightly higher risk of developing the disease. This is also the case if you have multiple family members who’ve had lung cancer.
This is true even if you don’t smoke. At this point, it’s unclear whether genetics cause lung cancer or merely increase your chances of developing it.
According to the Lung Cancer Alliance (LCA), the average age in the United States for a lung cancer diagnosis is around 70. Only about 10 percent of lung cancers occur in people younger than 50. The older you are, the longer you’ve been exposed to harmful chemicals. This increases your risk of cancer.
Past lung disease
If you have a history of chronic illnesses that affect the lungs, you may be at a greater risk of developing lung cancer. Lung diseases can cause inflammation and scarring in the lungs. These include tuberculosis and chronic obstructive pulmonary disease, which includes chronic bronchitis and emphysema.
Radiation therapy to the chest
Radiation therapy for treating other cancers may increase your risk of lung cancer. This risk is higher if you smoke.
You’re at risk for lung cancer if you don’t smoke but you’re exposed to cigarette smoke regularly in your daily environment, such as:
According to the LCA, secondhand smoke increases your risk of lung cancer by 20 to 30 percent.
Although nonsmokers can get lung cancer, smoking tobacco, such as by using cigarettes, cigars, and pipes, is the top risk factor for lung cancer. According to the Centers for Disease Control and Prevention (CDC), about 90 percent of all lung cancer deaths in the United States are due to smoking. Tobacco and tobacco smoke contain 7,000 chemicals, many of which are carcinogenic. Inhaling the chemicals in a cigarette immediately triggers a change in lung tissue. Initially, your body is able to repair the damage. Its ability to do so decreases as exposure continues. The more frequently you smoke and the longer you smoke, the greater your chances of developing lung cancer.
You may have an increased risk for lung cancer if you don’t eat a diverse mix of healthy foods like fruits and vegetables. This is especially true if you’re a smoker.
Exposure to certain toxins in the environment can increase your risk of developing lung cancer. These toxins include radon, asbestos, and other chemicals.
Radon is an odorless, colorless, and tasteless gas that occurs naturally with the breakdown of uranium in rocks and soil. These gases can seep into building foundations and into living and working spaces. Because radon is difficult to detect, you could have exposure to it without knowing it. People who smoke have an increased risk from the effects of radon than those who don’t smoke. According to the LCA, radon is the second leading cause of lung cancer in the United States.
Asbestos is an industrial material that people use in construction for insulation and as a fire retardant. When the material is disturbed, small fibers become airborne and can be inhaled. You’re at an increased risk of developing lung cancer if you’re exposed to asbestos on a regular basis.
Other chemical exposures can raise your lung cancer risks. Some examples of these chemicals are:
Symptoms of lung cancer are varied depending upon where and how widespread the tumor is. Warning signs of lung cancer are not always present or easy to identify. Lung cancer may not cause pain or other symptoms in some cases. A person with lung cancer may have the following kinds of symptoms:
Doctors use a wide range of diagnostic procedures and tests to diagnose lung cancer. These include the following:
Bone scans are used to create images of bones on a computer screen or on film. Doctors may order a bone scan to determine whether a lung cancer has metastasized to the bones. In a bone scan, a small amount of radioactive material is injected into the bloodstream and collects in the bones, especially in abnormal areas such as those involved by metastatic tumors. The radioactive material is detected by a scanner, and the image of the bones is recorded on a special film for permanent viewing.
Sputum cytology: The diagnosis of lung cancer always requires confirmation of malignant cells by a pathologist, even when symptoms and X-ray studies are suspicious for lung cancer. The simplest method to establish the diagnosis is the examination of sputum under a microscope. If a tumor is centrally located and has invaded the airways, this procedure, known as a sputum cytology examination, may allow visualization of tumor cells for diagnosis. This is the most risk-free and inexpensive tissue diagnostic procedure, but its value is limited since tumor cells will not always be present in sputum even if a cancer is present. Also, noncancerous cells may occasionally undergo changes in reaction to inflammation or injury that makes them look like cancer cells.
