Non Small Cell Lung Cancer

Non Small Cell Lung Cancer

Also called: NSCLC, Non Small Cell Lung Carcinoma

Reviewed By:
Martin E. Liebling, M.D., FACP


Lung cancer is the leading cause of cancer deaths in the United States and the world. There are two main types of lung cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). Most forms of lung cancer are NSCLC.

Lung cancer is the abnormal growth of malignant cells in the tissues of the lungs or airways. NSCLC itself can be divided into subtypes, based on the kind of cells affected. The most common type of non-small cell lung cancer is adenocarcinoma. Other subtypes include squamous cell carcinoma and large-cell carcinoma.

Smoking tobacco is by far the largest risk factor for all types of lung cancer. About 87 percent of lung cancers are due to tobacco products, either through direct smoking or passive exposure to smoking, according to the American Cancer Society.

If caught early, surgery is often recommended to remove the malignant tumor. If the surgery is not successful, or the cancer has spread, radiation therapy may be recommended as a primary treatment. Chemotherapy also may be used as adjuvant therapy to surgery or to treat inoperable disease.

Lung cancers of all types often are not found until the cancer has advanced. The symptoms of lung cancer may not appear until the cancer has metastasized (spread) to other parts of the body. Common symptoms of lung cancer include persistent cough, breathing problems, blood in sputum, recurring respiratory infections, weight loss and fatigue.

Diagnosing NSCLC involves physical examination, blood tests, imaging tools (e.g., ultrasound, MRI, CAT scan), endoscopy and biopsy. Certain types of CAT scans offer some ability to screen for lung cancer, but studies on their effectiveness are still ongoing. The value of cancer screening may not be known for a number of years.

Whether to screen for lung cancer remains a decision to be made between the patient and the physician. The best method to prevent lung cancer of all types is by refraining from or quitting smoking.

About non small cell lung cancer (NSCLC)

Lung cancer is often thought of as a single disease, but it is commonly divided into two main types: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC is by far the most common form, accounting for about 87 percent of lung cancer cases. NSCLC is generally less aggressive than SCLC. SCLC may initially respond more rapidly and dramatically to treatment, but stage for stage, the survival rates are poorer than NSCLC.

Lung cancer is the abnormal growth of malignant cells in the tissues of the lungs or airways. Cancer cells develop because of damage to DNA, the genetic blueprint present in every cell. The body usually can repair damage to DNA. In cancer cells, however, the DNA is not repaired and the abnormal cells reproduce quickly and often live longer than normal cells.

The lungs are sponge-like, cone-shaped organs located in the chest cavity. The left lung has three lobes and the right has two lobes. The lungs are part of the respiratory system and are responsible for the healthy exchange of oxygen and carbon dioxide necessary for the functioning of the body’s cells. A system of small (bronchioles) and larger tubes (bronchi) carry air to and from the lungs for processing in air sacs called alveoli. The oxygen is carried through the bloodstream and made available to the cells in the body. The bloodstream also picks up the carbon dioxide from the cells, a metabolic waste product that is sent to the lungs to exhale.

NSCLC can begin in different regions of the lung. The most common type usually begins in the bronchi, which is the reason it is often called bronchogenic cancer. Although NSCLC is more likely than SCLC to be found early, it still can metastasize (spread) quickly. It can spread through the lymphatic system and bloodstream and by direct invasion of all surrounding structures.

The American Cancer Society (ACS) estimates there will be more than 213,000 new cases of lung cancer in 2007, of which 87 percent will be NSCLC. Lung cancer is the leading cause of cancer deaths with an estimated 161,000 in 2007. The one-year survival rate for both types of lung cancer has increased since the 1970s to approximately 40 percent. However, only about 16 percent of individuals diagnosed with lung cancer live for five years or more after initial diagnosis. Prognosis depends on:

  • Stage of the cancer
  • Type of cancer cell
  • Presence of symptoms
  • Patient’s overall health

Before the 20th century, when cigarettes were not mass produced or readily available, lung cancer in general was rarely seen. As cigarettes became widely available, cases of lung cancer rose dramatically. Today, smoking is responsible for about 87 percent of lung cancer cases, according to the ACS. The connection between cigarettes and lung cancer is overwhelming. Wherever smoking is on the increase in the world, there is a corresponding rise in lung cancer cases.

