Lung Cancer: The Basics

Christopher Dolinsky, MD and Christine Hill-Kayser, MD
Affiliation: The University of Pennsylvania Medical School
Last Modified: February 27, 2008

What are the lungs?

The lungs are two spongy organs found in the chest. They are responsible for delivering oxygen to the bloodstream. When you take a breath in, air moves into the lungs causing them to expand. The air can then come very close to blood that is traveling in small vessels called capillaries. When you breathe out, you exhale substances that you don't need like carbon dioxide. The lungs are specially designed to place blood in close contact with as much air as possible, so their tissues are very delicate. The right lung has three sections called lobes. The left lung has only two lobes. Air comes in through your mouth and nose and then travels down a tube to the lungs called the trachea. The trachea divides into smaller branches called bronchi, and the bronchi keep dividing and dividing like branches on a tree. As the branches get smaller, they are called bronchioles. At the end of the branches, there are little sacs of air called alveoli. The air comes into contact with blood in the alveoli. The lungs are exposed to whatever you breathe in, so any toxic chemicals or pollutants in the air you breathe can get into your body through your lungs.

What is lung cancer?

Lung cancer happens when cells in the lung begin to grow out of control and can then invade nearby tissues or spread throughout the body. Large collections of cancer cells are called tumors. Cells in any of the tissues in the lung can develop cancer; but most commonly, lung cancer comes from the lining of the bronchi. Lung cancer is not really thought of as a single disease, but rather a collection of several diseases that are characterized by the cell type that makes them up, how they behave, and how they are treated. Lung cancer is divided into two main categories:

• Small cell lung cancer (SCLC) - the rarer of the two types (about 20% of all lung cancers), small cell lung cancer is more aggressive than non small cell lung cancer because is grows more quickly and is more likely to spread to other organs
• Non small cell lung cancer (NSCLC) - the more common of the two types (80% of all lung cancers), non small cell lung cancer is generally slower growing than small cell lung cancer and is divided into three different types based on how the cells look that make it up - adenocarcinoma, large cell carcinoma, and squamous cell carcinoma

Am I at risk for lung cancer?

Lung cancer is the most common cause of cancer death in the world for both men and women. In the United States alone, it is estimated that 163,510 people will die from lung cancer in 2005. In comparison, 127,500 people are expected to die from colon, breast and prostate cancer combined in 2005 (the 2nd, 3rd, and 4th most common cancers in the U.S.). In the U.S., there has been a striking increase in the number of women getting lung cancer; in the 1990s, lung cancer overtook breast cancer as the most common cause of cancer death amongst women. This probably reflects increase incidence of smoking among women.

Every smoker is at risk for lung cancer. It is estimated that 87% of all cases of lung cancer are caused by cigarette smoking. The major risk factor for lung cancer is cigarette smoking. Your risk of getting lung cancer from cigarette smoking increases the longer you smoke, the more you smoke, and the deeper you inhale. Smoking low tar cigarettes does not prevent you from getting lung cancer. Importantly, if you quit smoking, your risk of getting lung cancer declines. The longer you go without smoking, the greater your risk declines. It is never too late to quit because your risk declines somewhat no matter how long you have been smoking. Even patients who have been diagnosed with lung cancer have been demonstrated to respond to treatment better and live longer if they quit smoking at the time of their diagnosis.

Smoking also has an affect on people around you. Second-hand smoke, or smoke inhaled when you are near someone smoking, is another risk factor for lung cancer. It is estimated that 17% of cases of lung cancer in non-smokers are caused by second-hand smoke exposure in childhood and adolescence. Non-smoking spouses of smokers are 30% more likely than spouses of non-smokers to get lung cancer. Even though many people don't inhale them, smoking pipes and cigars is a risk factor for lung cancer as well. The more pipes or cigars you smoke, the more likely you are to get lung cancer. Although it is not as well established as cigarette smoking, smoking marijuana is also a risk factor for getting lung cancer. Both the magnitude and duration of marijuana use seems to be related to your overall risk.