Bronchoscopy: Examination of the airways by bronchoscopy (visualizing the airways through a thin, fiberoptic probe inserted through the nose or mouth) may reveal areas of tumor that can be sampled (biopsied) for diagnosis by a pathologist. A tumor in the central areas of the lung or arising from the larger airways is accessible to sampling using this technique. Bronchoscopy may be performed using a rigid or a flexible fiberoptic bronchoscope and can be performed in a same-day outpatient bronchoscopy suite, an operating room, or on a hospital ward. The procedure can be uncomfortable, and it requires sedation or anesthesia. While bronchoscopy is relatively safe, it must be carried out by a lung specialist (pulmonologist or surgeon) experienced in the procedure. When a tumor is visualized and adequately sampled, an accurate cancer diagnosis usually is possible. Some patients may cough up dark-brown blood for one to two days after the procedure. More serious but rare complications include a greater amount of bleeding, decreased levels of oxygen in the blood, and heart arrhythmias as well as complications from sedative medications and anesthesia.
Needle biopsy: Fine-needle aspiration (FNA) through the skin, most commonly performed with radiological imaging for guidance, may be useful in retrieving cells for diagnosis from tumor nodules in the lungs. Needle biopsies are particularly useful when the lung tumor is peripherally located in the lung and not accessible to sampling by bronchoscopy. A small amount of local anesthetic is given prior to insertion of a thin needle through the chest wall into the abnormal area in the lung. Cells are suctioned into the syringe and are examined under the microscope for tumor cells. This procedure is generally accurate when the tissue from the affected area is adequately sampled, but in some cases, adjacent or uninvolved areas of the lung may be mistakenly sampled. A small risk (3%-5%) of an air leak from the lungs (called a pneumothorax, which can easily be treated) accompanies the procedure.
Thoracentesis: Sometimes lung cancers involve the lining tissue of the lungs (pleura) and lead to an accumulation of fluid in the space between the lungs and chest wall (called a pleural effusion). Aspiration of a sample of this fluid with a thin needle (thoracentesis) may reveal the cancer cells and establish the diagnosis. As with the needle biopsy, a small risk of a pneumothorax is associated with this procedure.
Major surgical procedures: If none of the aforementioned methods yields a diagnosis, surgical methods must be employed to obtain tumor tissue for diagnosis. These can include mediastinoscopy (examining the chest cavity between the lungs through a surgically inserted probe with biopsy of tumor masses or lymph nodes that may contain metastases) or thoracotomy (surgical opening of the chest wall for removal or biopsy of a tumor). With a thoracotomy, it is rare to be able to completely remove a lung cancer, and both mediastinoscopy and thoracotomy carry the risks of major surgical procedures (complications such as bleeding, infection, and risks from anesthesia and medications). These procedures are performed in an operating room, and the patient must be hospitalized.
Blood tests: While routine blood tests alone cannot diagnose lung cancer, they may reveal biochemical or metabolic abnormalities in the body that accompany cancer. For example, elevated levels of calcium or of the enzyme alkaline phosphatase may accompany cancer that is metastatic to the bones. Likewise, elevated levels of certain enzymes normally present within liver cells, including aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT), signal liver damage, possibly through the presence of tumor metastatic to the liver. One current focus of research in the area of lung cancer is the development of a blood test to aid in the diagnosis of lung cancer. Researchers have preliminary data that has identified specific proteins, or biomarkers, that are in the blood and may signal that lung cancer is present in someone with a suspicious area seen on a chest X-ray or other imaging study.
Molecular testing: For advanced NSCLCs, molecular genetic testing is carried out to look for genetic mutations in the tumor. Mutations that are responsible for tumor growth are known as driver mutations. For example, testing may be done to look for mutations or abnormalities in the epithelial growth factor receptor (EGFR) and the anaplastic lymphoma kinase (ALK) genes. Other genes that may be mutated include MAPK and PIK3. Specific therapies are available that may be administered to patients whose tumors have these alterations in their genes.
