Small-Cell Lung Cancer

Small cell lung cancer (SCLC) is one of the two major types of lung cancer. It is named because the cells appear small and round under the microscope.

Facts You Should Know About Small-Cell Lung Cancer

1. When cells of the lung start to undergo a degenerative transformation in appearance and start growing rapidly in an uncontrolled manner, the condition is called lung cancer. Lung cancer can affect any part of the lung. Lung cancer is the leading cause of cancer deaths in both women and men in the United States, Canada, and China. Two main lung cancer types exist small-cell lung cancer (SCLC, or small cell lung carcinoma, also formerly called oat cell cancer) and non-small-cell lung cancer (NSCLC). Most lung cancers are NSCLC, including squamous cell carcinoma and adenocarcinoma of the lung. Small-cell lung cancer accounts for only approximately 15% of all cases of lung cancer.
2. People should seek medical care when experiencing shortness of breath, unexplained weight loss, chest pain that doesn't go away or coughing up large amounts of blood.
3. Chemotherapy is the most effective treatment for small-cell lung cancer. Doctors may combine radiation therapy with chemotherapy for some patients.

Small-cell lung cancer differs from non-small-cell lung cancer in the following ways:

• Small-cell lung cancer grows rapidly. The time from the development of symptoms of SCLC to diagnosis is usually 90 days or less.
• Small-cell lung cancer spreads quickly. From 67%-75% of people who develop small cell lung cancer will have spread the SCLC outside of the lung to other parts of the body at the time of initial diagnosis.
• Small-cell lung cancer responds well to chemotherapy (using medications to kill cancer cells) and radiation therapy (using high-dose X-rays or other high-energy rays to kill cancer cells).
• SCLC is frequently associated with distinct paraneoplastic syndromes (collection of symptoms that may result from substances produced by the tumor, the effects of which can be general symptoms or at other parts of the body separate from those with direct cancer involvement).

People with SCLC typically have had symptoms for a relatively short time (8 to 12 weeks) before they visit their doctor.

The symptoms can result from local growth of the tumor, spread to nearby areas, distant spread, paraneoplastic syndromes, or a combination thereof.

Symptoms and signs due to local growth of the tumor include the following:

• New and persistent cough
• Coughing up blood
• Shortness of breath
• Chest pain made sometimes worse by deep breathing
• Wheezing

Symptoms and signs due to the spread of cancer to nearby areas include the following:

• Hoarseness of voice, resulting from compression (by cancer) of the nerve that supplies the vocal cords
• Shortness of breath, resulting from compression of the nerve that supplies the muscles of the diaphragm or severe shortness of breath, and stridor (sound produced by the turbulent flow of air through a narrowed part of the respiratory tract), resulting from compression of the trachea (windpipe) and larger bronchi (airways of the lung)
• Difficulty swallowing, resulting from compression of the esophagus (food pipe)
• Swelling of the face and hands, resulting from compression of the superior vena cava (the vein that returns deoxygenated blood from the upper body) restricting blood return.

Symptoms and signs due to distant cancer spread to other parts of the body depend on the site of spread and include the following:

• Spread to the brain can cause headaches, blurring of vision, nausea, vomiting, and weakness of any limb.
• Spread to the vertebral column can cause central back pain.
• Spread to the spinal cord can cause paralysis.
• Spread to the bone can cause bone pain.
• Spread to the liver can cause pain in the right upper part of the abdomen.

Symptoms and signs due to paraneoplastic syndromes include the following:

• Symptoms may or may not be characteristic of a specific organ system.
• Nonspecific symptoms include fatigue, loss of appetite, and weight loss.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a paraneoplastic syndrome that can occur with small-cell lung cancer or other cancers. Excessive levels of an antidiuretic hormone that lead to low blood sodium levels and nerve and muscular problems characterized by SIADH.

• The predominant cause of both small-cell lung cancer and non-small-cell lung cancer is tobacco smoking. However, smoking has a stronger link to small-cell lung cancer than non-small-cell lung cancer.
• Even secondhand tobacco smoke is a risk factor for SCLC and other types of lung cancer.
• All types of lung cancers occur with increased frequency in people who mine uranium, but small-cell lung cancer is most common. The prevalence increases further in people who smoke.
• Exposure to radon (an inert gas that develops from the decay of uranium) reportedly causes small-cell lung cancer.
• Exposure to asbestos increases the risk of lung cancer by nine times. A combination of asbestos exposure and cigarette smoking increases the risk by as much as 50 times.
• Exposure to arsenic, chromium, beryllium, nickel, soot or tar in the workplace is a risk factor for small-cell lung cancer.
• Exposure to diesel exhaust
• Other risk factors include HIV infection, living in an area of air pollution, having a family history of lung cancer, and being a heavy smoker along with taking beta-carotene supplements.