Although smoking cigarettes is by far the most common and important risk factor for getting lung cancer, there are some environmental exposures that increase your risk for lung cancer as well. People who work with asbestos are more likely to get lung cancer; and if they smoke cigarettes too, their risk rises even higher. Asbestos is found in industries like shipbuilding, brake manufacture, insulation/fireproofing, and asbestos mining and production. Other workers who may have a higher risk of lung cancer are those exposed to arsenic, chromium, nickel, vinyl chloride, hard metal dusts, talc, uranium, and gasoline and diesel exhaust fumes.

Radon is an invisible, odorless gas that exists naturally in areas where there is a lot of uranium in the ground. Radon can collect in both uranium mines and peoples' houses. Exposure to radon has been associated with a slightly increased risk of lung cancer. You can check for radon with detectors available at a hardware store, and getting rid of it is usually as easy as opening a basement window.

People who have already had lung cancer are at risk for getting it again. A history of interstitial lung disease or tuberculosis (TB) also increases your risk of getting lung cancer. However, it should be stressed that cigarette smoking is far and away the most important and dangerous risk factor for developing lung cancer.

How can I prevent lung cancer?

The best way to prevent lung cancer is to quit smoking, or to never start in the first place. You should try and avoid being around people who are smoking; and also avoid pipes, cigars, and marijuana. If you live in an area with radon, you should make sure there is adequate ventilation in your basement to get rid of it. Use a detector to make sure the radon levels are low. If you work in an industry where you are exposed to substances known to cause lung cancer, make sure to use all the proper protective equipment and attire made available by your employer.

There has been some suggestion that a diet high in fruits and vegetables may decrease your risk of lung cancer. This has yet to be definitively proven. Many substances, including antioxidants like vitamin A, vitamin E, and beta-carotene, have been suggested to decrease your risk of lung cancer. None of these has been shown to be beneficial in randomized controlled trials and cannot be recommended for this purpose. In fact, large clinical trials have shown and increased risk of lung cancer in patients that take increased quantities of vitamin E, vitamin A, and beta-carotene.

The future of lung cancer prevention will rely on sophisticated analysis of patients' genes and molecular markers for lung cancer risk; this coupled with "smart drug" design and novel imaging techniques may one day help decrease the risk of developing lung cancer.

What screening tests are available?

It is generally held that there are no good screening tests available for lung cancer. In all of the studies conducted to date, comparing people who are screened with chest x- rays and/or sputum samples, there has never been a documented decrease in deaths from lung cancer due to screening. However, this is an issue that is hotly debated because some studies have shown that cancers can be picked up in earlier stages if patients are screened with chest x-rays. The problem is that picking up the cancers earlier hasn't translated to a decrease in deaths because of the screening. Some doctors may choose to screen high risk patients (usually those patients over 50 years old with a significant smoking history) with annual chest x-rays in an effort to find cancers earlier, however, no professional society has endorsed this practice. Currently, there is debate about the utility of screening people with CT scans (3-D x-rays that are more sensitive than standard chest x-rays). The debate is the same as with chest x-rays; no one has demonstrated a decreased mortality in patients screened with CT scans thus far. As more data is collected and more sophisticated imaging techniques are developed, perhaps one day there will be a good screening test for lung cancer. In the absence of a good screening tool, the best way we can decrease the number of lung cancer deaths is to help people to quit smoking.

What are the signs of lung cancer?

Unfortunately, the early stages of lung cancer may not have any symptoms. As the tumor grows in size, it can produce a variety of symptoms including:

• cough (especially one that doesn't go away or gets worse in character)
• chest pain
• shortness of breath
• coughing up blood or bloody phlegm
• new onset hoarseness or wheezing
• recurrent problems with pneumonia or bronchitis
• weight loss
• loss of appetite
• fatigue
• bone pain
• dizziness or double vision
• numbness or tingling in your arms or legs
• turning yellow (jaundice)
• seizures

Many of these symptoms are non-specific, and could represent a variety of different conditions; however, your doctor needs to see you if you have any of these problems. Most patients (85%-90%) who are diagnosed with lung cancer have symptoms that prompt a doctor to order tests to look for a problem. A cough is the most common presenting symptom of lung cancer; however, many long term smokers have a chronic cough, so it is especially important for someone with a chronic cough to see their doctor if their cough changes in character or severity.

How is lung cancer diagnosed and staged?

