Lung Cancer

Risk factors for developing lung cancer include:

• Smoking – at least 80% of lung cancer deaths are thought to be related to smoking. The more a person smokes, and the longer that he or she smokes, the greater the risk. Second-hand smoke also increases risk of lung cancer.
• Radon exposure – a common cause of lung cancer in nonsmokers; it is a colorless, odorless radioactive gas that occurs naturally in soil but can accumulate in some homes.
• Asbestos exposure – this can increase the risk of lung cancer. Asbestos is more commonly associated with mesothelioma, a rare cancer of the lining of the chest and abdomen. Most cases of mesothelioma – about 70% to 80% – arise in people with a history of working with asbestos, especially in the shipbuilding, construction, automotive, and fireproofing industries.
• Exposure to cancer-causing substances (carcinogens) such as arsenic or chromium (often in the workplace)
• Radiation therapy – such as previous treatment for another type of cancer
• Family or personal history of lung cancer

There are two main categories of lung cancer, non-small cell and small cell. These cancers are named and differentiated based upon the size, shape, and characteristics of the tumor cells. In addition, there are several less common types of cancer that can affect the lungs. 

The following table lists the different types of lung cancers.

It is difficult to detect lung cancer at an early stage. There are often no symptoms until the condition is well advanced. Examples of symptoms include:

• Persistent cough
• Persistent or recurrent lung infections (e.g., pneumonia, bronchitis)
• Hoarseness
• Shortness of breath
• Wheezing
• Chest pain
• Fatigue or weakness
• Weight loss
• Loss of appetite
• Coughing up blood

When lung cancer spreads (metastasizes) to other areas of the body, other signs and symptoms related to those sites may develop. Examples include bone pain, neurological symptoms, and swollen lymph nodes.

The goals with testing for lung cancer are to detect it as soon as possible, determine the specific type and how far it has spread, help guide treatment, and evaluate a person's general state of health and lung function.

Screening
There are no blood tests that can be used to screen for or detect lung cancer. However, recent guidelines from the American College of Chest Physicians, American Cancer Society, and National Comprehensive Cancer Network recommend that people who have a significant risk of developing lung cancer due to age and previous or current smoking history be offered periodic low-dose computed tomography (LDCT) scanning to help detect early lung cancer. This recommendation is limited to those at a significant risk, and screening should only be done by facilities that are experienced with the procedure. For information on this type of procedure, visit RadiologyInfo.org: Computed tomography, chest.

Sometimes a chest X-ray may be used to observe the lungs and nearby structures to look for tumors. Likewise, sputum cytology, a method of obtaining cells from the lungs, may be used to look for cancer cells. However, these procedures are not recommended for screening purposes by any established guidelines.

Diagnosis and Staging
A diagnosis of lung cancer is usually confirmed by examining tissue and/or cells from the lungs with a microscope. If the tissue or cells are cancerous, the next step is to determine the stage (or extent) of disease. Treatment will depend in part on the "stage" of the cancer; it is categorized by how far it has spread from its original site. Tests used for diagnosis and staging include:

• Biopsy – when a suspected cancer is found, a biopsy is taken, removing some tissue from the suspicious site for examination under a microscope by a pathologist. A sample of cells may be collected by inserting a small needle into the lungs and aspirating the cells (sometimes called a needle biopsy, fine needle aspiration or FNA). More commonly, a long, thin, lighted tube called a bronchoscope may be inserted into the airways to view the structures and collect a tissue sample. In some cases, a sample of tissue may be collected during a surgical procedure.
• Cytology – this procedure may be used to help establish a diagnosis of lung cancer by examining cells in a sample of fluid collected during a bronchoscope examination or in a sample of sputum. Sputum samples (deep respiratory secretions, not saliva) may be coughed up and expelled into a sterile cup provided by the laboratory. If a person cannot produce a sputum sample, then it can often be induced by inhaling a sterile saline or glycerin aerosol for several minutes to loosen phlegm in the lungs.
• Pleural fluid analysis – this is an evaluation of fluid removed from the space between the lungs and chest wall by a procedure called thoracentesis. It may be used as part of staging to help determine whether cancer has spread to the outside lining of the lungs. This is only done in people who have an increased amount of fluid in this space since normally the amount of fluid present is too small to sample safely.