Consult a doctor if you are concerned that you might have cancer and specifically if any of the following symptoms and signs are present:

• Shortness of breath
• Chest pain
• Coughing up blood
• Unexplained weight loss
• Unexplained persistent fatigue
• Unexplained deep aches or pains

Go immediately to the nearest hospital emergency department if any of the following symptoms or signs are present:

• Coughing up large amounts of blood
• Chest pain that does not go away
• Sudden shortness of breath
• Sudden weakness of any limb
• Sudden vision problems

Initial examinations and tests for suspected lung cancer can include the following:

• Your health care provider will ask you questions about your medical, surgical, work, and smoking history.
• Physical examination to check for general signs of health
• Chest X-ray film
• Sputum cytology: Medical professionals examine cells in the sputum to see if they are cancerous.
• CT scan of the chest: An X-ray machine linked to a computer takes a series of detailed pictures of the inside of the chest from different angles. Other names of this procedure are computed tomography, computerized tomography, or computerized axial tomography. This modality is the standard for lung cancer screening and early detection.
• Thoracentesis: A sac encloses the lungs. Lung cancer can cause fluid to collect in this sac (pleural effusion). In people who have cancer, this fluid may contain cancer cells. A doctor removes the fluid with a needle and examines it for the presence of cancer cells. This fluid is usually visible on a chest X-ray.
• Bronchoscopy: This is a procedure used to look inside the trachea (windpipe) and large airways in the lung for abnormal areas. A doctor inserts a bronchoscope (a thin, flexible, lighted tube with a tiny camera on the end) through the mouth or nose and down the windpipe. From there, a doctor can insert it into the airways (bronchi) of the lungs. During bronchoscopy, the doctor looks for tumors and takes a biopsy sample (a sample of cells removed for examination under a microscope) from the airways.
• Biopsy: During a lung biopsy, a medical professional removes cancer cells so a pathologist can review them. Physicians use a fine-needle biopsy to remove tissues from the lung using a small, thin needle. This procedure is guided by a CT scan or ultrasound to help the physician place the needle in the right position.
• Mediastinoscopy: A doctor performs this procedure to determine the extent the tumor has spread into the mediastinum (area of the chest between the lungs). Mediastinoscopy is a procedure in which a doctor inserts a tube behind the breastbone through a small cut at the lowest part of the neck. Doctors take samples of the lymph nodes (small, bean-shaped structures found throughout the body) from this area to look for cancer cells.

Once a medical professional diagnoses a patient with lung cancer, examinations and tests are performed to find out whether cancer has spread (metastasized) to other organs of the person's body. These examinations and tests help to determine the stage of cancer. Staging is important because lung cancer treatment depends on the stage of cancer. Examinations and tests used to detect the spread of cancer may include the following:

• Blood tests: Complete blood count (CBC) (provides information about the type and count of different types of blood cells including anemia or signs of infection), serum electrolytes, renal function studies (for assessing kidney function), and liver function tests are all part of the routine tests for staging. In some cases, these tests may identify the site of metastasis. For instance, an elevated serum calcium level occurs with the spread of cancer to the bone. These tests are also important to assess the organ functions before starting treatment.
• CT scan of the brain, neck, abdomen, and pelvis to identify the possible spread of the cancer
• MRI of the brain and spine: MRI is an imaging technique used to produce high-quality images of the inside of the body. Medical professionals take a series of detailed pictures of areas inside the body from different angles. The difference between an MRI and CT scan is that MRI uses magnetic waves, whereas a CT scan uses X-rays for the procedure. Depending on the area to be studied and what the concerns are, one test might be better than the other.
• Radionuclide bone scan: With the help of this procedure, the doctor determines whether the lung cancer has spread to the bones. The doctor injects a minute quantity of radioactive material into the vein; this material travels through the bloodstream. If cancer spreads to the bones, the radioactive material collects in the bones. A doctor can then detect this with a scanner.
• PET scans differentiate limited disease confined to a single radiation field from the extensive metastatic disease at the time of initial diagnosis. Otherwise, PET scans are not used in the management of small-cell lung cancer.

Staging of small-cell lung cancer

Staging cancer provides important information about the outlook of the patient's condition and helps the doctor plan the best treatment. Although doctors stage other cancers from stage I to stage IV, small-cell lung cancer is classified into two stages.

