Lung Cancer

Smoking is the biggest risk factor for lung cancer.

• Lung cancer is a group of diseases characterized by abnormal growths (cancers) that started in the lungs.
• People should seek medical care if they have blood in their sputum when coughing, are experiencing unexplained weight loss, or have sudden shortness of breath.
• Treatment options depend on the type of lung cancer present and the stage of the tumor.

Lung cancer comprises a group of different types of tumors. Lung cancers usually are divided into two main groups that account for about 95% of all cases.

• The division into groups is based on the type of cells that make up the cancer.
• The two main types of lung cancer are characterized by the cell size and cell type of the tumor when viewed under the microscope. They are called small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). NSCLC includes several subtypes of tumors.
• SCLCs are less common, but they grow more quickly and are more likely to metastasize than NSCLCs. Often, SCLCs have already spread to other parts of the body when the cancer is diagnosed.
• About 5% of lung cancers are of rare cell types, including carcinoid tumor, lymphoma, and others.

The main specific types of primary lung cancers are as follows:

• Adenocarcinoma (an NSCLC) is the most common type of lung cancer, making up 30%-40% of all cases.
• Squamous cell carcinoma (an NSCLC) is the second most common type of lung cancer, making up about 30% of all cases.
• Large cell cancer (another NSCLC) makes up 10% of all cases.
• SCLC makes up 20% of all cases.
• Carcinoid tumors account for 1% of all cases.

Risk factors for lung cancer include smoking, exposure to air pollution, and genetics.

Cigarette smoking is the most important cause of lung cancer. Research as far back as the 1950s clearly established this relationship.

• Cigarette smoke contains more than 4,000 chemicals, many of which have been identified as causing cancer.
• A person who smokes more than one pack of cigarettes per day has a 20-25 times greater risk of developing lung cancer than someone who has never smoked.
• Once a person quits smoking, his or her risk for lung cancer gradually decreases. About 15 years after quitting, the risk for lung cancer decreases to the level of someone who never smoked.
• Cigar and pipe smoking increases the risk of lung cancer but not as much as smoking cigarettes.

About 90% of lung cancers arise due to tobacco use. The risk of developing lung cancer is related to the following factors:

• The number of cigarettes smoked
• The age at which a person started smoking
• How long a person has smoked (or had smoked before quitting)

Other causes of lung cancer, including causes of lung cancer in nonsmokers, include the following:

• Passive smoking, or secondhand smoke, presents another risk for lung cancer. An estimated 3,000 lung cancer deaths occur each year in the U.S. that are attributable to passive smoking.
• Air pollution from motor vehicles, factories, and other sources probably increase the risk for lung cancer, and many experts believe that prolonged exposure to polluted air containing cancer-causing chemicals is similar to prolonged exposure to passive smoking in terms of risk for developing lung cancer.
• Asbestos exposure increases the risk of lung cancer nine times. A combination of asbestos exposure and cigarette smoking raises the risk to as much as 50 times. Another cancer known as mesothelioma (a type of cancer of the inner lining of the chest cavity and the outer lining of the lung called the pleura, or of the lining of the abdominal cavity called the peritoneum) is also strongly associated with exposure to asbestos.
• Lung diseases, such as tuberculosis (TB) and chronic obstructive pulmonary disease (COPD), also create a risk for lung cancer. A person with COPD has a four to six times greater risk of lung cancer even when the effect of cigarette smoking is excluded.
• Radon exposure poses another risk.
  • Radon is a byproduct of naturally occurring radium, which is a product of uranium.
  • Radon is present in indoor and outdoor air.
  • The risk for lung cancer increases with significant long-term exposure to radon, although no one knows the exact risk. An estimated 12% of lung cancer deaths are attributable to radon gas, or about 21,000 lung cancer-related deaths annually in the U.S. Radon gas is the second leading cause of lung cancer in the United States after cigarette smoking. As with asbestos exposure, smoking greatly increases the risk of lung cancer with radon exposure.
• Certain occupations where exposure to arsenic, chromium, nickel, aromatic hydrocarbons, and ethers occurs may increase the risk of lung cancer.
• A person who has had lung cancer is more likely to develop a second lung cancer than the average person is to develop a first lung cancer.
• There is currently not enough evidence to determine whether vaping, or the use of e-cigs, causes lung cancer. Vaping is known to introduce chemicals into the lung tissue, so there is a possibility that it also increases cancer risk.
• While smoking marijuana has not been linked to lung cancer, smoke from marijuana is known to contain levels of tar and certain chemicals that are similar to tobacco smoke. Therefore, it is unclear whether marijuana could be related to lung cancer.
   

