Small Cell Lung Cancer Metastatic

Small cell lung cancer is an aggressive disease that spreads rapidly throughout the body. Around 70% of people receive their diagnosis when cancer has already spread to lymph nodes or other organs, making early detection and treatment critical to improving survival.

Table of contents

• What is small cell lung cancer?
• Understanding metastatic spread
• Risk factors
• Symptoms
• Complications and paraneoplastic syndromes
• Diagnosis
• Treatment options
• Outlook and prognosis

What is small cell lung cancer?

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

Small cell lung cancer (SCLC) is a type of cancer that begins in the neuroendocrine cells within the lungs^[1]. These cells receive messages from chemical messengers in the nervous system and respond by releasing hormones into the blood. Medical experts sometimes refer to SCLC as oat cell cancer because its oval-shaped cells appear similar to oat grains under a microscope^[1].

SCLC represents approximately 15% of all lung cancer cases in the United States^[1][2]. It is less common than non-small cell lung cancer, but it is more aggressive and fast-growing^[2][4].

• Lungs
• Bronchi (airways)
• Lymph nodes
• Liver
• Bones
• Brain
• Adrenal glands
• Bone marrow

There are two main types of small cell lung cancer. Small cell carcinoma (also called oat cell cancer) is the most common form and can grow and spread quickly, often leading to cancer spreading to other parts of the body early in the disease process^[4]. Combined small cell carcinoma is a rare subtype that has characteristics of both small cell lung cancer and non-small cell lung cancer in the same tumor, representing about 2% to 5% of all small cell carcinomas^[2][4].

Understanding metastatic spread

SCLC is an aggressive type of cancer with a remarkable ability to spread throughout the body. Compared with other solid tumors, SCLC has links to one of the highest concentrations of circulating cancer cells in the body^[1]. These are cancer cells that have left the tumor and travel through the bloodstream.

Around 70% of people who receive a diagnosis of SCLC already have cancer in the lymph nodes or other parts of the body at the time of diagnosis^[1]. Only one-third of individuals receive a diagnosis during the early stage of SCLC when the disease is more responsive to treatment^[1].

When small cell lung cancer starts, healthy cells in the lungs change into cancerous cells that divide and multiply uncontrollably. Eventually, the cancerous cells clump together in masses called tumors in the lungs^[2]. These tumors may shed cancer cells that blood or lymph fluid pick up and carry throughout the body^[2].

SCLC commonly spreads to the following sites in the body^[1][2]:

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

Once the cells have spread, they may create new cancerous tumors in lymph nodes and organs^[2]. Small cell lung cancer may also cause fluid to build up in the lungs or in the space around the lungs, which can make a lung collapse by pushing air out. This is called a pleural effusion^[2].

Among all solid tumors, small cell lung cancer has remarkable metastatic ability, with a majority of patients diagnosed with metastatic disease^[3]. In 60% of SCLC cases, the cancer has already spread to other areas in the body by the time it is diagnosed^[5].

Risk factors

The main risk factor for SCLC is tobacco use. Almost all people living with SCLC are current smokers or have a history of smoking^[1]. Smoking tobacco is the leading risk factor for SCLC, responsible for 98% of all SCLC diagnoses^[5]. People who smoke, used to smoke, or who are exposed to tobacco smoke (secondhand smoke) have an increased risk of developing small cell lung cancer^[2][4].

Exposure to the following may also increase a person’s risk of SCLC^[1][2]:

• Secondhand smoke
• Harmful chemicals such as arsenic, radon, and asbestos
• Pollution
• Radiation from cancer treatments or imaging scans
• Radon gas (a colorless radioactive gas that may seep into homes and other buildings)
• Workplace hazards like asbestos, arsenic, nickel, tar, or toxic chemicals

Other risk factors include having a family history of lung cancer and having human immunodeficiency virus (HIV)^[2].

Symptoms

Symptoms of SCLC can vary from person to person. There are rarely any noticeable symptoms early in the course of the disease^[1]. Small cell lung cancer that hasn’t spread rarely causes symptoms^[2]. Signs and symptoms depend on the size and location of the tumor and typically appear 8 to 12 weeks before someone seeks medical attention^[1].

Common symptoms include^[1][2]:

• Cough that doesn’t go away or gets worse over time
• Coughing up blood
• Wheezing
• Chest pain or discomfort that worsens when coughing or taking a deep breath
• Hoarseness
• Loss of appetite
• Unintended weight loss
• Fatigue
• Recurrent lung infections, such as bronchitis and pneumonia
• Difficulty breathing or shortness of breath
• Facial swelling
• Swollen neck veins

SCLC commonly spreads to the brain, liver, bone marrow, and adrenal glands. Additional symptoms depend on the affected areas and the extent of the disease^[1]. They may include:

• Bone pain
• Jaundice (a yellowing of the skin and eyes)
• Headaches
• Dizziness
• Double vision
• Seizures
• Numbness or tingling in the hands or feet
• Small lumps on the skin

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^[2]. That said, if you smoke or you used to smoke and you notice these types of symptoms, talk to a healthcare provider.

