All About Small Cell Lung Cancer

What are the lungs?

The lungs are two spongy organs located in the chest. They deliver oxygen to the bloodstream. When you take a breath in, air moves into the lungs, causing them to expand (stretch). The air comes very close to blood that is traveling in small vessels called capillaries. The lungs are designed to place blood in close contact with as much air as possible, so their tissues are very delicate. When you breathe out, you exhale (breathe out) substances that you don't need, like carbon dioxide. The right lung has three sections, called lobes; the left lung has two lobes. 

You breathe in air through your mouth and nose. This air then travels down a tube, 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?

Cancer happens when cells grow in an uncontrolled way, which can lead to a tumor developing. Lung cancer occurs when cells in the lung begin to grow out of control. These cells can then spread to nearby tissues or throughout the body. Cells in any of the tissues in the lung can develop cancer.  Most commonly, lung cancer comes from the lining of the bronchi. Cancers are described by the type of cells they come from. Lung cancer is divided into two main categories:

• Small cell lung cancer (SCLC) - the rarer of the two types (about 15% of all lung cancers), small cell lung cancer can be more aggressive than non-small cell lung cancer because it 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 (80-85% of all lung cancers), non-small cell lung cancer is generally slower growing than small cell lung cancer. NSCLC is divided into different types based on how the cells look that make it up - adenocarcinoma, squamous cell carcinoma, and poorly differentiated or large cell carcinoma.

What causes lung cancer and am I at risk?

There are about 235,760 new cases of lung cancer diagnosed in the United States each year. The average age of diagnosis is 71. Lung cancer is slightly more common in men than women across all racial groups. Lung cancer is the most common cause of cancer deaths.

Smoking is the greatest risk factor for developing lung cancer. Other causes of lung cancer include exposure to radon, exposure to radiation, environmental exposure to particular chemicals, and previous lung diseases.

Smoking

Every smoker (current or former) is at risk for lung cancer. 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 no matter how long you have been smoking. In addition, giving up smoking decreases the chance of developing another lung cancer after treatment for the current cancer.

Those with lung cancer have been found to respond to treatment better and live longer if they quit smoking at the time of their diagnosis. If they continue to smoke, they can have a harder time getting through treatment, being at higher risk of side effects such as pneumonia and lung inflammation. This can result in needing to lower the chemotherapy doses a person receives, which can result in less effective therapy. 

Smoking also has an effect on people around you. Second-hand smoke or smoke inhaled when you are near someone smoking, is another risk factor for lung cancer. 

Smoking pipes and cigars is also a risk factor for lung cancer. Even though you are not inhaling, you are breathing the air that is filled with the smoke from these products. 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 how much marijuana and how often you smoke it seems to be related to your overall risk.

Radon

Radon is the second leading cause of lung cancer in the United States. Radon is a naturally occurring, odorless, colorless, radioactive gas that results from the decay of rock and soil components. Radon moves up from the ground into homes, where it becomes trapped and builds up. This exposes the residents to its cancer-causing potential. Different areas of the world have different amounts of radon produced. The type of foundation in your home is also important since some foundations are better ventilated. Because of this, two homes next door to each other could have different levels of radon in the indoor air.

Radon can build up in new and old homes and those with or without a basement. The only way to know if your home contains radon is to have it tested. This can be done using a kit from a hardware store or having a radon professional perform the test. Many areas have laws requiring radon testing before a house is sold. If radon is detected in levels above 4 pCi/L (picocuries per liter), you can have a removal system installed, which vents the gas to the outside using a pipe and fan system. 

Radiation Exposure

Radiation therapy used to treat a prior cancer that had the lungs in the treatment area increases the risk for developing a new cancer in that area of the lung. Such secondary cancers often take a decade or longer to develop. This can be seen in people treated for Hodgkin lymphoma and breast cancer, among others. Some guidelines suggest that Hodgkin lymphoma survivors have screening for lung cancers after treatment. Modern radiation equipment and planning reduces the exposure of healthy tissue and may reduce this risk.

Other Risk Factors

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 is even higher. Asbestos is found in industries like shipbuilding, 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 dust, talc, uranium, and gasoline and diesel exhaust fumes.