Lung cancer is the leading cause of cancer deaths in women and men both in the United States and throughout the world. Lung cancer has surpassed breast cancer as the leading cause of cancer deaths in women for the past 25 years. In the United States, there are more deaths due to lung cancer than the number of deaths from colon and rectal, breast, and prostate cancer combined.

Most lung tumors are malignant. This means that they invade and destroy the healthy tissues around them and can spread throughout the body. The lung is a bad place for a cancer to arise because it contains a very rich network of both blood vessels and lymphatic channels through which cancer cells can spread.

• The tumors can spread to nearby lymph nodes or through the bloodstream to other organs. This process of spread is called metastasis.
• When lung cancer metastasizes, the tumor in the lung is called the primary tumor, and the tumors in other parts of the body are called secondary or metastatic tumors.

Some tumors in the lung are metastatic from cancers elsewhere in the body. The lungs are a common site for metastasis. If this is the case, the cancer is not considered to be lung cancer. For example, if prostate cancer spreads via the bloodstream to the lungs, it is metastatic prostate cancer (a secondary cancer) in the lung and is not called lung cancer.

Lung cancer symptoms include cough (chronic, recurrent), fatigue, weight loss, shortness of breath or wheezing, coughing up phlegm that contains blood, and chest pain.

Up to one-fourth of all people with lung cancer may have no symptoms when the cancer is diagnosed. These cancers usually are identified incidentally when a chest X-ray is performed for another reason. The majority of people, however, develop symptoms. The symptoms are due to direct effects of the primary tumor, to effects of metastatic tumors in other parts of the body, or to disturbances of hormones, blood, or other systems caused by the cancer.

Symptoms of primary lung cancers include cough, coughing up blood, chest pain, and shortness of breath.

• A new cough in a smoker or a former smoker should raise concern for lung cancer.
• A cough that does not go away or gets worse over time should be evaluated by a health care professional.
• Coughing up blood (hemoptysis) occurs in a significant number of people who have lung cancer. Any amount of coughed-up blood is cause for concern.
• Chest pain is a symptom in about one-fourth of people with lung cancer. The pain is dull, aching, and persistent.
• Shortness of breath usually results from a blockage to the flow of air in part of the lung, collection of fluid around the lung (pleural effusion), or the spread of tumor throughout the lungs.
• Wheezing or hoarseness may signal blockage or inflammation in the lungs that may go along with cancer.
• Repeated respiratory infections, such as bronchitis or pneumonia, can be a sign of lung cancer.

Symptoms of metastatic lung tumors depend on the location and size. About 30% to 40% of people with lung cancer have some symptoms or signs of metastatic disease.

• Lung cancer most often spreads to the liver, the adrenal glands, the bones, and the brain.
• Metastatic lung cancer in the liver may cause a loss of appetite, feeling full early on while eating, and otherwise unexplained weight loss.
• Metastatic lung cancer in the adrenal glands also typically causes no symptoms.
• Metastasis to the bones is most common with small cell cancers but also occurs with other lung cancer types. Lung cancer that has metastasized to the bone causes bone pain, usually in the backbone (vertebrae), the large bones of the thigh (the femurs), the pelvic bones, and the ribs.
• Lung cancer that spreads to the brain can cause difficulties with vision, weakness on one side of the body, and/or seizures.