When a patient at risk for lung cancer has symptoms suggestive of a lung tumor, they will usually first be referred for a chest x-ray. If the chest x-ray looks abnormal, then they will be referred for a CT scan (a 3-D x-ray) to better characterize the lesion. The other thing that your doctor may do is called sputum cytology, which means examining your phlegm for cancer cells.

Depending on the results of the sputum cytology, chest x-rays, and/or CT scans, your doctors may recommend that you have a biopsy. A biopsy is the only way to know for sure if you have cancer, because it allows your doctors to see your cells under a microscope. There are different ways that a biopsy may be done. Your doctors may want to do fiberoptic bronchoscopy, which means putting a thin, lighted tube down your nose or mouth and into your lung to look at the tumor and take samples of it. Another way to get a biopsy sample is to do a needle biopsy, which means placing a needle through the skin into the tumor to get cells. Sometimes, tumors cells can get into the fluid around your lungs, and your doctor may want to drain off some fluid (called a thoracentesis) and examine it under a microscope.

Once the tissue is removed, a doctor known as a pathologist will review the specimen. The pathologist can tell if it is cancer or not; and if it is cancerous, then the pathologist will characterize it by what type of tissue it arose from and what subtype of lung cancer it is, how abnormal it looks (known as the grade), and whether or not it is invading surrounding tissues.

In order to guide treatment and offer some insight into prognosis, lung cancer is staged into different groups. The staging system is different for the two main types of lung cancer: small cell lung cancer (SCLC) and non small cell lung cancer (NSCLC). This staging is done in a limited fashion before surgery taking into account the size of the tumor on CT scan, where it is, and any evidence of spread to other organs that is picked up with imaging modalities; and it is done definitively after a surgical procedure that removes lymph nodes and allows a pathologist to examine them for signs of cancer. Sometimes, surgeons will do procedures just for staging. One such procedure is called a mediastinoscopy. A mediastinoscopy is a procedure in which a surgeon uses a scope to sample the lymph nodes near the trachea (the windpipe) so that the pathologist can examine them for signs of cancer. Often, your doctors will want to know the exact stage of your cancer before treatment is planned, because the stage of the cancer drastically affects how it is treated. The staging system is somewhat complex, but here is a simplified version of it:

Small Cell Lung Cancer - divided into two stages

1. Limited Stage - means the cancer is on only one side of the chest (lung and/or lymph nodes), so it could be reasonably treated with a radiation field
2. Extended Stage - means the cancer is on both sides of the chest (spread to both lungs and/or lymph nodes on both sides of the body) or spread outside of the chest to other areas of the body, so it could not be reasonably treated with a radiation field

Non Small Cell Lung Cancer - divided into four main stages

1. Stage IA- the tumor is less than 3 cm, isn't in a main bronchus, and hasn't spread to any lymph nodes
   Stage IB - the tumor doesn't invade any organs, isn't too close to the trachea if it is in the main bronchus, doesn't cause obstruction of the lung, and hasn't spread to any lymph nodes
2. Stage IIA- the tumor is less than 3 cm, isn't in a main bronchus and has spread to lymph nodes on the same side as the tumor
   Stage IIB - the tumor doesn't invade any organs, isn't too close to the trachea if it is in the main bronchus, doesn't cause obstruction of the entire lung but has spread to hilar lymph nodes on the same side as the tumor.
3. Stage IIIA - the tumor can have spread to different types of lymph nodes than Stage II (called mediastinal or subcarinal), but they are still on the same side as the tumor and it hasn't invaded any vital organs
   Stage IIIB - the tumor has either invaded vital adjacent organs and/or spread to lymph nodes on the other side of the mediastinum as the tumor, or specific lymph nodes called scalenes or supraclavicular. Also, the patient may have tumor spread to the fluid surrounding the lung
4. Stage IV- the tumor has spread (metastasized) to other organs in the body outside the lungs (like the bones, brain or liver)

Stage IIIB and stage IV non small cell lung cancers are generally considered inoperable, so it is very important to know if the cancer has spread to lymph nodes on the opposite side of the chest as the tumor. Part of your workup to look for spread of the tumor (metastasis) will probably also entail CT scans of the liver and adrenals, a CT scan or MRI (a different sort of scan which uses magnets) of your brain, and a PET scan. If you are having particular symptoms, then your doctor may want different or more specific exams. Often times, if there is a plan for surgery, your doctor will order tests called PFT's (pulmonary function tests) to assess your lung capacity. Overall, your doctors will want to know as much about your particular tumor as possible so that they can plan the best available treatments.

