Small Cell Carcinoma

Small cell carcinoma is a rare, fast-growing type of cancer that most often develops in the lungs, though it can occasionally appear in other body sites. Strongly linked to tobacco smoking, this aggressive cancer tends to spread quickly throughout the body, but treatments can help many patients live longer and, in some cases, even lead to cure.

Table of contents

• What is small cell carcinoma?
• Types of small cell carcinoma
• How common is this condition?
• How small cell carcinoma affects the body
• Causes and risk factors
• Signs and symptoms
• Diagnosis
• Stages of small cell lung cancer
• Treatment options
• Prognosis and survival
• Prevention

What is small cell carcinoma?

Small cell carcinoma, also known as oat cell carcinoma, is a type of highly aggressive cancer that most commonly develops within the lung^[1][2]. The name comes from the appearance of the cancer cells under a microscope, which are smaller than typical cells and have a round to spindle shape with minimal surrounding fluid and rough chromatin^[3][6]. Because the cells can look like oats, the condition is sometimes called oat cell carcinoma^[1][3].

Small cell carcinoma is a neuroendocrine tumor, meaning that the cells were originally part of the body’s neuroendocrine system, which produces and releases hormones^[3]. As a result, small cell carcinoma often releases various hormones such as adrenocorticotropic hormone or vasopressin, which can cause additional symptoms beyond those from the cancer itself^[3].

When small cell carcinoma develops in the lungs, it is called small cell lung cancer. This cancer grows and spreads more rapidly than other types of lung cancer, with a shorter doubling time (the time it takes for the cancer to double in size), higher growth rate, and earlier development of spread to other parts of the body^[3][5].

Types of small cell carcinoma

There are two main types of small cell carcinoma, named for the types of cells found in the cancer and how they look under a microscope^[2][10]:

• Small cell carcinoma (also called oat cell cancer): This is the most common form of small cell lung cancer. It can grow and spread quickly, often leading to the cancer spreading to other parts of the body early in the disease process^[1][2][10].
• Combined small cell carcinoma: This is a rare type that represents about 2% to 5% of all small cell carcinomas. This type is a combination of small cell lung cancer cells and non-small cell lung cancer cells in the same tumor^[1][2][10].

While small cell carcinoma most often occurs in the lung, it can occasionally develop in other parts of the body, such as the cervix, prostate, or gastrointestinal tract^[3].

How common is this condition?

Small cell lung cancer is less common than non-small cell lung cancer. It accounts for approximately 15% of all lung cancer cases in the United States^[1][2][4][5]. Overall, about 57 in 100,000 people in the U.S. develop lung cancer, and small cell lung cancer represents about 15% of those cancer diagnoses^[1].

The overall number of people developing small cell lung cancer has decreased over the last four decades, reflecting decreases in smoking rates, changes to cigarettes, and reduced workplace hazards^[4]. Between 23,000 and 35,000 people are diagnosed with small cell lung cancer in the U.S. each year^[23].

When small cell lung cancer has spread extensively throughout the body, it is classified as a rare disorder^[3]. The ten-year relative survival rate (combining both limited and extensive stage small cell lung cancer) is 3.5%, with 4.3% for women and 2.8% for men^[3].

How small cell carcinoma affects the body

Small cell lung cancer starts when healthy cells in the lungs change or mutate into cancerous cells. These cells then divide and multiply uncontrollably. Eventually, the cancerous cells clump together in masses called tumors in the lungs^[1][12].

These tumors may shed cancer cells that your blood or lymph pick up and carry throughout your body. Lymph is fluid that travels through your body to your lymph nodes^[1][12].

Small cell lung cancer typically spreads to^[1][12]:

• Lymph nodes
• Bones
• Brain
• Liver
• Adrenal glands (glands located near the kidneys)

There is usually early involvement of the lymph nodes near the lungs and in the middle of the chest^[3]. Once the cells have spread, they may create new cancerous tumors in the lymph nodes and organs^[1][12].