• Limited stage: In this stage, the tumor is confined to a single radiation field. This includes the lung and the lymph nodes, within and between the lungs.
• Extensive stage: In this stage, cancer has spread from the lung to other organs of the body. This includes the presence of fluid in the lining of the lung (pleural effusion).

The most effective treatment for small-cell lung cancer is chemotherapy (using medications to kill cancer cells), either alone or in combination with radiation therapy (using high-dose X-rays or other high-energy rays to kill cancer cells).

Chemotherapy

Chemotherapy uses medications to kill cancer cells. Patients may take these medications by mouth (orally), but doctors usually inject them into a vein (IV).

Chemotherapy is a systemic treatment because the medications enter the bloodstream, travel throughout the body, and kill cancer cells wherever they are. However, some normal cells are also killed (causing some of the side effects of chemotherapy).

Doctors usually give chemotherapy at intervals to ensure that the bone marrow has recovered before the next dose of chemotherapy is given.

Extensive research and clinical trials have identified different chemotherapy medications in the last three decades for the treatment of lung cancer. Response rates with these medications are more than 80% in patients with small-cell lung cancer who were previously untreated.

While doctors use some medications alone, they use some in combination with others for greater effectiveness. An oncologist (cancer specialist) recommends chemotherapy specific to the patient's condition.

Chemotherapy medications used for the treatment of small-cell lung cancer include the following:

• Etoposide (Toposar, VePesid) is an effective antitumor medication. It slows or stops the growth of cancer cells in the body by causing breakage in the DNA (genetic material) strand. Doctors may give etoposide as an IV injection or as a pill.
• Cyclophosphamide (Cytoxan, Neosar) interferes with the growth of normal cells and cancer cells. It slows the growth of cancer cells and their spread in the body. Doctors may give cyclophosphamide as an IV injection or as a pill.
• Doxorubicin (Adriamycin, Rubex) causes the destruction of DNA, which slows or stops the growth and spread of cancer cells in the body. It is an IV medication.
• Vincristine (Oncovin) is a plant-based compound. It causes cell death by interfering with the way genetic material (DNA) multiplies in the cell. It is only available as an IV medication.
• Topotecan (Hycamtin) interferes with the growth of cancer cells by inhibiting the duplication of DNA. It is an IV medication.
• Paclitaxel (Taxol) interferes with the growth of cancer cells and slows their growth and spread in the body. It is an IV medication.
• Cisplatin (Platinol) is a platinum-based drug that causes breakage in the DNA (genetic material) strand and interferes with cell growth. It is an IV medication.
• Carboplatin (Paraplatin) is similar to cisplatin. It also causes breakage in the DNA (genetic material) strand and interferes with cell growth. Its effectiveness is similar to cisplatin, but people tolerate it better and it has lesser side effects.
• Irinotecan (Camptosar) acts similarly to topotecan to decrease cancer cell growth by causing damage to cancer cell DNA. It is an IV medication.

Rather than using a single agent therapy, combinations of drugs are most commonly used. Commonly used chemotherapy regimens in small-cell lung cancer include the following:

• PE (cisplatin or carboplatin and etoposide): This is the standard of care therapy in the United States.
• CAVE (cyclophosphamide, doxorubicin [Adriamycin], vincristine, and etoposide)
• PEC (paclitaxel, etoposide, and carboplatin)
• Topotecan alone, is used for people who have progressed on the initial therapy for small cell lung cancer
• Etoposide alone used orally primarily for elderly or infirm people
• Cisplatin and irinotecan: This is the standard of care therapy in Japan.
• CAV (cyclophosphamide, doxorubicin [Adriamycin], and vincristine): This is the old standard of care therapy for small cell lung cancer in the U.S.

Treatment of Limited-Stage Small-Cell Lung Cancer

• Currently, cisplatin, etoposide, vincristine, doxorubicin, and cyclophosphamide are the most commonly used medications for the treatment of people with small-cell lung cancer.
• Standard treatment of small-cell lung cancer involves combination chemotherapy with a platinum-based cisplatin-containing regimen. People repeat treatment cycles every 3 weeks. People generally receive treatment for four to six cycles.
• The combination of cisplatin and etoposide (PE) is the most widely used regimen in both limited- and extensive-stage small-cell lung cancer.
• More recently, paclitaxel and topotecan emerged as effective medications in people with small-cell lung cancer who have not been previously treated. The response rates range from approximately 40% with topotecan to 50% with paclitaxel.
• Some doctors start radiotherapy on the chest as early as possible, while others may give it with the fourth cycle of chemotherapy.
• Radiation and chemotherapy: Doctors may administer sequential-radiation treatment, followed by chemotherapy.
• If the patient is completely free of cancer, radiation therapy may be given to the patient's skull to reduce the risk of small-cell lung cancer spreading to his or her brain. This is called prophylactic cranial irradiation (PCI). It is usually given after the patient has completed the full chemotherapy and radiotherapy (to the thorax) regimen.