The treatment of lung cancer requires a team approach. Surgical oncologists are surgeons specialized in the removal of cancers. Thoracic surgeons or general surgeons may also surgically treat lung cancers. Medical and radiation oncologists are specialists in the treatment of cancers with medications and radiation therapy, respectively. Other specialists who may be involved in the care of people with lung cancer include pain and palliative care specialists, as well as pulmonary specialists (medical pulmonologists).
Treatment for lung cancer primarily involves surgical removal of the cancer, chemotherapy, or radiation therapy, as well as combinations of these treatments. Targeted therapies and immunotherapy are becoming more common, as well. The decision about which treatments will be appropriate for a given individual must take into account the location and extent of the tumor, as well as the overall health status of the patient.
As with other cancers, therapy may be prescribed that is intended to be curative (removal or eradication of a cancer) or palliative (measures that are unable to cure a cancer but can reduce pain and suffering). More than one type of therapy may be prescribed. In such cases, the therapy that is added to enhance the effects of the primary therapy is referred to as adjuvant therapy. An example of adjuvant therapy is chemotherapy or radiotherapy administered after surgical removal of a tumor in an attempt to kill any tumor cells that remain following surgery.
Surgery: Surgical removal of the tumor is generally performed for limited-stage (stage I or sometimes stage II) NSCLC and is the treatment of choice for cancer that has not spread beyond the lung. About 10%-35% of lung cancers can be removed surgically, but removal does not always result in a cure, since the tumors may already have spread and can recur at a later time. Among people who have an isolated, slow-growing lung cancer removed, 25%-40% are still alive five years after diagnosis. It is important to note that although a tumor may be anatomically suitable for resection, surgery may not be possible if the person has other serious conditions (such as severe heart or lung disease) that would limit their ability to survive an operation. Surgery is less often performed with SCLC than with NSCLC because these tumors are less likely to be localized to one area that can be removed.
The surgical procedure chosen depends upon the size and location of the tumor. Surgeons must open the chest wall and may perform a wedge resection of the lung (removal of a portion of one lobe), a lobectomy (removal of one lobe), or a pneumonectomy (removal of an entire lung). Sometimes lymph nodes in the region of the lungs also are removed (lymphadenectomy). Surgery for lung cancer is a major surgical procedure that requires general anesthesia, hospitalization, and follow-up care for weeks to months. Following the surgical procedure, patients may experience difficulty breathing, shortness of breath, pain, and weakness. The risks of surgery include complications due to bleeding, infection, and complications of general anesthesia.
Radiation: Radiation therapy may be employed as a treatment for both NSCLC and SCLC. Radiation therapy uses high-energy X-rays or other types of radiation to kill dividing cancer cells. Radiation therapy may be given as curative therapy, palliative therapy (using lower doses of radiation than with curative therapy), or as adjuvant therapy in combination with surgery or chemotherapy. The radiation is either delivered externally, by using a machine that directs radiation toward the cancer, or internally through placement of radioactive substances in sealed containers within the area of the body where the tumor is localized. Brachytherapy is a term used to describe the use of a small pellet of radioactive material placed directly into the cancer or into the airway next to the cancer. This is usually done through a bronchoscope.
Radiation therapy can be given if a person refuses surgery, if a tumor has spread to areas such as the lymph nodes or trachea making surgical removal impossible, or if a person has other conditions that make them too ill to undergo major surgery. Radiation therapy generally only shrinks a tumor or limits its growth when given as a sole therapy, yet in 10%-15% of people it leads to long-term remission and palliation of the cancer. Combining radiation therapy with chemotherapy can further prolong survival when chemotherapy is administered. A person who has severe lung disease in addition to a lung cancer may not be able to receive radiotherapy to the lung since the radiation can further decrease function of the lungs. A type of external radiation therapy called the "gamma knife" is sometimes used to treat single brain metastases. In this procedure, multiple beams of radiation coming from different directions are focused on the tumor over a few minutes to hours while the head is held in place by a rigid frame. This reduces the dose of radiation that is received by noncancerous tissues.