Electronic nicotine delivery systems (e-cigarettes) and hookah use are becoming more popular. At this time, there is no conclusive research stating that the use of e-cigarettes can cause lung cancer. However, the tiny particles in the aerosol of e-cigarettes can contain toxic chemicals that can penetrate into the lungs. Hookah use, and being exposed to hookah smoke, can cause serious health risks, including lung cancer. The tobacco used in a hookah is exposed to high heat from burning charcoal which is at least as toxic as cigarette smoke. The tobacco and toxic agents used in the hookah can be risk factors for lung cancer.

People who have already had lung cancer are at risk of getting it again. A history of interstitial lung disease, pulmonary fibrosis, or tuberculosis (TB) also increases your risk of getting lung cancer. Changes in your genes, both from the environment and some inherited from your parents can also increase your risk of lung cancer. 

Lung Cancer in Never Smokers

The number of cases of lung cancer in never smokers (people who have smoked less than 100 cigarettes in their lifetime) has been increasing in many countries, including the United States. Worldwide, never smokers make up 15-20% of new lung cancer cases in men, but 50% of new cases in women. Most lung cancers in never smokers are non-small cell lung cancers, as small cell lung cancer occurs almost exclusively in current or former smokers. This makes researchers think that lung cancer in never smokers may be a biologically different disease than in smokers.

The cause of these cancers is not clear, though the risk factors discussed above are all possibilities. Researchers are studying how these cancers may respond differently to targeted therapies aimed at specific molecular abnormalities and how smoking status could be used in treatment planning.

How can I prevent lung cancer?

The best way to prevent lung cancer is not to smoke or to quit if you already smoke. Avoid being around people who are smoking. Do not use pipes, cigars, hookahs, or smoke marijuana. Have your home tested for radon and install a removal system if needed. 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.

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 new imaging techniques may one day help decrease the risk of developing lung cancer.

What screening tests are available?

Lung cancer screening is not suggested for those at average risk of lung cancer. Those at higher risk should talk with their healthcare providers about the US Preventive Task Force recommendations for lung cancer screening. Screening is done with a low-dose CT (LDCT) scan of your chest. Testing may be recommended for you if: 

• You are between the ages of 50 to 80 and in fairly good health.
• You are currently are a smoker or have quit within the past 15 years.
• You have at least a 20-pack-year smoking history (you have smoked a pack a day for 20 years or 2 packs a day for 10 years).
• You will receive smoking cessation counseling if you are a current smoker.
• You have been involved in informed/shared decision making about the benefits, limitations, and harms of screening with LDCT scans.
• You have access to high-volume, high-quality lung cancer screening, and a treatment center. 

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).
• Chest pain.
• Shortness of breath.
• Coughing up blood or bloody phlegm.
• New hoarseness, wheezing, or changes in how your voice sounds.
• Pneumonia or bronchitis that keeps coming back.
• Weight loss.
• Loss of appetite.
• Fatigue (feeling more tired than usual).
• Bone pain, arm pain, new weakness.
• Dizziness or double vision.
• Numbness or tingling in your arms or legs.
• Neck or facial swelling.

You should see your healthcare provider if you are having any of these symptoms. Many of these symptoms can occur with other health conditions. 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 healthcare provider if their cough changes or gets worse.

How is lung cancer diagnosed?

If you have symptoms of lung cancer, usually you are referred for blood work and a chest x-ray and/or CT scan (a 3-D x-ray) of the chest. Your provider may order sputum cytology, which looks at your phlegm for cancer cells. To see if the lung cancer has spread outside of the chest (metastasis), you may have a CT scan of the abdomen (belly) and/or a PET-CT scan. To see if the lung cancer has spread to the brain, you may have an MRI or CT scan of the brain.

While all of these tests are important pieces of the puzzle, a biopsy is the only way to know for sure if you have cancer. A biopsy takes a sample of the suspicious area, which is then looked at under a microscope for any cancer cells. The biopsy is also necessary to determine the type of lung cancer and if there are cancer cells present in the lymph nodes.

A biopsy may be taken of the suspicious area in the lung and/or from lymph nodes near the lungs. Your provider will determine which areas should be biopsied and which biopsy method is best in your case. Biopsies are often done by a lung surgeon or a pulmonologist (a doctor specializing in lung diseases), who is trained in bronchoscopy. Possible methods for obtaining a biopsy include:

• Bronchoscopy: uses a thin, lighted tube placed down your nose or mouth and into your lung to look at the tumor and take samples of it. This can also be used to take samples of the lymph nodes. There are several bronchoscopy techniques that can be used. Your healthcare provider will determine which methods are best in your case based on the location of the lesion and if lymph nodes are being sampled.
• Needle biopsy: a needle is placed through the skin and between the ribs, and then into the tumor to get cells.
• Thoracoscopy: A surgical procedure where the surgeon inserts a small camera into the chest wall to look at the suspicious area, evaluate the extent of the tumor, and take biopsies.
• Video-assisted thoracoscopy or VATS: can be used for a biopsy or surgery in early-stage lung cancer; this technique is similar to thoracoscopy but requires fewer/smaller incisions, which may result in quicker recovery.
• Mediastinoscopy: A surgical procedure that uses a scope (camera on a tube), placed through the chest wall, to look at the suspicious area and take samples of lymph nodes to evaluate for the presence of cancer cells.