Lung cancer primarily occurs in older people, with 75 percent of the cases diagnosed in people over age 65. Other risk factors for lung cancer include exposure to radon gas, asbestos and other environmental agents. Despite the high mortality associated with lung cancer, the ACS estimates there are currently 330,000 long-term survivors in the United States. 

Types and differences of NSCLC

Non-small cell lung cancer (NSCLC) accounts for about 87 percent of lung cancers, and small cell lung cancer (SCLC) accounts for the rest. These two varieties are based on how the cells look under a microscope. Types of NSCLC include:

  • Adenocarcinoma. Cancer cells in the mucus-producing glandular cells of the lungs in the bronchi and bronchioles. This is the most common type of lung cancer, accounting for about 40 percent of all lung cancers. This cancer rarely shows symptoms in the early stages and therefore may have metastasized by the time of diagnosis.  It is more likely than the other kinds of NSCLC to begin in the peripheral cells of the lungs and to spread outside of the lungs.

  • Bronchioalveolar carcinoma. This subtype of adenocarcinoma often has spread within the lung before it is discovered.

  • Squamous (epidermoid) cell carcinoma. Cancer of the cells lining the bronchi or airways in the central part of the lungs. These cells are thin and flat and look like fish scales. They can be found in sputum, which assists in early detection. This type is more often cured through early detection and surgical removal than the other types. This form of lung cancer is most common in men. It is the slowest growing of the three non-small cell types. Twenty-five to 30 percent of lung cancers are this type.

  • Large cell carcinoma. Cancer cells originating in the peripheral parts or edges of the lungs. These cells are large, grow and spread aggressively to distant organs. This type is more likely to metastasize to the brain. It accounts for 10 to 15 percent of lung cancers.

  • Adenosquamous carcinoma. A mix of adenocarcinoma and squamous cell carcinoma.

All of these types of NSCLC have a strong association with smoking.

The chart below indicates at which stage each type of NSCLC is usually diagnosed, according to the Centers for Disease Control and Prevention (CDC):

 Stage IStage IIStage IIIStage IVStaging incomplete
Squamous cell21%4%27%22%26%
Large cell12%3%26%36%23%

This chart reveals that distant metastasis may occur early with adenocarcinoma and large cell cancer. These patients are more likely to have higher stage disease at the time of diagnosis.

Signs and symptoms of NSCLC

Like small cell lung cancer, non-small cell lung cancer (NSCLC) often does not show symptoms until it has spread. Many of the symptoms are the same and include:

  • Persistent cough
  • Coughing up blood (hemoptysis)
  • Wheezing
  • Shortness of breath
  • Persistent hoarseness
  • Pain or difficulty breathing or swallowing
  • Repeated pneumonia (fever and mucus-producing cough) or bronchitis
  • Weight loss
  • Loss of appetite
  • Fatigue
  • Swelling of the face and arms

Some lung cancers produce a hormone-like substance that enters the bloodstream and affects distant tissues and organs (a condition called paraneoplastic syndromes). These lung cancers produce certain symptoms, including:

  • High blood calcium levels (hypercalcemia), which can cause increased thirst, frequent urination, constipation, weakness, lethargy, dizziness, cognitive impairment and even coma.
  • Excess growth of bones (hypertrophic osteoarthropathy) that may be painful, sometimes in the fingertips. This is common and may be the presenting symptom of NSCLC.
  • Production of factors that increase the tendency to form blood clots.
  • Excess breast growth in men (gynecomastia)

Diagnosis methods for NSCLC

Initially, the physician obtains a patient’s medical history, including any tobacco use, smoke exposure and family history of cancer. The physician will conduct a physical examination of the patient’s body for signs of disease. Specific focus is placed on lymph node enlargement, masses on the body and in the abdomen (e.g., enlargement of the liver) and unusual chest and breathing signs. Other tests used in diagnosis of non-small cell lung cancer (NSCLC) may include:

  • Blood and urine tests. These tests are taken to determine chemical or hormonal abnormalities that may suggest cancer.
  • Sputum cytology. A sample of sputum or phlegm is taken and undergoes microscopic examination. This test on occasion has lead to early detection of carcinoma.