Due to how quickly it grows and spreads, in 60% of small cell lung cancer cases the cancer has already spread to other areas in the body by the time it is diagnosed^[5]. When small cell lung cancer spreads to other parts of the body, the cancer can cause symptoms that are not typically associated with lung cancer, including bone pain, seizures, confusion, and paralysis^[5].

Small cell lung cancer may also cause fluid to build up in the lungs or in the space around the lungs. It can make the lung collapse by pushing air out of the lung. This is called a pleural effusion^[1][12].

Causes and risk factors

Smoking tobacco is the leading cause of small cell lung cancer, accounting for 85% of cases and responsible for 98% of all small cell lung cancer diagnoses^[4][5]. Small cell lung cancer is very strongly associated with tobacco smoking^[3]. While anyone can get lung cancer, people who smoke, used to smoke, or who are exposed to tobacco smoke (secondhand smoke) have a greatly increased risk of developing small cell lung cancer^[1][12].

Cigarette smoke contains many cancer-causing substances including polycyclic aromatic hydrocarbons, aromatic amines, N-nitrosamines, benzene, vinyl chloride, arsenic, and chromium, among many others. There is a relationship between how much smoke exposure a person has and their risk of lung cancer. The amount of smoke depends on the type of cigarette, how long the smoke is inhaled, and whether there is a filter^[4]. The risk for lung cancer among smokers is many times higher than among nonsmokers. The longer you smoke and the more packs per day you smoke, the greater your risk^[23].

It’s very rare for someone who has never smoked to have small cell lung cancer^[23].

Other risk factors for developing small cell lung cancer include^{[1][2][4][11][12][16]}:

• Exposure to cancer-causing substances in secondhand smoke
• Exposure to radiation from cancer treatments or imaging scans
• Radiation therapy to the breast or chest
• Exposure to radon gas (a colorless radioactive gas that may seep into homes and other buildings)
• Exposure to workplace hazards like asbestos, arsenic, chromium, beryllium, nickel, tar, or toxic chemicals
• Living in an area with air pollution
• Having a family history of lung cancer
• Having human immunodeficiency virus (HIV) infection
• Beta carotene supplements in heavy smokers
• Increasing age

Signs and symptoms

Small cell lung cancer that hasn’t spread rarely causes symptoms^[1][12]. Nearly 25% of lung cancer cases do not produce any symptoms^[5]. Lung cancer may present with symptoms or be found by chance on chest imaging^[11][16].

When symptoms do occur, they may include^{[1][2][5][10][12]}:

• Chronic cough that doesn’t go away or worsens
• Coughing up blood (hemoptysis)
• Chest pain or discomfort
• Difficulty breathing or shortness of breath
• Wheezing
• Hoarseness
• Facial swelling
• Swollen neck veins
• Fatigue
• Loss of appetite
• Unexplained weight loss

The most common symptoms at presentation are worsening cough and difficulty breathing^[11][16].

Symptoms may result from local invasion or compression of nearby structures in the chest. For example, compression involving the esophagus (food pipe) can cause difficulty swallowing, compression involving the laryngeal nerves can cause hoarseness, or compression involving the superior vena cava (a large vein) can cause facial swelling and distension of the superficial veins of the head and neck^[11][16].

Symptoms from cancer spread to distant parts of the body may also be present and include neurological problems or personality changes from brain spread, and pain from bone spread^[11][16].

Less commonly, patients with small cell lung cancer may present with symptoms and signs of paraneoplastic syndromes, which occur when the cancer releases hormones that affect other parts of the body. These can include^[11][16]:

• Inappropriate antidiuretic hormone secretion
• Cushing syndrome from secretion of adrenocorticotropic hormone
• Paraneoplastic cerebellar degeneration (affecting coordination and balance)
• Lambert-Eaton myasthenic syndrome (causing muscle weakness)

Many of these symptoms are similar to other less serious conditions. Having one or more of these symptoms isn’t a sign you have small cell lung cancer. That said, if you smoke or you used to smoke and you notice these types of symptoms, talk to a healthcare provider. They’ll evaluate your situation and recommend any next steps^[1][12].