What are the treatments for lung cancer?

Surgery

For patients with non small cell lung cancer, surgery is often employed in cancers up to and including stage IIIA. The purpose of the surgery is to remove all of the cancer if possible. If the tumor is small and in a favorable location, or the patient has limited lung function, the surgeon may choose to remove the tumor with a small section of lung; this is called a wedge resection. Most times the surgeon will choose to remove the entire lobe of the involved lung; this is known as a lobectomy. On occasion, the surgeon must remove the entire lung affected by the cancer; and this is known a pneumonectomy. Not every patient can tolerate these surgeries. Patients with diminished lung function due to other diseases may not be able to survive after such a surgery, or they may be severely limited in their activities. Preoperative pulmonary function tests (PFT's) are used to help predict who is a good candidate for surgery. Sometimes a quantified ventilation perfusion scan will be ordered which shows the amount that each area of lung is currently working. These tests may help the surgeon to predict how much lung function will be lost based on the amount of lung that will need to be removed, and how well the patient will feel after surgery. Surgery is not generally recommended for small cell lung cancer of any stage. Small cell lung cancer is usually treated with chemotherapy and radiation therapy. There have been some studies on the use of surgery in small cell lung cancer for very early stage lesions; however, this is not generally considered a standard option for patients with small cell lung cancer.

Another potential use for surgery with lung cancer lies in treating solitary brain or spinal metastases. If a patient has a solitary lesion in the brain or spine, a neurosurgeon may elect to remove them surgically. Talk with your doctor about the different ways to approach treatment of your particular disease.

Chemotherapy

Despite the fact that the tumors are often removed by surgery, there is always a risk of recurrence because there may be microscopic cancer cells left that the surgeon cannot remove. Also, some patients are not candidates for surgery or choose not to have surgery. Chemotherapy is the use of anti-cancer drugs that go throughout the entire body. These drugs may be given through a vein or as pills by mouth. Chemotherapy is recommended after surgery for some stage I and stage II non-small cell lung cancer patients. Because current treatment of advanced stage non-small cell lung cancers (stage III) is often a combination of radiation and/or chemotherapy and/or surgery, the timing and use of chemotherapy may vary depending on the specifics of the case. It may be given at the same time as radiation, or before or after radiation. Chemotherapy is offered to many patients with stage IV disease.

Small cell lung cancer is very responsive to chemotherapy, and most patients with small cell lung cancer will be offered chemotherapy. Again, depending on the specifics of an individual case, it may be given during radiation, or before or after radiation is complete.

There are many different chemotherapy drugs, and they are often given in combinations. Patients will usually have to go to a clinic to get the chemotherapy because many of the drugs have to be given through a vein. Different chemotherapy regimens are used for different purposes. Some of the drugs used in lung cancer chemotherapy include: Etoposide (and Teniposide), Cisplatin (and Carboplatin), Ifosfamide, Cyclophosphamide, Vincristine, Doxorubicin, Paclitaxel, Docetaxel,Gemcitabine (Gemzar ®) and Vinorelbine (Navelbine). There are advantages and disadvantages to each of the different regimens that your medical oncologist will discuss with you. Based on your own health, your personal values and wishes, and side effects you may wish to avoid, you can work with your doctors to come up with the best regimen for your cancer and your lifestyle.

Targeted Therapies/Biologic Therapies

Targeted (also called "biologic") therapies are a new class of medications that have been specifically designed to combat precise pathways in various cancers. Cancers have abnormal genetic pathways and receptors, and recent research has helped characterize the particular molecular pathways that make cells cancerous and resistant to treatment with chemotherapy and radiation. Sophisticated laboratory research and pharmaceutical design have created a new class of medications, known as targeted therapies. These medications often produce less significant side effects than standard chemotherapy drugs. They can be given both though a vein or as pills by mouth. They can also be given in combination with standard chemotherapy. Benefits in stage IV lung cancer patients have been recently reported using two different targeted therapies: "Bevacizumab (Avastin)" and "Erlotinib (Tarceva)". Clinical trials are ongoing to determine the benefit of other targeted therapies in this disease. For more information on targeted therapies see the Targeted Therapy Basics and Types of Targeted Therapies sections of Oncolink and talk to your doctor.