Treatment of Extensive-Stage Small-Cell Lung Cancer (Small-Cell Lung Cancer That Remains Incurable With Current Treatment Options)

• Combination chemotherapy treats people with extensive-stage small-cell lung cancer. Currently, the combination of cisplatin or carboplatin and etoposide (PE) is the most widely used regimen. In March 2019, the U.S. Food and Drug Administration approved the immune checkpoint inhibitor drug atezolizumab (Tecentriq) for the initial treatment of patients with extensive-stage small-cell lung cancer. The approval, which covers the use of the drug in combination with the chemotherapy drugs carboplatin and etoposide, was based on the results of a clinical trial that showed the addition of atezolizumab to the PE regimen helped patients live longer.
• Radiation therapy relieves the following symptoms:
  • Bone pain
  • Compression of the food pipe (esophagus), windpipe, or superior vena cava caused by tumors
  • If the person has a complete response or their extensive disease to chemotherapy, radiation may be offered to the chest to consolidate the response and to the brain to prevent metastasis is not present (prophylactic cranial irradiation).

Treatment of Relapse of Small-Cell Lung Cancer

• People who have a relapse of small-cell lung cancer have an extremely poor prognosis.
• If the disease does not respond to first-line treatment or progresses on initial treatment (for example, refractory disease) or if the disease relapses within six months of completion of therapy, the person has little chance of responding to additional chemotherapy.
• People whose cancer does not progress for more than 6 months may receive additional chemotherapy. These people may even be treated with the same chemotherapy regimen that resulted in the first remission.
• The immunotherapy drugs nivolumab (Opdivo) have been approved by the U.S. FDA for the treatment of advanced non-small-cell lung cancer in patients with recurrent advanced small-cell lung cancer who have already received chemotherapy.
• People with relapsed or refractory small-cell lung cancer may enroll in clinical trials. For information about ongoing clinical trials, visit the National Cancer Institute's Clinical Trials.

Doctors may give other drugs to prevent and treat adverse effects of radiation or chemotherapy, such as nausea or vomiting. Pain medications are also important to relieve pain due to cancer or surgery.

Radiation Therapy

Radiation therapy, which uses high-energy radiation to kill cancer cells, may be an option in some cases of small-cell lung cancer. It may be used to treat cancer itself or as a form of palliative treatment to reduce symptoms.

Immunotherapy

Immunotherapy uses a patient's immune system to target cancer cells. This is also referred to as biologic therapy because it involves the use of substances that stimulate the body's immune response. Immune checkpoint inhibitor therapy is a kind of immunotherapy that doctors use in advanced small-cell cancer. In this treatment, the checkpoint proteins (proteins on the surfaces of immune cells and cancer cells that keep immune responses in check) are blocked, meaning that the ability of the immune system to kill cancer cells is enhanced. There are currently two types of immune checkpoint inhibitor therapy:

• CTLA-4 inhibition: CTL4-A is a protein on the surface of T cells (a type of white blood cell involved in the immune response) that helps keep the body's immune responses in check. CTLA-4 inhibitors attach to CTLA-4 and allow the T cells to kill cancer cells. Ipilimumab (Yervoy) is a type of CTLA-4 inhibitor.
• PD-1 inhibition: PD-1 is another protein on the surface of T cells that helps keep the body's immune reaction in check. PD-1 attaches to another protein called PDL-1 and stops the T cell from killing the cancer cell. PD-1 inhibitor drugs attach to PDL-1 and allow the T cells to kill cancer cells. Pembrolizumab (Keytruda) and nivolumab (Opdivo) are types of PD-1 inhibitors.

Surgery plays little, if any, role in the management of small-cell lung cancer because almost all cancers have spread by the time they are discovered.

The exceptions are the relatively small number of people (<5%) whose cancer is discovered at a very early stage of the disease when the cancer is confined to the lung without any spread to the lymph nodes. Patients diagnosed with small-cell lung cancer at a very early stage of the disease may undergo surgical removal of the lung tumor as the initial diagnostic procedure. However, surgery alone is not curative, so chemotherapy, usually with radiation is also administered.