Diagnosis

If lung cancer is suspected, your doctor will recommend several tests. Tests and procedures that examine the lungs are used to diagnose and stage small cell lung cancer^[2][10].

Your doctor will recommend imaging tests such as CT scans (computed tomography), PET scans (positron emission tomography), or MRI scans (magnetic resonance imaging) to identify abnormalities in and around your lungs^[5]. Your doctor may also take a sample of your mucus (sputum) to look for cancer cells^[5].

If these initial tests identify cancer, a biopsy can be performed. A biopsy means taking a small sample of tissue for examination. This can be done by either inserting a needle or making an incision in your chest to remove a small bit of tissue from your lung for further inspection^[5].

Another technique doctors commonly use to both visualize and remove lung tissue is called bronchoscopy. In this procedure, a thin tube with a camera is inserted through the mouth or nose into the airways^[5].

Looking at the cancer cells and noting their size and shape under a microscope gives your healthcare team helpful information about your diagnosis. It helps your care team figure out the type of cancer you have and where the cancer began. A careful study of the cancer cells can also show how much the cells have changed compared to healthy cells^[6].

Your doctor will also determine how far the small cell lung cancer has spread throughout your body. This descriptive process, called staging, can help inform treatment^[5].

Stages of small cell lung cancer

After small cell lung cancer has been diagnosed, tests are done to find out if cancer cells have spread within the chest or to other parts of the body^[2][10].

Small cell lung cancer has long been divided into two clinical stages, termed limited stage and extensive stage^[3][11][16].

The stage is generally determined by the presence or absence of spread to other parts of the body, whether or not the tumor appears limited to the chest, and whether or not the entire tumor burden within the chest can be treated with radiation therapy^[2][10].

Limited stage small cell lung cancer means that at the time of diagnosis, approximately 30% of patients have tumors confined to one side of the chest, the middle of the chest (mediastinum), or the lymph nodes above the collarbone (supraclavicular lymph nodes)^[11][16]. In general, if the tumor is confined to one lung and the lymph nodes close to that lung, the cancer is said to be limited stage^[5].

Extensive stage small cell lung cancer means that patients have tumors that have spread beyond the areas described for limited stage. If cancer has spread beyond the chest, it is said to be extensive stage^{[3][5][11][16]}. Due to how quickly it grows and spreads, 80-85% of patients present with extensive-stage small cell lung cancer at first diagnosis^[5].

Treatment options

If you have small cell lung cancer, your healthcare team will create a treatment plan just for you. It will be based on your health and specific information about the cancer. When deciding which treatments to offer, your healthcare team will consider whether the cancer is limited stage or extensive stage, your overall health, and your personal preferences^[15].

Current treatments include surgery, chemotherapy, radiation therapy, and immunotherapy^[4]. Various antibodies, including PD-1/PD-L1 inhibitors (immunotherapy drugs) and antibody-drug conjugates, have been introduced into clinical practice or are being evaluated in clinical trials^[13].

Chemotherapy

Small cell lung cancer is more responsive to chemotherapy and radiation therapy than other types of lung cancer^[11][16]. Small cell lung cancer often responds well to treatment with chemotherapy^[15].

Chemotherapy is most commonly treated with a combination of 2 drugs, which is more effective than one drug alone. The most common chemotherapy drug combinations used are cisplatin and etoposide, or carboplatin and etoposide^[15]. Etoposide-platinum is the current standard chemotherapeutic regimen^[13].

If you are in poor health, you may be given lower doses of chemotherapy. If you are not able to or do not want to have combination chemotherapy, etoposide may be given by mouth as a pill^[15].

Even though small cell lung cancer has a tendency to grow quickly, it often shrinks quickly in response to chemotherapy, radiation therapy, or both^[5]. Small cell lung cancer patients respond to chemotherapy initially, but most acquire resistance rapidly and relapse quickly^[13].