Paraneoplastic syndromes are the remote, indirect effects of cancer not related to direct invasion of an organ by tumor cells. Often they are caused by chemicals released from the cancers. Symptoms include the following:

• Clubbing of fingers -- the depositing of extra tissue under the fingernails
• New bone formation -- along the lower legs or arms
• Increased risk of blood clots in the arms, legs, or lungs
• Low sodium levels
• High calcium levels
• Low potassium levels
• Degenerative conditions of the nervous system otherwise unexplained.

See a health care provider as soon as possible if any of the following develop:

• Any symptom of lung cancer
• New cough or change in an existing cough
• Hemoptysis (flecks of blood in the sputum when coughing)
• Unexplained weight loss
• Unexplained persistent fatigue
• Unexplained deep aches or pains

Go immediately to the nearest hospital emergency department if any of the following occur:

• Coughing up a large amount of blood
• Sudden shortness of breath
• Sudden weakness
• Sudden vision problems
• Persistent chest pain

Upon hearing about the symptoms, a health care provider will formulate a list of possible diagnoses. The doctor will ask questions about the symptoms, medical and surgical history, smoking and work history, and other questions about lifestyle, overall health, and medications.

Unless severe hemoptysis is occurring, a chest X-ray will most likely be performed first to look for a cause of the respiratory symptoms.

• The X-ray may or may not show an abnormality.
• Types of abnormalities seen in lung cancer include a small nodule or nodules or a large mass.
• Not all abnormalities observed on a chest X-ray are cancers. For example, some people develop scarring and calcium deposits in their lungs that may look like tumors on a chest X-ray.

In most cases, a CT scan or MRI of the chest will further define the problem.

• If symptoms are severe, a medical professional may perform a CT scan or MRI right away instead of a chest X-ray.
• The advantages of CT scan and MRI are that they show much greater detail than X-rays and are able to show the lungs in three dimensions.
• These tests help determine the stage of the cancer by showing the size of the tumor or tumors.
• They can also help identify spread of the cancer into nearby lymph nodes or certain other organs.

If a person's chest X-ray or scan suggests that a tumor is present, he or she will undergo a procedure for diagnosis. Diagnosis requires analysis of cells or tissue sufficient to make the cancer diagnosis with certainty.

• This procedure involves collection of sputum, removal of a small piece of the tumor tissue (biopsy) or a small volume of fluid from the sac around the lung.
• The retrieved cells are reviewed under a microscope by a doctor who specializes in diagnosing diseases by looking at cell and tissue types (a pathologist).
• Several different ways exist to obtain these cells.

Sputum testing: This is a simple test that is sometimes performed to detect cancer in the lungs.

• Sputum is thick mucus that may be produced during a cough.
• Cells in the sputum can be examined to see if they are cancerous. This is called cytology testing.
• This is not a completely reliable test. If negative, the findings usually need to be confirmed by further testing.

Bronchoscopy: This is an endoscopic test, meaning that a thin, flexible, lighted tube with a tiny camera on the end is used to view organs inside the body.

• Bronchoscopy is endoscopy of the lungs. The bronchoscope is inserted through the mouth or nose and down the windpipe. From there, the tube can be inserted into the airways (bronchi) of the lungs.
• A tiny camera transmits images back to a video monitor.
• The physician operating the bronchoscope can look for tumors and collect samples of any suspected tumors.
• Bronchoscopy can usually be used to determine the extent of the tumor.
• The procedure is uncomfortable. A local anesthetic is administered to the mouth and throat as well as sedation to make bronchoscopy tolerable.
• Bronchoscopy has some risks and requires a specialist proficient in performing the procedure.

Needle biopsy: If a tumor is on the periphery of the lung, it usually cannot be seen with bronchoscopy. Instead, a biopsy is taken through a needle inserted through the chest wall and into the tumor.