• Patients who are receiving chemotherapy require close monitoring for side effects and their response to therapy. The monitoring will include some general testing, as well as some that are specific to the agent used.
• Doctors need a blood workup, including CBC (complete blood count), prior to each cycle of chemotherapy to ensure that the bone marrow has recovered before the next dose of chemotherapy is given.
• Kidney function should be monitored, especially if the patient is taking cisplatin, as it can damage the kidneys.
• The hearing may need to be monitored for patients receiving cisplatin.
• Electrolytes need to be managed for patients on cisplatin, as cisplatin and carboplatin can cause a drop in serum magnesium, which can result in serious cardiac rhythm problems.
• A doctor may advise a patient to undergo a CT scan after two cycles of therapy to assess response to the therapy.

Palliative and Terminal Care

Because doctors most frequently diagnose small-cell lung cancer when it is not curable, palliative care becomes important. The goal of palliative and terminal care is to enhance the person's quality of life.

Doctors may give a patient radiation therapy as palliative treatment to relieve symptoms caused by compression of the food pipe, windpipe, or superior vena cava.

Palliative care offers the patient emotional and physical comfort and relief from pain. Palliative care not only focuses on comfort but also addresses the concerns of the patient's family and loved ones. The patient's caregivers may include family and friends in addition to doctors and other health care professionals.

Doctors often give palliative and terminal care in a hospital, hospice, or nursing home; however, it can also be provided at home.

Smoking cessation is associated with fewer respiratory infections and better lung function, especially in limited-stage small-cell lung cancer. Smoking cessation can be aided with the use of nicotine gum, medicated nicotine sprays or inhalers, nicotine patches, and oral medications including Chantix and bupropion. In addition, group therapy and behavioral training further increase the chances of quitting.

The success of treatment depends on the stage of small-cell lung cancer.

• The five-year survival rate for patients with stage I SCLC is 31%.
• In approximately 65%-70% of people with small-cell lung cancer, the disease has already spread to other organs of the body by the time small-cell lung cancer is diagnosed.
• The stage II SCLC survival rate is about 19%.
• People with small-cell lung cancer in the advanced stage cannot be cured. They usually survive less than one year.
• Treatment may be moderately successful for people with the limited-stage disease. However, even with the limited-stage disease, the median survival time is less than two years.
• The overall five-year survival rate for people with small-cell lung cancer is less than 20%.
• People with small cell lung cancer have the highest rate of developing a second primary cancer, usually in 5%-10% percent of cases but as high as 30%

Small-cell lung cancer is strongly associated with tobacco smoking. Smoking cessation and avoidance as well as avoidance of secondhand smoke can help lower your risk of developing lung cancer. Minimizing exposure to radon and asbestos will also reduce the risk.

Support groups and counseling can help you feel less alone and can improve your ability to deal with the uncertainties and challenges that cancer brings.

Cancer support groups provide a forum where patients with cancer, survivors of cancer, or both can discuss the challenges that accompany the illness and guide you to deal with your concerns.

Support groups provide an opportunity to exchange information about the disease, take advice about managing side effects, and share your feelings with others who are undergoing a similar situation.

Support groups also help your family and friends deal with the stress.

Many organizations offer support groups for people with cancer and their family members or friends of people who have cancer. You can get information about such groups from your doctor, nurse, or hospital social worker.

The following organizations can help you with support and counseling:

• The AMC Cancer Information and Counseling Line provides current medical information and counseling for cancer issues.
  800-525-3777
  [email protected]
• The Lung Cancer Alliance operates a national "phone buddies" program, in addition to other services.
  800-298-2436
  [email protected]
• The National Coalition for Cancer Survivorship is a survivor-led advocacy organization working exclusively on behalf of people with all types of cancer and their families.
  877-622-7937
  [email protected]

American Cancer Society
800-ACS-2345

American Lung Association
61 Broadway, 6th Floor
New York, NY 10006
800-LUNGUSA
800-586-4872

National Cancer Institute, Cancer Information Service
NCI Public Inquiries Office
6116 Executive Blvd
Suite 3036A
Bethesda, MD 20892-8322
800-4-CANCER
800-422-6237

American Society of Clinical Oncology
1900 Duke Street, Suite 200
Alexandria, VA 22314
703-299-0150

National Cancer Institute, Small Cell Lung Cancer: Treatment

American Medical Association, Atlas of the Body: The Respiratory System -- Basic Function

Lung Cancer Online

National Institutes of Health, National Cancer Institute