Lung cancer, also known as carcinoma of the lung or pulmonary carcinoma, is a malignant lung tumor characterized by uncontrolled cell growth in tissues of the lung.
If left untreated, this growth can spread beyond the lung by process of metastasis into nearby tissue or other parts of the body. Most cancers that start in the lung, known as primary lung cancers, are carcinomas that derive from epithelial cells. The main primary types are small-cell lung carcinoma (SCLC) and non-small-cell lung carcinoma (NSCLC). The most common symptoms are coughing (including coughing up blood), weight loss, shortness of breath, and chest pains.
The vast majority (80–90%) of cases of lung cancer are due to long-term exposure to tobacco smoke. About 10–15% of cases occur in people who have never smoked. These cases are often caused by a combination of genetic factors and exposure to radon gas, asbestos, or other forms of air pollution, including second-hand smoke. Lung cancer may be seen on chest radiographs and computed tomography (CT) scans. The diagnosis is confirmed by biopsy which is usually performed by bronchoscopy or CT-guidance.
Treatment and long-term outcomes depend on the type of cancer, the stage (degree of spread), and the person’s overall health, measured by performance status. Common treatments include surgery, chemotherapy, and radiotherapy. NSCLC is sometimes treated with surgery, whereas SCLC usually responds better to chemotherapy and radiotherapy. Overall, 16.8% of people in the United States diagnosed with lung cancer survive five years after the diagnosis, while outcomes on average are worse in the developing world. Worldwide, lung cancer is the most common cause of cancer-related death in men and women, and was responsible for 1.56 million deaths annually, as of 2012.
Signs and symptoms
Signs and symptoms which may suggest lung cancer include:
- Respiratory symptoms: coughing, coughing up blood, wheezing or shortness of breath
- Systemic symptoms: weight loss, fever, clubbing of the fingernails, or fatigue
- Symptoms due to the cancer mass pressing on adjacent structures: chest pain, bone pain, superior vena cava obstruction, difficulty swallowing
If the cancer grows in the airways, it may obstruct airflow, causing breathing difficulties. The obstruction can lead to accumulation of secretions behind the blockage, and predispose to pneumonia.
Depending on the type of tumor, paraneoplastic phenomena—symptoms not due to the local presence of cancer—may initially attract attention to the diseases. In lung cancer, these phenomena may include Lambert–Eaton myasthenic syndrome (muscle weakness due to autoantibodies), hypercalcemia, or syndrome of inappropriate antidiuretic hormone (SIADH, abnormally concentrated urine and diluted blood). Tumors in the top of the lung, known as Pancoast tumors, may invade the local part of the sympathetic nervous system, leading to Horner’s syndrome (dropping of the eyelid and a small pupil on that side), as well as damage to the brachial plexus.
Many of the symptoms of lung cancer (poor appetite, weight loss, fever, fatigue) are not specific. In many people, the cancer has already spread beyond the original site by the time they have symptoms and seek medical attention. Symptoms that suggest the presence of metastatic disease include weight loss, bone pain and neurological symptoms (headaches, fainting, convulsions, or limb weakness). Common sites of spread include the brain, bone, adrenal glands, opposite lung, liver, pericardium, and kidneys. About 10% of people with lung cancer do not have symptoms at diagnosis; these cancers are incidentally found on routine chest radiography.
Cancer develops following genetic damage to DNA and epigenetic changes. These changes affect the normal functions of the cell, including cell proliferation, programmed cell death (apoptosis) and DNA repair. As more damage accumulates, the risk of cancer increases.
Smoking, particularly of cigarettes, is by far the main contributor to lung cancer. Cigarette smoke contains at least 73 known carcinogens, including benzo[a]pyrene, NNK, 1,3-butadiene and the radioisotope polonium-210. Across the developed world, 90% of lung cancer deaths in men during the year 2000 were attributed to smoking (70% for women). Smoking accounts for 80–90% of lung cancer cases.
Passive smoking—the inhalation of smoke from another’s smoking—is a cause of lung cancer in nonsmokers. A passive smoker can be defined as someone living or working with a smoker. Studies from the US, Europe and the UK have consistently shown a significantly increased risk among those exposed to passive smoke. Those who live with someone who smokes have a 20–30% increase in risk while those who work in an environment with second hand smoke have a 16–19% increase in risk. Investigations of side-stream smoke suggest it is more dangerous than direct smoke. Passive smoking causes about 3,400 deaths from lung cancer each year in the USA.
Marijuana smoke contains many of the same carcinogens as those in tobacco smoke. However the effect of smoking cannabis on lung cancer risk is not clear. A 2013 review did not find an increased risk from light to moderate use. A 2014 review found that smoking cannabis doubled the risk of lung cancer.
Radon is a colourless and odorless gas generated by the breakdown of radioactive radium, which in turn is the decay product of uranium, found in the Earth’s crust. The radiation decay products ionize genetic material, causing mutations that sometimes turn cancerous. Radon is the second-most common cause of lung cancer in the USA, causing about 21,000 deaths each year. The risk increases 8–16% for every 100 Bq/m³ increase in the radon concentration. Radon gas levels vary by locality and the composition of the underlying soil and rocks. About one in 15 homes in the US has radon levels above the recommended guideline of 4 picocuries per liter (pCi/l) (148 Bq/m³).
Asbestos can cause a variety of lung diseases, including lung cancer. Tobacco smoking and asbestos have a synergistic effect on the formation of lung cancer. In smokers who work with asbestos, the risk of lung cancer is increased 45-fold compared to the general population. Asbestos can also cause cancer of the pleura, called mesothelioma (which is different from lung cancer).