• Typically, a medical professional uses a chest X-ray or CT scan to guide the needle.
• This procedure is safe and effective in obtaining sufficient tissue for diagnosis. After the chest surface is cleaned and prepared, the skin and the chest wall are numbed.
• The most serious risk with this procedure is that the needle puncture may cause an air leak from the lung (pneumothorax). This air leak occurs in as many as 3%-5% of cases. Although this condition can be dangerous, it is almost always recognized quickly and treated without serious consequences.
• Endoscopic ultrasound with fine-needle aspiration of an abnormal mass or lymph node may also be performed at the time of bronchoscopy.

Thoracentesis: This a procedure that removes a sample of fluid from the pleural cavity surrounding the lungs. Lung cancers, both primary and metastatic, can cause fluid to collect in the sac surrounding the lung. This fluid is called a pleural effusion.

• The fluid usually contains cells from the cancer.
• Sampling this fluid can confirm the presence of cancer in the lungs.
• The fluid sample is removed by a needle in a procedure similar to needle biopsy.
• Thoracentesis can be important for both staging and diagnosis of the condition.

Thoracotomy: Sometimes a lung cancer tumor cannot be reached by bronchoscopy or needle procedures.

• In these cases, the only way to obtain a biopsy is by performing an operation.
• The chest is opened (thoracotomy), and as much of the tumor as possible is removed surgically. The removed tumor is then examined microscopically.
• Unfortunately, this operation may not be successful in removing all tumor cells if the tumor is large or has spread to the lymph nodes outside of the lungs.
• Thoracotomy is a major operation that is performed in a hospital.

Mediastinoscopy: This is another endoscopic procedure. It is performed to determine the extent that the cancer has spread into the area of the chest between the lungs (the mediastinum).

• A small incision is made into the lower part of the neck above the breastbone (sternum). A variation is to make the incision in the chest.
• A mediastinoscope that is similar to a bronchoscope is inserted behind the breastbone.
• Samples of the lymph nodes are taken to evaluate for cancer cells.
• Mediastinoscopy is a very important step to determine whether the tumor can be surgically removed or not.

Staging is the process of establishing the extent of the cancer once the diagnosis is made, so that an appropriate course of treatment can be planned.

The results of all of the diagnostic testing and procedures are reviewed to determine what information might be needed to accurately stage the patient.

A PET scan assesses the presence or absence of distant metastases very well. If there are any questions about the patient's neurologic status, an MRI of the brain may be needed. CT scans of the chest abdomen and pelvis with contrast will likely be done to correlate with the PET scan imaging. Other tests may include the following:

• Pulmonary function tests to assess breathing capacity
• Blood tests to identify any chemical imbalances, blood disorders, or other problems that might complicate treatment
• A bone scan can determine whether the cancer has spread to the bones.
• A bone scan and bone X-rays, particularly in the absence of PET scan availability, can determine whether the cancer has spread to the bones.
• Molecular testing on the cancerous tissue may help to determine eligibility for specific options for treatment.

Staging systems classify the patient's disease based upon the results of the evaluation completed.

Staging: Staging is a method of classifying the tumor for purposes of treatment planning.

• Staging is based on size of the tumor, location of the tumor, and degree of metastasis of the tumor (if any).
• The treatment will be individually tailored to the tumor stage.
• Tumor stage is related to the outlook for cure and survival (prognosis). The higher the tumor stage, the less likely the disease will be cured.
• In contrast to staging, "grading" of lung cancer involves classification of the tumor cells under a microscope. The grade of a cancer is a measure of the abnormality of the cancer cells when compared to normal cells. High-grade tumors have a very abnormal appearance and tend to grow rapidly.

• Treatment decisions in lung cancer depend first on whether SCLC or non-small cell lung cancer is present.
• Treatment also depends on tumor stage. In NSCLC, the performance status of the patient is a key determinant of the likelihood of benefit from treatment. Performance status compares the patient's functional status -- how well they are doing as compared to their pre-illness levels of day to day activity.
• Risk of side effects and complications increase, and the chance of benefit decreases with declining performance status. In SCLC, a rapid response to treatment occurs often enough to overcome this issue.
• The most commonly used treatments today for lung cancer involve surgery, radiation therapy, chemotherapy, and targeted therapies.