Radiotherapy

Lung cancer patients commonly are treated with radiation therapy. Radiation therapy uses high energy rays (similar to x-rays) to kill cancer cells. It comes from an external source, and it requires patients to come in 5 days a week for up to 6-8 weeks to a radiation therapy treatment center. The treatment takes just a few minutes, and it is painless. Radiation therapy is often combined with surgery and is important in the treatment of all types of lung cancer. It may be recommended before surgery to shrink a tumor to make it easier for the surgeon to remove. Radiation may be used after surgery if there are worrisome risk factors that make it likely for a tumor to come back in the chest. Sometimes radiation is used instead of surgery if a surgery is felt to be too dangerous for the patient, or if a tumor is too extensive to be removed with surgery.

Radiation is often used in the setting of metastatic disease (cancer cells that have spread to other regions of the body). Radiation can be used to reduce pain from metastatic disease, or reduce the risk of problems from cancer that may have spread to the brain.

In small cell lung cancer, brain radiation is sometimes used even if a patient does not have known cancer in the brain. This is called prophylactic cranial radiation. Clinical trials have shown that patients with small cell lung cancer may live longer if they have radiation to the brain; this is likely because cancer cells have spread to the brain, but tumor regions are too small to be seen with CT or MRI scans. Prophylactic cranial radiation can be used to kill these cells before they cause the patient problems.

Photodynamic Therapy

Photodynamic therapy (PDT) involves injecting a patient with a drug that preferentially gets taken up in cancer cells and then makes them sensitive to a particular kind of light. When the light is shone on the tumor, the drug is activated, and cancer cells are killed. Photodynamic therapy is occasionally used in the treatment of lung cancer for lesions in the airway. There are also clinical trials ongoing at the Hospital of the University of Pennsylvania to treat cancers with PDT that have spread to the fluid surrounding the lung cavity. Please visit the OncoLink/Emergingmed Clinical Trials Resource Center to see if you qualify for any of these studies.

Follow-up testing

Once a patient has been treated for lung cancer, he or she needs to be closely followed for a recurrence. At first, you will have follow-up visits fairly often. The longer you are free of disease, the less often you will have to go for checkups. Your doctor will tell you when he or she wants follow-up chest x-rays, CT scans, or other tests. Lung cancer is generally considered an aggressive tumor that often comes back after treatment; thus it is very important that you let your doctor know about any symptoms you are experiencing and that you keep all of your follow-up appointments. Finally, if you haven't yet done it, you need to quit smoking. Remember, it is never too late to get the health benefits of smoking cessation.

Clinical trials are extremely important in furthering our knowledge of this disease. It is though clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your doctor about participating in clinical trials in your area.

This article is meant to give you a better understanding of lung cancer. You may find this knowledge useful when meeting with your physician, making treatment decisions, and continuing your search for information. You can learn more about lung cancer on OncoLink through the related links to the left.

References

• Adjei, A.A., Marks, R.S., Bonner, J.A. (1999) Current Guidelines for the Management of Small Cell Lung Cancer. Mayo Clinic Proceedings, 74(8), 809-816
• The American Cancer Society All About Lung Cancer Overview www.cancer.org.
• Bunn, P.A. & Kelly, K. (2000) New Combinations in the Treatment of Lung Cancer: A Time for Optimism. Chest, 117(4) Supplement 1, 138S-143S
• Lippman, S.M. & Spitz, M.R. (2000) Lung Cancer Chemoprevention: An Integrated Approach. Journal of Clinical Oncology, 19(18S) Supplement, 74S-82S
• Marcus, P.M.(2000) Lung Cancer Screening: An Update. Journal of Clinical Oncology, 19(18S) Supplement, 83S-86S
• National Cancer Institute. What You Need To Know About Lung Cancer. www.cancer.gov.
• Rubin, P. and Williams, J.P., (Eds): Clinical Oncology: A Multidisciplinary Approach for Physicians and Students 8th ed. (2001). W.B. Saunders Company, Philadelphia, Pennsylvania.