Outdoor air pollution has a small effect on increasing the risk of lung cancer. Fine particulates (PM2.5) and sulfate aerosols, which may be released in traffic exhaust fumes, are associated with slightly increased risk. For nitrogen dioxide, an incremental increase of 10 parts per billion increases the risk of lung cancer by 14%. Outdoor air pollution is estimated to account for 1–2% of lung cancers.
Tentative evidence supports an increased risk of lung cancer from indoor air pollution related to the burning of wood, charcoal, dung or crop residue for cooking and heating. Women who are exposed to indoor coal smoke have about twice the risk and a number of the by-products of burning biomass are known or suspected carcinogens. This risk affects about 2.4 billion people globally, and is believed to account for 1.5% of lung cancer deaths.
About 8% of lung cancer is due to inherited factors. In relatives of people with lung cancer, the risk is increased 2.4 times. This is likely due to a combination of genes. Polymorphisms on chromosomes 5, 6 and 15 are known to affect the risk of lung cancer.
Numerous other substances, occupations, and environmental exposures have been linked to lung cancer. The International Agency for Research on Cancer (IARC) states there is “sufficient evidence” to show the following are carcinogenic in the lungs:
- Some metals (aluminum production, cadmium and cadmium compounds, chromium(VI) compounds, beryllium and beryllium compounds, iron and steel founding, nickel compounds, arsenic and inorganic arsenic compounds, underground hematite mining)
- Some products of combustion (incomplete combustion, coal (indoor emissions from household coal burning), coal gasification, coal-tar pitch, coke production, soot, diesel engine exhaust)
- Ionizing radiation (X-radiation, gamma radiation, plutonium)
- Some toxic gases (methyl ether (technical grade), Bis-(chloromethyl) ether, sulfur mustard, MOPP (vincristine-prednisone-nitrogen mustard-procarbazine mixture), fumes from painting)
- Rubber production and crystalline silica dust
Performing a chest radiograph is one of the first investigative steps if a person reports symptoms that may suggest lung cancer. This may reveal an obvious mass, widening of the mediastinum (suggestive of spread to lymph nodes there), atelectasis (collapse), consolidation (pneumonia) or pleural effusion. CT imaging is typically used to provide more information about the type and extent of disease. Bronchoscopy or CT-guided biopsy is often used to sample the tumor for histopathology.
Lung cancer often appears as a solitary pulmonary nodule on a chest radiograph. However, the differential diagnosis is wide. Many other diseases can also give this appearance, including tuberculosis, fungal infections, metastatic cancer or organizing pneumonia. Less common causes of a solitary pulmonary nodule include hamartomas, bronchogenic cysts, adenomas, arteriovenous malformation, pulmonary sequestration, rheumatoid nodules, granulomatosis with polyangiitis, or lymphoma. Lung cancer can also be an incidental finding, as a solitary pulmonary nodule on a chest radiograph or CT scan done for an unrelated reason. The definitive diagnosis of lung cancer is based on histological examination of the suspicious tissue in the context of the clinical and radiological features.
Clinical practice guidelines recommend frequencies for pulmonary nodule surveillance. CT imaging should not be used for longer or more frequently than indicated as extended surveillance exposes people to increased radiation.
Smoking prevention and smoking cessation are effective ways of preventing the development of lung cancer.
While in most countries industrial and domestic carcinogens have been identified and banned, tobacco smoking is still widespread. Eliminating tobacco smoking is a primary goal in the prevention of lung cancer, and smoking cessation is an important preventive tool in this process.
Policy interventions to decrease passive smoking in public areas such as restaurants and workplaces have become more common in many Western countries. Bhutan has had a complete smoking ban since 2005 while India introduced a ban on smoking in public in October 2008. The World Health Organization has called for governments to institute a total ban on tobacco advertising to prevent young people from taking up smoking. They assess that such bans have reduced tobacco consumption by 16% where instituted.
Cancer screening uses medical tests to detect disease in large groups of people with no symptoms. For individuals with high risk of developing lung cancer, computed tomography (CT) screening can detect cancer and give a person options to respond to it in a way that prolongs life. This form of screening reduces the chance of death from lung cancer by an absolute amount of 0.3% (relative amount of 20%). High risk people are those age 55-74 who have smoked equivalent amount of a pack of cigarettes daily for 30 years including time within the past 15 years.
CT screening is associated with a high rate of falsely positive tests which may result in unneeded treatment. For each true positive scan there are about 19 falsely positives scans. Other concerns include radiation exposure and the cost of testing along with follow up. Research has not found two other available tests—sputum cytology or chest radiograph (CXR) screening tests—to have any benefit.
The U.S. Preventative Services Task Force (USPSTF) recommends yearly screening using low-dose computed tomography in those who have a total smoking history of 30 pack-years and are between 55 to 80 years old until a person has not been smoking for more than 15 years. Screening should not be done in those with other health problems that would make treatment of lung cancer if found not an option. The English National Health Service was in 2014 re-examining the evidence for screening.
Other prevention strategies
The long-term use of supplemental vitamin A, vitamin C, vitamin D or vitamin E does not reduce the risk of lung cancer. Some studies suggest that people who eat diets with a higher proportion of vegetables and fruit tend to have a lower risk, but this may be due to confounding—with the lower risk actually due to the association of a high fruit/vegetables diet with less smoking. More rigorous studies have not demonstrated a clear association between diet and lung cancer risk.
Treatment for lung cancer depends on the cancer’s specific cell type, how far it has spread, and the person’s performance status. Common treatments include Palliative Care, Surgery, Chemotherapy, Acupuncture, Ozone Therapy and Radiation Therapy. Targeted therapy of lung cancer is growing in importance for advanced lung cancer.