In SCLC (small cell lung cancer), patients with limited disease at presentation (disease confined to one lung and its regional lymph nodes) are distinguished from those with extensive stage disease, which includes all cases not classified as limited. Limited stage disease, treated with radiation and chemotherapy (including prophylactic, or preventative, brain radiation therapy), will frequently have all evidence of disease disappear for a time and are said to enter remission. About 80% will relapse within 2 years, but as many as 10% to 15% may survive 5 or more years.

In extensive stage SCLC, response to chemotherapy and palliative radiation occurs less frequently, and survival beyond 2 years is rare. Median survival is about 13 months.

In NSCLC, non-small cell lung cancer, those patients deemed medically inoperable may be treated with curative intent with radiation therapy with 5-year survival in early stage disease from 10% to 25%.

In advanced inoperable stages of NSCLC, treatment remains non-curative, but palliative radiation therapy and chemotherapy can provide meaningful symptom improvement and prolongation of life as compared to only supportive care.

The use of targeted therapies in NSCLC has been of increasing importance especially in adenocarcinoma of the lung. Agents with lower levels of toxicity and efficacy at least as good as chemotherapy have been identified which can be utilized in lung cancer patients whose cancer cells show mutations or alterations in specific genes. In addition, the use of agents targeted to other features of lung cancer, such as tumor factors to recruit blood vessels to support their growth or factors involved in the immune response, have been developed and have proven advantageous in the palliative treatment of NSCLC.

Side effects of radiation therapy vary with the area being treated, the dose being given, and the type of radiation technique and equipment being used.

Side effects of chemotherapy again vary with the drug being given, the dose being used, and the patient's unique sensitivity to the type of chemotherapy selected. There are a wide variety of both chemotherapies and targeted agents that may be tried in these cases.

Finally, preventive or adjuvant chemotherapy has been utilized in operable stages of NSCLC in an attempt to eradicate microscopic, hidden deposits of lung cancer that may have escaped prior to surgery and remain undetectable for now but will cause relapse later if not killed.

Clinical trials are always in progress to look for new therapies or combinations of therapies for people with all types and stages of lung cancer. Participating in such a study is another treatment option.

Following surgery for operable lung cancer cases, there is an increased risk of developing a second primary lung cancer as well as risk that the original tumor will come back.

• Many lung cancers come back within the first 2 years after treatment.
• Regular testing should be performed so that any recurrence can be identified as early as possible.
• A person who has undergone surgery should receive follow-up care and examinations according to recommendations from the treatment team.

Palliative and Hospice Care

Palliative care refers to a specialty of patient care focused on helping the patient to understand their options for treatment, to be certain that both physical, psychological, social, financial, and other potential stressors and symptoms are being addressed, and that advance directive issues are being addressed. It is not the same as hospice care. It is appropriate during both curative treatment and during times when treatment is not expected to be curative. Palliative care consultation in combination with usual non-curative chemotherapy and radiation for advanced lung cancer has been shown to be associated with a prolonged median survival as compared to chemotherapy and radiation alone.

Hospice care refers to care provided to optimize symptom control when all other treatment options have been unsuccessful or are declined. It focuses on supporting the patient and their family with home visits, equipment, counseling, and medication and coordination of care to maintain what quality of life can be provided at that point in the illness. This may mean, for example, keeping the patient at home rather than readmitting the patient for terminal symptom management, which can be provided at home with specialized support.

• The patient, his or her family, and the doctor will probably recognize when the patient has reached the point that hospice care is necessary.
• Whenever possible, the transition to hospice care should be planned in advance.
• Planning should begin with a three-way conversation between the patient, someone representing the patient (if he or she is too ill to participate), and the health care professional.
• During these meetings, likely outcomes, medical issues, and any fears or uncertainties can be discussed.

Hospice care may be given at home, in a hospital if home care is not possible, or in a hospice facility.