Complications and paraneoplastic syndromes

Among solid tumors, SCLC is the most common cause of paraneoplastic syndromes^[1]. These rare disorders arise due to an unusual immune system response to cancer. They can also develop due to the unusual production of hormones^[1].

People may present with symptoms of paraneoplastic syndromes, a rare complication in response to cancer or unusual hormone production^[1]. The most common paraneoplastic syndrome in SCLC is syndrome of inappropriate antidiuresis, which affects how the body handles fluids^[1].

Diagnosis

If lung cancer is suspected, a doctor will recommend imaging tests such as CT scans, PET scans, or MRI scans to identify abnormalities in and around the lungs^[5]. A doctor may also take a sample of mucus to look for cancer cells^[5].

If these initial tests identify cancer, a biopsy can be performed by either inserting a needle or making an incision in the chest to remove a small bit of tissue from the lung for further inspection^[5]. Another technique doctors commonly use to both visualize and remove lung tissue is called bronchoscopy^[5].

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^[4]. A doctor will also determine the extent to which the SCLC has spread throughout the body. This descriptive process, called staging, can help inform treatment^[5].

Although numerical stages are used for SCLC as well as for other cancers, SCLC is often classified as either limited-stage, where the cancer is confined to a reasonable radiation field within the chest, or extensive-stage, where the cancer has spread beyond the chest^[5].

Treatment options

The main treatments for small cell lung cancer include chemotherapy, radiation therapy, immunotherapy, and in rare cases, surgery^[5][8]. You may have one or more of these treatments depending on the stage of the cancer and how well the treatment works^[8].

Chemotherapy and immunotherapy

The most common treatment for small cell lung cancer is chemotherapy^[5][8]. The standard chemotherapeutic regimen is etoposide-platinum^[5]. SCLC patients respond to chemotherapy initially, but most acquire resistance rapidly and relapse quickly^[5].

Beginning in 2019, immunotherapy was added as part of the first-line treatment for extensive-stage small cell lung cancer^[9]. The immunotherapy drugs atezolizumab and durvalumab block the protein PD-L1 and boost the body’s immune response to cancer cells. When used in combination with chemotherapy, these drugs increased overall survival and progression-free survival from chemotherapy alone^[9].

In May 2024, the Food and Drug Administration granted accelerated approval to tarlatamab-dlle (Imdelltra) for extensive stage small cell lung cancer with disease progression on or after platinum-based chemotherapy^[9]. This injectable medicine is an antibody that targets a protein on cancer cells. By attaching to this protein, tarlatamab helps the body’s immune system find and destroy the cancer cells^[9].

Radiation therapy

Radiation therapy is commonly used for SCLC treatment^[5][8]. If you are fit enough, you might have chemotherapy at the same time as radiation therapy, which is called chemoradiotherapy^[8].

Even though SCLC has a tendency to grow quickly, it often shrinks quickly as a response to chemotherapy, radiation therapy, or both^[5]. It is important to see a medical oncologist and radiation oncologist as soon as possible after a diagnosis of SCLC so that treatment can be started right away^[5].

Surgery

Because of the high rate of spread to other parts of the body, surgery is rarely recommended for SCLC^[5]. If cancer is at a very early stage, you might be able to have surgery to remove the affected part of the lung^[8].

Radiation to the brain

Some patients may receive radiation therapy to the brain, called prophylactic cranial irradiation or PCI^[8]. This treatment is given to prevent cancer from spreading to the brain in patients who have responded well to initial treatment.

Treatment for recurrent disease

In 2020, the FDA approved the chemotherapy drug lurbinectedin (Zepzelca) to treat metastatic SCLC that has progressed after other treatments^[9]. In February 2021, the FDA approved the drug trilaciclib (Coasela) for patients with extensive-stage SCLC undergoing chemotherapy^[9]. Trilaciclib limits the damage chemotherapy causes to bone marrow, making patients less susceptible to fatigue and infection and less likely to need rescue interventions during treatment^[9].

Outlook and prognosis

Small cell lung cancer has associations with more negative outcomes due to how rapidly it grows and spreads early^[1]. SCLC patients have a median progression-free survival of approximately 5 months and an average overall survival of 12 months^[5]. However, some patients have lived for 30 or more years thanks to the treatments they received^[5].

Healthcare providers can cure some people if the disease is found early. For others, they can help them live longer^[2]. The outlook for patients with metastatic small cell lung cancer depends on several factors, including the extent of disease spread, how well the cancer responds to treatment, and the person’s overall health^[1].

Although there are additional therapies for patients whose cancer comes back, their response to further therapies is substantially reduced^[5]. There is an urgent need to find more effective therapies to prolong patient survival^[5].

Thanks to forward-thinking innovations, patients with metastatic lung cancer are living longer than they did 10 years ago^[5]. Research continues to ensure that more patients with metastatic lung cancer can look forward to even longer lives^[5].