Radiation therapy

Most people with small cell lung cancer have radiation therapy^[15]. Radiation therapy uses high-energy rays to kill cancer cells. Your healthcare team will consider your personal needs to plan the type and amount of radiation, and when and how it is given^[15].

External beam radiation therapy uses a machine to direct radiation at the lung tumor and the surrounding lymph nodes in the chest. There are several different types of external radiation therapy used for small cell lung cancer, including 3D conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), stereotactic body radiotherapy (SBRT), and hypofractionated radiation therapy^[15].

Prophylactic cranial irradiation (PCI) is external beam radiation given to the whole brain. It may help prevent brain spread and improve survival. It is used when small cell lung cancer has responded well to chemotherapy and radiation therapy^[15].

Chemoradiation

Chemotherapy is often combined with radiation therapy to treat limited stage small cell lung cancer. This is called chemoradiation. The 2 treatments are given during the same time period. Chemoradiation is only offered if you are healthy enough to have both treatments at the same time^[15].

Immunotherapy

Anti-PD-L1 or anti-PD-1 antibodies have been used along with chemotherapy in the first-line treatment of small cell lung cancer and have improved overall survival, but the benefit is not significant^[13]. Immunotherapy has been efficacious against cancer in many other tumors^[13].

Surgery

Surgery may be used to diagnose and stage small cell lung cancer. But it is not used very often to treat small cell lung cancer because this type of cancer has usually spread to other parts of the body by the time it is diagnosed^[15]. Because of the high rate of spread, surgery is rarely recommended^[5].

In rare cases, surgery may be part of a treatment plan for limited stage small cell lung cancer that was found as a spot in the lung and that has not spread to the lymph nodes or outside the lung. You have to be healthy enough to have surgery^[15].

Other supportive treatments

Endobronchial therapies remove a blockage caused by the cancer inside the lung and help with symptoms such as problems with breathing, pain, or coughing up blood. They may also be used if you cannot have surgery or radiation therapy^[15].

In very advanced cases of small cell lung cancer, treatments (including chemotherapy and radiation) can be effective in relieving symptoms and improving quality of life^[5].

It is important to see a medical oncologist and radiation oncologist as soon as possible after a diagnosis of small cell lung cancer so that treatment can be started right away^[5].

Prognosis and survival

A cure is difficult to achieve because small cell lung cancer has a greater tendency to be widely disseminated (spread) by the time of diagnosis^[11][16]. However, healthcare providers can cure some people if the disease is found early; for others, they can help them live longer^[1][12].

Small cell lung cancer patients have a median progression-free survival (PFS) of approximately 5 months and an average overall survival (OS) of 12 months^[13]. Small cell lung cancer patients live for 7 months on average, but some patients have lived for 30+ years thanks to the treatments they received^[23].

Ten-year relative survival rate (combined limited and extensive small cell lung cancer) is 3.5% (4.3% for women, 2.8% for men)^[3]. Survival can be higher or lower based on a combination of factors including stage, age, sex, and race^[3].

Less than 7% of patients with extensive-stage small cell lung cancer survive 5 years past diagnosis^[5].

Certain factors affect prognosis (chance of recovery) and treatment options^[2][10].

Prevention

The only way to prevent small cell lung cancer is to stop smoking^[1][12]. The best preventive strategy is not to smoke, and if you do, to quit as soon as possible^[5].

Reducing the frequency of smoking is one of the main prevention methods for small cell lung cancer, and the ever-decreasing incidence confirms its effectiveness^[13].

Learning about risk factors for lung cancer can help you make changes that might lower your risk of getting it^[2][10]. Some risk factors for lung cancer, like smoking, can be changed. However, risk factors also include things you cannot change, like your genetics, age, and family history^[2][10].

• Lungs
• Bronchi (airways in the lungs)
• Lymph nodes
• Brain
• Liver
• Bones
• Adrenal glands

oat cell carcinoma, oat cell cancer, small cell lung cancer, SCLC