• Breathlessness will be treated with oxygen and medications such as opioids, which are narcotic drugs such as fentanyl, morphine, codeine, methadone, oxycodone, and dilaudid.
• Pain management includes anti-inflammatory medications and opioids. The patient is encouraged to participate in determining doses of the pain medication, because the amount needed to block pain will vary from day to day.
• Other symptoms, such as anxiety, lack of sleep, and depression, are treated with appropriate medications and, in some cases, complementary therapies.

Prevention primarily focuses on minimizing risk factors, primarily smoking cessation.

Smokers who wish to quit obtain benefit from many different strategies, including nicotine replacement therapy with patch or gum, varenicline (Chantix), counseling, and support groups. Smokers who do not wish to quit, but are told that they must, often will relapse if they can ever quit at all.

Passive tobacco smoke exposure as secondhand smoke can also cause lung cancer and should be avoided.

Radon detection kits for testing the home and workplace can be recommended. Radon exposure is a cause of more than 10,000 lung cancer deaths per year worldwide and is a leading cause of lung cancer in nonsmokers.

Screening recommendations have undergone some recent changes as regards this significant health problem. The U.S. Preventive Services Task Force (USPSTF) has recommended and the Centers for Medicare and Medicaid Services (CMS) has further agreed with the following recommendation:

• Adults between 55 and 77 years of age with a history of at least 30 pack years of cigarette smoking, either currently smoking, or who have quit in the past 15 years, and who have discussed the risks and benefits of CT screening with the ordering physician and have undergone documented smoking cessation counseling should undergo annual low-dose CT scan screening.

Such testing has been demonstrated to reduce the risk of dying from lung cancer by 15% to 20% as compared to those receiving only an annual chest X-ray.

Overall (considering all types and stages of lung cancer), 19% of people with lung cancer survive for at least 5 years. Survival rates tend to be low when compared to the 65% 5-year survival rate for colon cancer, 91% for breast cancer, and over 99% for prostate cancer.

• People who have early stage (stage I) NSCLC and undergo lung surgery have a 60%-70% chance of surviving 5 years.
• People with extensive nonoperable lung cancer have an average survival duration of 9 months or less.
• Those with limited SCLC who receive chemotherapy have a 2-year survival rate of 20% to 30% and a 5-year survival rate of 10%-15%.
• Less than 5% of people with extensive-stage SCLC (small cell cancers) are alive after 2 years, with a median survival range of 8-13 months.

Is There a Cure for Lung Cancer?

If lung cancer is found at an early stage, at least half of those affected patients will be alive and free of recurrent cancer 5 years later. Once lung cancer has metastasized, that is, spread to other distant organs, the five-year overall survival is around 6%.

Cancer occurs when normal cells undergo a transformation that causes them to grow abnormally and multiply without control and potentially spread to other parts of the body. The cells form a mass or tumor that differs from the surrounding tissues from which it arises. Cancers are also called malignant tumors. Such tumors are dangerous because they take oxygen, nutrients, and space from healthy cells and because they invade and destroy or reduce the ability of normal tissues to function.

Living with cancer presents many new challenges for people with cancer and for their family and friends.

• People with cancer will probably have many worries about how the cancer will affect them and their ability to live a normal life, that is, to care for their family and home, to hold a job, and to continue the friendships and activities they enjoy.
• Many people feel anxious and depressed. Some people feel angry and resentful; others feel helpless and defeated.

For most people with cancer, talking about their feelings and concerns helps.

• Friends and family members can be very supportive. They may be hesitant to offer support until they see how the person with cancer is coping. People with cancer should not wait for friends or family to bring it up; if they want to talk about their concerns, they should let friends and family know.
• Some people do not want to burden their loved ones or just prefer talking about their concerns with a more neutral professional. Discussing feelings and concerns about having cancer with a social worker, counselor, or member of the clergy can be helpful. A surgeon or oncologist should be able to recommend someone.
• Many people with cancer are profoundly helped by talking to other people who have cancer. Sharing concerns with others who have been through the same thing can be remarkably reassuring. Support groups of people with cancer may be available through the medical center where treatment is being received. The American Cancer Society also has information about support groups all over the United States.