In some cases, tumor cells can get into the fluid around your lungs (called pleural fluid). Your healthcare provider may want to drain off some fluid by putting a needle into the space where the fluid has collected and examine that fluid under a microscope. This is called a thoracentesis.

Once the tissue is removed, a healthcare provider called a pathologist looks at the specimen under a microscope. The pathologist determines if it is cancer or not; and if it is cancerous, they will characterize it by:

• What type of tissue it came from.
• What subtype of lung cancer it is.
• How abnormal it looks (known as the grade).
• If it is invading surrounding tissues. 

The pathologist sends a pathology report to your healthcare provider, detailing their findings. This is an important piece in planning your treatment. You can request a copy of your report for your records.

Other tests done to help diagnose lung cancer include CT scans of the liver and adrenal glands (located above the kidneys), a CT scan or MRI of your brain, and a PET scan. These scans can tell us if the cancer has spread beyond the lungs (metastasis). 

Often, your doctor will order tests called PFT's (pulmonary function tests) to assess your lung capacity prior to considering surgery, radiation therapy, and some types of chemotherapy. 

If you are having particular symptoms, your provider may want different or more specific exams to determine their cause.

How is lung cancer staged?

After these tests are done, the stage of the cancer can be determined. Overall, your providers will want to know as much about your cancer and your health as possible so that they can plan the best available treatments. Clinical staging is done based on the size and location of the tumor on CT scans and PET scans, and if there is any evidence of spread to other organs that is picked up with radiology tests. The stage of the cancer affects how it is treated.

The staging system used to describe small cell lung cancer is the "TNM system,” as described by the American Joint Committee on Cancer. The TNM systems are used to describe many types of cancers. They have three parts: 

• T-describes the size/location/extent of the "primary" tumor in the lung.
• N-describes if the cancer has spread to the lymph nodes.
• M-describes if the cancer has spread to other organs (i.e.-metastases). 

Small cell lung cancer is grouped into two stages for treatment decisions:

• Limited-stage: stage I-III (T any, any N, M0) that can be safely treated with radiation therapy. Excludes T3-4 due to multiple lung nodules that are too extensive or have a size/area that is too large to be encompassed in a tolerable radiation plan.
• Extensive-stage: Stage IV (T any, N any, M1 a/b) or T3-4 due to multiple lung nodules that are too extensive or have a size/area that is too large to be encompassed in a tolerable radiation plan.

The staging system is very complex. The entire staging system is outlined at the end of this article. Though complicated, the staging system helps healthcare providers determine the extent of the cancer, and in turn, make treatment decisions for your cancer.

How is small-cell lung cancer treated?

Surgery

Most patients with SCLC have lymph node involvement or distant metastases when diagnosed. Surgery is a "local" treatment. This means it only treats the area taken out during the surgery. When cancer cells have already spread to areas outside of the lung, it is necessary to treat them with "systemic" therapy. This means one that can reach all areas of the body. This includes chemotherapy. Because the cancer has spread, surgery is not often used in SCLC.

The one exception to this is very early stage SCLC when there is no cancer found in lymph nodes. In these rare cases, surgery to remove the lobe of the lung containing the tumor, combined with other therapies like chemotherapy, is the preferred treatment for patients who are able to go through a surgical procedure.

Treatment for Limited Stage (LS-SCLC) Disease

Most SCLC responds well to chemotherapy. Most patients treated with chemotherapy will have a good response to initial treatment. Chemotherapy for limited-stage disease is often combined with radiation therapy. This combination has been shown to improve survival over chemotherapy alone. Unfortunately, most patients will ultimately develop resistance to chemotherapy and their disease can progress.