For external radiation therapy, a process called simulation is necessary prior to treatment. Using CT scans, computers, and precise measurements, simulation maps out the exact location where the radiation will be delivered, called the treatment field or port. This process usually takes 30 minutes to two hours. The external radiation treatment itself generally is done four or five days a week for several weeks.
SCLC often spreads to the brain. Sometimes people with SCLC that is responding well to treatment are treated with radiation therapy to the head to treat very early spread to the brain (called micrometastasis) that is not yet detectable with CT or MRI scans and has not yet produced symptoms. This is known as prophylactic brain radiation. Brain radiation therapy can cause short-term memory problems, fatigue, nausea, and other side effects.
Radiation therapy does not carry the risks of major surgery, but it can have unpleasant side effects, including fatigue and lack of energy. A reduced white blood cell count (rendering a person more susceptible to infection) and low blood platelet levels (making blood clotting more difficult and resulting in excessive bleeding) also can occur with radiation therapy. If the digestive organs are in the field exposed to radiation, patients may experience nausea, vomiting, or diarrhea. Radiation therapy can irritate the skin in the area that is treated, but this irritation generally improves with time after treatment has ended.
Chemotherapy: Both NSCLC and SCLC may be treated with chemotherapy. Chemotherapy refers to the administration of drugs that stop the growth of cancer cells by killing them or preventing them from dividing. Chemotherapy may be given alone, as an adjuvant to surgical therapy, or in combination with radiotherapy. While a number of chemotherapeutic drugs have been developed, the class of drugs known as the platinum-based drugs have been the most effective in treatment of lung cancers.
Chemotherapy is the treatment of choice for most SCLC, since these tumors are generally widespread in the body when they are diagnosed. Only half of people who have SCLC survive for four months without chemotherapy. With chemotherapy, their survival time is increased up to four- to fivefold. Chemotherapy alone is not particularly effective in treating NSCLC, but when NSCLC has metastasized, it can prolong survival in many cases.
Chemotherapy may be given as pills, as an intravenous infusion, or as a combination of the two. Chemotherapy treatments usually are given in an outpatient setting. A combination of drugs is given in a series of treatments, called cycles, over a period of weeks to months, with breaks in between cycles. Unfortunately, the drugs used in chemotherapy also kill normally dividing cells in the body, resulting in unpleasant side effects. Damage to blood cells can result in increased susceptibility to infections and difficulties with blood clotting (bleeding or bruising easily). Other side effects include fatigue, weight loss, hair loss, nausea, vomiting, diarrhea, and mouth sores. The side effects of chemotherapy vary according to the dosage and combination of drugs used and may also vary from individual to individual. Medications have been developed that can treat or prevent many of the side effects of chemotherapy. The side effects generally disappear during the recovery phase of the treatment or after its completion.
Targeted therapy: Molecularly targeted therapy involves the administration of drugs that have been identified to work in subsets of patients whose tumors have specific genetic changes (driver mutations) that promote tumor growth.
EGFR-targeted therapies: The drugs erlotinib (Tarceva), afatinib (Gilotrif), and gefitinib (Iressa) are so-called targeted drugs that more specifically target cancer cells, resulting in less damage to normal cells than general chemotherapeutic agents. Erlotinib, gefitinib, and afatinib target a protein called the epidermal growth factor receptor (EGFR) that is important in promoting the division of cells. The gene encoding this protein is mutated in many cases of non-small cell lung cancer, creating a mutation that encourages tumor growth. Mutations in the EGFR gene are more common in cancers in women and in people who have never smoked. Drugs that target the EGFR receptor sometimes stop working after a time, which is known as resistance to the drug. Resistance often occurs because the cancer has developed a new mutation in the same gene, and a common example of this is the so-called EGFR T790M mutation. Some newer EGFR-targeted drugs also work against cells with the T790M mutation, including osimertinib (Tagrisso). Necitumumab (Portrazza) is another drug that targets EGFR. It can be used along with chemotherapy as the first treatment in people with advanced NSCLC of the squamous cell type.