Staging may also involve other evaluations, such as a physical exam or imaging tests that look for evidence of cancer in other organs or parts of the body.

Guide Treatment
Tests may be performed on tumor tissue to help guide therapy. Some people with non-small cell lung cancer (NSCLC) may be candidates for targeted therapy, depending on the type of NSCLC and results of some molecular tests. Targeted therapy is a newer type of cancer treatment that uses drugs that have a greater effect on cancerous tissue, reducing many of the side effects associated with standard therapy. It is based on the fact that the genetic makeup of the cancer cells is different than the normal cells around them. Targeted therapy aims to disrupt specific steps or processes that are somewhat unique to the growth of cancer cells.

Testing may include:

• EGFR gene mutation – present in 10% to 15% of adenocarcinoma non-small cell lung cancers (see the table of types of lung cancers on the Overview page). If present, a person is more likely to respond to tyrosine kinase inhibitor drug therapies such as gefitinib and erlotinib.
• KRAS gene mutation – includes 20% to 30% of adenocarcinoma non-small cell lung cancers. If present, a person is less likely to respond to tyrosine kinase inhibitors.
• ALK gene mutation / gene rearrangement (EML4-ALK, about 5% of non-small cell lung cancers) – most often seen in light smokers or non-smokers with adenocarcinoma. If a mutation is present, the cancer is more likely to respond to ALK kinase inhibitors such as crizotinib and less likely to respond to tyrosine kinase inhibitors.
• ROS1 gene mutation (1% to 2% of adenocarcinoma non-small cell lung cancers) – those with gene rearrangement are more likely to respond to crizotinib and less likely to respond to tyrosine kinase inhibitors.

Other laboratory tests
General testing is often used to help assess an affected person's health and/or to monitor them during treatment. Some of these tests may include:

• CBC (complete blood count) – to evaluate blood cells
• CMP (comprehensive metabolic panel) – to evaluate organ function
• Blood gases (or ABGs) – a blood sample is collected from an artery to measure blood pH, oxygen and carbon dioxide to evaluate how well the lungs are working
• Sputum culture – used to detect and identify bacterial lung infections

Non-laboratory tests
Pulmonary function tests (PFTs) may be used to help evaluate lung function. For more complete information, visit the web site for Johns Hopkins Medicine: Pulmonary Function Laboratory.

A variety of imaging tests are used to help diagnose and stage lung cancers. They include:

• Chest x-ray
• Computed tomography (CT) scan
• Magnetic resonance imaging (MRI) scan
• Positron emission tomography (PET) scan
• Ultrasound
• Bone scan

For additional details about these procedures, visit RadiologyInfo.org.

Appropriate lung cancer treatment depends upon the type of cancer, its stage, and its characteristics. Staging evaluates the size of the cancer, its location, and how far it has spread. Treatments may include:

• Surgery to remove part of a lobe of a lung, a lobe of a lung, or an entire lung
• Surgery to help relieve symptoms such as airway blockages or fluid buildup
• Radiation therapy
• Chemotherapy
• Targeted therapy
• Drugs that target tumor blood vessel growth (angiogenesis)
• Drugs that target EGFR (epidermal growth factor receptor) – tyrosine kinase inhibitor drug therapies such as gefitinib and erlotinib
• Drugs that target the protein made by an altered ALK gene, such as crizotinib

People who become resistant to available treatments and/or have inoperable lung cancer may want to consider enrollment in clinical trials of new treatments. There are promising areas of research that may offer them additional options. For more on this see Clinicaltrials.gov.