The timing and number of cycles of chemotherapy you receive will be determined by your healthcare team. Chemotherapies that may be used include cisplatin, etoposide and carboplatin. Chemotherapy can be given in combination with radiation therapy, which can be given once daily or twice (also called hyperfractionated) daily. Your specific plan will be determined by your care team. Radiation therapy is preferably given during the same time as chemotherapy is. It is ideally started as early after diagnosis as possible. However, in some cases, it may be preferable to give the radiation therapy after the chemotherapy is completed.

Treatment for Extensive Stage (ES-SCLC) Disease

As with limited-stage disease, extensive-stage SCLC is very sensitive to the effects of chemotherapy and the majority of patients treated with chemotherapy will have a good response to initial treatment. Unfortunately, most patients will ultimately develop resistance to chemotherapy and their disease can progress.

The timing and number of cycles you receive will be determined by your healthcare team. Some patients may benefit from receiving radiation therapy to the chest, which is given after completing chemotherapy. The chemotherapies used include carboplatin, etoposide, cisplatin, durvalumab, and irinotecan. 

Regardless of if the cancer is early or extensive stage, if the cancer returns in less than six months, other chemotherapy medications can be used. These include, topotecan, lurbinectedin, paclitaxel, docetaxel, irinotecan, temozolomide, cyclophosphamide, doxorubicin, vincristine, etoposide, vinorelbine, gemcitabine, and bendamustine.

Immunotherapy

Immunotherapy medications work with the immune system to kill cancer cells. Nivolumab is used to treat advanced SCLC that is no longer responding to other treatments such as chemotherapy. Atezolizumab and durvalumab can be used as a first line of treatment along with chemotherapy. 

Prophylactic Cranial Irradiation (PCI)

In both limited and extensive-stage SCLC, some patients may be offered treatment with "PCI" or prophylactic cranial irradiation. SCLC tends to spread to the brain, despite treatment with chemotherapy. Studies have found that patients treated with radiation therapy to the whole brain after completing chemotherapy have lower rates of brain metastases and improved survival rates. Patients who have had the cancer spread to the brain can also benefit from radiation therapy to the brain, with improved survival and quality of life.

Palliative Treatment

Often, SCLC has spread to other parts of the body by the time it is diagnosed. There are many options for palliative treatments for these areas of metastasis such as chemotherapy, radiation, surgery, stent placement, laser therapies, and removal of extra fluid from around the heart or lungs. Speak to your provider about your options for palliative treatment. 

Clinical Trials

Clinical trials are extremely important in furthering our knowledge of this disease. It is through clinical trials that we know what we do today, and many exciting new therapies are currently being tested. Talk to your healthcare provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service. 

Follow-up Care and Survivorship

Once you have been treated for lung cancer, you will need to be closely followed by your oncology team. During and shortly after treatment, you will be followed closely by your provider. How often you need to follow up will depend on the extent of your disease and your treatment plan. Often you will need a physical examination every 3-4 months for the first year and then every six months during year 2. Your healthcare providers will order chest imaging and bloodwork as indicated. If any new pulmonary nodules appear, your healthcare provider should initiate a workup for a new primary cancer. Routine PET/CT is not recommended for follow-up care.

Quitting smoking is important in lung cancer survivorship. Remember, it is never too late to get the health benefits of smoking cessation. If your family members smoke, it is a great opportunity to support each other and quit together. There are many programs to provide support in quitting as well as medications to support your efforts as well. Talk with your provider about these resources.

Fear of recurrence, relationship challenges, the financial impact of cancer treatment, employment issues, and coping strategies are common emotional and practical issues experienced by lung cancer survivors. Your healthcare team can identify resources for support and management of these practical and emotional challenges faced during and after cancer.

Cancer survivorship is a relatively new focus of oncology care. With nearly 17 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink.

Resources for More Information

Go2 Foundation for Lung Cancer

Provides support and advocacy for people living with lung cancer or at risk for the disease. 

https://go2foundation.org

Lungevity

Dedicated to changing outcomes for people with lung cancer through research, education, and support. 

lungevity.org

American Lung Association

Information on diagnosis, treatment, and support. 

www.lung.org/lung-disease/lung-cancer/

Free to Breathe

Funds research and advocates for improved treatments. Provides patients with treatment information. 

www.freetobreathe.org

Lungcancer.org

Professional oncology social workers provide free emotional and practical support for people with lung cancer, caregivers, and their loved ones; affiliated with CancerCare. 

www.lungcancer.org

Appendix: Complete Small Cell Lung Cancer Staging

American Joint Committee on Cancer 8th Edition, 2017