Other targeted therapies: Other targeted drugs are available that target other driver mutations. These other targeted therapies include the ALK tyrosine kinase inhibitor drugs crizotinib (Xalkori), alectinib (Alecensa), brigatinib (Alunbrig), and ceritinib (Zykadia) that are used in patients whose tumors have an abnormality of the ALK gene as the driver mutation. Some of these drugs may also be helpful for people whose cancers have an abnormality of the gene known as ROS1.
The gene known as BRAF can also be abnormal in lung cancers causing the production of BRAF protein that promotes the cancer's growth. Dabrafenib (Tafinlar) is a type of drug known as a BRAF inhibitor and attacks the BRAF protein directly. Trametinib (Mekinist) is known as a MEK inhibitor because it attacks MEK proteins, which are related to BRAF proteins. These may be used for patients with tumors that have abnormal BRAF genes.
Other attempts at targeted therapy include drugs known as antiangiogenesis drugs, which block the development of new blood vessels within a cancer. Without adequate blood vessels to supply oxygen-carrying blood, the cancer cells will die. The antiangiogenic drug bevacizumab (Avastin) has also been found to prolong survival in advanced lung cancer when it is added to the standard chemotherapy regimen. Bevacizumab is given intravenously every two to three weeks. However, since this drug may cause bleeding, it is not appropriate for use in patients who are coughing up blood, if the lung cancer has spread to the brain, or in people who are receiving anticoagulation therapy ("blood thinner" medications). Bevacizumab also is not used in cases of squamous cell cancer because it leads to bleeding from this type of lung cancer. Ramucirumab (Cyramza) is another angiogenesis inhibitor that can be used to treat advanced non-small cell lung cancer.
Immunotherapy: Immunotherapy may be an effective option for some patients with advanced lung cancers. Immunotherapy drugs work by strengthening the activity of the immune system against tumor cells. The immunotherapy drugs nivolumab (Opdivo) and pembrolizumab (Keytruda) were approved by the U.S. FDA in 2015 for the treatment of lung cancer. These drugs are checkpoint inhibitors that target checkpoints or areas that control the immune response and promote the immune response. These two drugs target the PD-1 protein, which strengthens the immune response against the cancers. Atezolizumab (Tecentriq) is a drug that targets PD-L1, a protein related to PD-1 that is found on some tumor cells and immune cells.
Radiofrequency ablation (RFA): Radiofrequency ablation is being studied as an alternative to surgery, particularly in cases of early stage lung cancer. In this type of treatment, a needle is inserted through the skin into the cancer, usually under guidance by CT scanning. Radiofrequency (electrical) energy is then transmitted to the tip of the needle where it produces heat in the tissues, killing the cancerous tissue and closing small blood vessels that supply the cancer. RFA usually is not painful and has been approved by the FDA for the treatment of certain cancers, including lung cancers. Studies have shown that this treatment can prolong survival similarly to surgery when used to treat early stages of lung cancer but without the risks of major surgery and the prolonged recovery time associated with major surgical procedures.
Experimental therapies: Since no therapy is currently available that is absolutely effective in treating lung cancer, patients may be offered a number of new therapies that are still in the experimental stage, meaning that doctors do not yet have enough information to decide whether these therapies should become accepted forms of treatment for lung cancer. New drugs or new combinations of drugs are tested in so-called clinical trials, which are studies that evaluate the effectiveness of new medications in comparison with those treatments already in widespread use. Newer types of immunotherapy are being studied that involve the use of vaccine-related therapies that attempt to utilize the body's immune system to directly fight cancer cells. Lung cancer treatment vaccines are being studied in clinical trials.
Cessation of smoking and eliminating exposure to tobacco smoke is the most important measure that can prevent lung cancer. Many products, such as nicotine gum, nicotine sprays, or nicotine inhalers, may be helpful to people trying to quit smoking. Minimizing exposure to passive smoking also is an effective preventive measure. Using a home radon test kit can identify and allow correction of increased radon levels in the home. Methods that allow early detection of cancers, such as the helical low-dose CT scan, also may be of value in the identification of small cancers that can be cured by surgical resection and prevented from becoming widespread, incurable, metastatic cancer.