Most of the diagnostic imaging tests for NSCLC are the same as those for small cell lung cancer (SCLC). They include CAT scans,    MRI (magnetic resonance imaging), x-rays and others.  Other tests include:

  • Bronchoscopy. A fiber optic flexible tube is placed through the mouth, down the trachea (windpipe) and into the breathing passages where the walls of the bronchi can be visualized. Biopsies of lung tissues can be performed during this procedure.
  • Mediastinoscopy. After the patient undergoes general anesthesia, a lighted instrument is placed through an incision in the neck above the sternum and used to view the inside of the chest cavity. The mediastinum (center of the chest) and nearby lymph nodes are viewed for tumors. A biopsy may also be taken.
  • Anterior mediastinotomy. Similar to mediastinoscopy but it is done through a srugical incision in the chest.
  • Thoracentesis. After the skin is numbed, a needle is inserted between the ribs to remove fluid around the lungs, if present,  to observe for cancer cells.
  • Biopsy. A sample of tissue is removed from the suspicious area and analyzed by microscopic examination by a pathologist. Whenever possible, a biopsy is performed with endoscopic procedures.

Treatment options for NSCLC

Treatment for non-small cell lung cancer (NSCLC) is typically coordinated by a cancer care team. The team may include a medical oncologist, surgeon, radiation oncologist and pulmonologist (physician who specializes in lung diseases). Treatment for NSCLC depends on the type and stage of the cancer, as well as other patient factors such as age and general health.

In the earliest stages, NSCLC is typically treated with surgery. Surgery may remove a portion of the lung (wedge resection), an entire lobe (lobectomy) or the entire lung (pneumonectomy). Lymph nodes also may be removed to determine if the cancer has spread. These surgeries are performed under general anesthesia and usually require one to two weeks’ hospitalization.

Radiation therapy may be used to destroy any remaining cancer cells after surgery or to prevent the recurrence of the disease. For patients who are unable to tolerate surgery, radiation may be the primary treatment. Most lung cancer is treated with external beam radiation, which is provided from a machine outside the body.

Chemotherapy may be used in addition to surgery and radiation therapy to prevent a return of cancer cells. Chemotherapy recently has been shown to improve the results if combined with surgery in early stage disease. Chemotherapy may be used to help prevent the recurrence of lung cancer as well.

Other possible treatments of confined and accessible tumors include:

  • Laser therapy. Laser beams (narrow stream of intense light) are used to kill cancer cells.
  • Cryosurgery. A treatment that freezes and destroys cancer tissue.
  • Photodynamic therapy. A cancer treatment that uses drugs that activate when exposed to light, at which point the cells die.

Investigative efforts to improve results include:

  • Chemoprevention. The use of drugs, vitamins and other substances to reduce the risk of developing or recurring cancer.
  • Clinical trials. A physician may recommend participation in a clinical trial that will test new experimental treatments. Patients in all stages of lung cancer can seek to participate in such trials because of the limitations of standard treatments. Clinical trials are conducted for all stages of lung cancer. Experimental therapies may include biological therapy, gene therapy and angiogenesis inhibitors, as well as chemotherapy.
  • Comfort care. All patients have the right to receive treatment for their symptoms, including pain, whether or not they are receiving specific therapy for the cancer. 

Ongoing research for NSCLC

There are numerous agencies, organizations and medical facilities conducting research in the area of lung cancer. The basic areas of focus include:

  • Prevention. Research is focusing on ways to help people quit smoking with a variety of methods, such as nicotine replacement products and medications. Other programs have focused on educating young people on the dangers of smoking to prevent them from starting the habit. Other studies are examining the role of diet, vitamins and supplements in cancer prevention.
  • Earlier diagnosis. Researchers continue to study various diagnostic methods for earlier detection of lung cancer. A large clinical trial called the National Lung Screening Trial (NLST) is studying whether spiral CT scanning of people at high risk will be superior to current imaging techniques. Scientists are also studying methods to detect cancer through sputum and DNA changes in cells.
  • Chemotherapy. Research is focusing on the development of new chemotherapy drugs and drug combinations that can be effective with less toxic side effects. Studies are also being conducted to evaluate effective pairing of chemotherapy drugs with surgery and radiation therapy.
  • Genetics. Scientiests have continued to focus on DNA and their changes that result in cancerous cells. With gene therapy, they hope to develop ways to alter lung cancer by changing DNA or to use DNA to repair gene mutations. Researchers are also studying chromosome abnormalities and their association with cancer risk in families.
  • Antiangiogenesis drugs. Researchers hope to develop certain drugs that may be useful in stopping lung cancer growth by preventing new blood vessels from forming. Blood vessels are necessary to nourish cancer cells, a process known as angiogenesis. Without the nourishment, the cancer would not be able to grow. Antiangiogenesis drugs may be successful in stopping this nourishment process. Researchers are also examining other targeted therapies that may help prevent the growth and spread of cancer cells.
  • Vaccines. Researchers are working to develop vaccines to help the body’s immune system fight cancer. One successful NSCLC vaccine has been deeveloped using patients’ own tumor cells. Some lung cancer vaccines are currently being tested in some clinical trials.

In August 2005, The National Cancer Institute (NCI) announced a new initiative to aggressively fight lung cancer. Using an integrated approach, its mission is to eliminate suffering and death due to lung cancer by 2015. The new plan will focus on three critical areas:

  • Reducing the risk factors for lung cancer by achieving better tobacco control
  • Earlier detection and treatment of lung cancer and pre-cancer
  • Targeting advanced therapies with ongoing research

As part of the plan, an Image Response Assessment Team (IRAT) will be established. The IRAT will focus on the analysis of lung cancer tumor markers and their contribution to lung cancer treatment. Researchers also intend to use advanced imaging strategies to understand lung cancer development and the response to various treatments.

Staging for NSCLC

Non-small cell lung cancer (NSCLC) is staged by tumor size, level of spread to the lymph nodes and spread to other organs:

  • Stage 0. Cancer is located in the air passages only. No lung tissue is affected. Cancer treated at this stage can often be cured.

  • Stage I. Cancer is in the lung tissue only. Lymph nodes are not affected.

  • Stage II. Cancer is located in the lung and nearby lymph nodes and the chest wall.

  • Stage IIIA. Cancer is located in the lung and distant lymph nodes.

  • Stage IIIB. Cancer is located in the lung and spread locally to the heart, blood vessels, trachea and esophagus within the chest wall.

  • Stage IV. Cancer may be located in both lungs and has spread to distant organs such as the liver, brain or bones.

  • Recurrent. Cancer that recurs after treatment and may return to the lung or other parts of the body.

Stages 0 through IIIA are potentially resectable, meaning they can be surgically removed. Stages IIIB and IV are generally treated with chemotherapy and/or radiation therapy and other treatments. Radiation and/or chemotherapy may be combined with surgery to either reduce the size of a tumor and to improve surgical results.

The five-year survival rate for non-small cell lung cancer is as follows:

Stage5-Year Survival Rate
I47 percent
II26 percent
III8 percent
IV2 percent
All stages
15 percent

Questions for your doctor about NSCLC

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about non-small cell lung cancer (NSCLC):

  1. What is the difference between NSCLC and small cell lung cancer?
  2. What tests will be used to diagnose NSCLC?
  3. How will my biopsy be conducted?
  4. When and from whom will I receive the biopsy results?
  5. What type of NSCLC do I have?
  6. What is the stage of my cancer?
  7. What is the prognosis based on my cancer type and stage?
  8. Am I a candidate for surgery? If so, what will be removed?
  9. What can I expect in terms of recovery?
  10. How successful is surgery in curing my type of cancer?
  11. Will I need other treatments in addition to surgery?
  12. What are the risks with these treatments?
  13. How will I be monitored after treatment?
  14. What are the signs that my cancer has spread?
  15. What are the chances my cancer will return?
  16. Am I at greater risk for other cancers?
  17. Are there any clinical trials appropriate for me?
  18. Can you recommend a lung cancer support group?
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