Neuroendocrine small cell lung cancer: Stage 4 and more - Medical News Today

Neuroendocrine cells are specialized cells found in many parts of the body, including the gastrointestinal (GI) tract, gallbladder, and lungs.

These cells receive signals from the brain to produce and release certain hormones that control many of our body functions.

Neuroendocrine tumors (NETs) happen when neuroendocrine cells become overactive and cancerous. NETs usually involve the GI tract and the lungs.

Small cell lung cancer (SCLC), also called oat cell cancer, accounts for 10–15% of all lung cancers. It is also the most prevalent type of neuroendocrine lung tumor.

A color X-ray showing the blood vessels in a lung.Share on Pinterest
Coloured X-ray showing the blood vessels in a lung. Science Photo Library/Getty Images

Neuroendocrine lung tumors are a family of tumors that arise from the cells that line the bronchi and other parts of the lung.

This disease group has distinct clinical and pathological characteristics, and varies in cell structure, features, appearance, presence of dead cells (necrosis), and the number of dividing cells (mitotic index).

Typical carcinoid (TC)

TCs are low-grade, slow-growing tumors that rarely spread (metastasize) outside the lungs. This type of tumor has a good outlook. Management and treatment typically involve surgery. Smoking is not associated with TCs.

Atypical carcinoid (AC)

ACs are intermediate-grade tumors that commonly affect people who smoke. They grow faster and tend to spread to the bones and liver.

Small cell lung carcinoma (SCLC)

SCLC is the most common NET of the lungs. It is also the most aggressive. In 70% of people with SCLC, cancer has already spread to other areas by the time they receive a diagnosis. Smoking is the most significant risk factor for developing SCLC.

Large cell neuroendocrine carcinoma (LCNEC)

Like SCLC, LCNEC is also a fast-growing tumor. But it is not as common as SCLC. Smoking is also a major risk factor for developing LCNEC. LCNECs have cancerous cells that look similar to SCLC, but are larger.

Once a doctor makes a diagnosis, they determine how much the cancer has spread through staging. They may use the TNM staging system, which stands for tumor, node, and metastasis.

  • Tumor: Refers to the size of the tumor.
  • Node: Refers to the spread of cancer to nearby lymph nodes.
  • Metastasis: Refers to the spread of cancer to distant organs, such as the other lung, brain, or bones.

Stage 4, also called advanced stage, means that the cancer has spread. In stage 4, the tumor can be any size and may or may not have spread to nearby lymph nodes.

Stage 4 divides into two substages: 4A and 4B. 4A can mean any of the following:

  • The cancer is in both lungs.
  • Cancer cells are present in the lining surrounding the lung.
  • Cancer cells are present in the lining surrounding the heart.
  • The cancer has spread to a single area outside the chest, such as the lymph nodes or bones.

On the other hand, stage 4B means that cancer has spread to more than one area, in one or more organs.

Most doctors use a two-stage system when staging SCLC, dividing it into limited and extensive disease. Generally, extensive disease is the same as stage 4.

A 2021 article in the Annals of Oncology explains that people with carcinoids have a better outlook compared with those with SCLC and LCNEC. People who have carcinoids are also generally younger, and the disease is not strongly associated with smoking.

The 5-year relative survival rate for people with SCLC is 7%, compared with a 25% survival rate of those with non-small cell lung cancer (NSCLC).

Most people receive an SCLC diagnosis when the cancer has already spread extensively. A 2020 review notes that while people with SCLC tend to initially respond to chemotherapy, it is likely that they will go on to experience relapse, or the disease will progress.

A person with SCLC may have symptoms related to a localized lesion (in the lung or lungs) or distant metastases (cancer that has spread to other parts of the body). Symptoms of localized lesions typically involve airway obstruction. This is because the cancer is in one or both lungs, meaning it will affect a person's airway.

Symptoms may include:

As the disease progresses and spreads, people may experience other symptoms, such as weakness, weight loss, fever, paraneoplastic syndromes, anorexia, and pain.

SCLC may also cause sensory neuropathy, encephalomyelitis, and Lambert-Eaton syndrome.

Endocrine involvement may include Cushing's syndrome, hyperglycemia, hypoglycemia, syndrome of inappropriate secretion of antidiuretic hormone (SIADH), and hypercalcemia.

A majority of people with SCLC go to their doctor because they experience symptoms of the disease. Before doctors ask people to undergo tests, they will first perform a thorough physical exam and take a medical history.

Biopsy

If results suggest the possibility of lung cancer, doctors may ask a person to undergo several tests. To make a diagnosis, specialists extract lung cell samples and examine them in a lab.

These tests include:

  • Thoracentesis: During this procedure, a medical professional uses a hollow needle to extract fluid from around the lungs and check if they contain cancer cells.
  • Needle biopsy: During this procedure, a doctor removes tissue samples from a suspicious mass by passing a thin needle through it.
  • Bronchoscopy: During this procedure, a doctor uses a thin, flexible tube to check the airway for blockages. They may also do a biopsy during the procedure if they find a blockage or tumor.
  • Endobronchial ultrasonography (EBUS): EBUS uses ultrasound to visualize structures within and beside the central airways.
  • Open surgery: This procedure involves a surgical incision through the skin to get a sample from the tumor.

A pathologist will evaluate the samples and examine them under a microscope to check for the cell structure and appearance unique to SCLC.

Imaging techniques

Doctors can use several imaging techniques to help diagnose and monitor SCLC and other lung cancers. These include chest X-rays, CT scans, MRIs, bone scans, and PET scans.

The imaging techniques help identify suspicious masses or tumors, which may be cancers, and also help monitor cancer spread, response to treatment, relapse, and return of cancer.

Blood and urine tests

Doctors may also ask a person to undergo blood and urine tests to help with staging. Checking Ki67 levels can determine a person's tumor grade. A blood test can detect chromogranin-A, a protein that tumor cells produce. Urine tests can also detect serotonin, a hormone secreted by some NETs.

Treatment for SCLC depends on the cancer's aggressiveness and a person's health status.

People with limited-stage SCLC usually receive a combination of chemotherapy and chest radiation therapy. Surgery may also be an option in otherwise healthy individuals if the tumor is limited to one area. A person also receives chemotherapy after surgery.

Since brain metastasis is common, many people also receive radiation therapy to the head, called prophylactic cranial irradiation.

Surgery and radiation are not useful as initial treatments for extensive-stage SCLC. The standard of care for this condition is radiation and a combination of the chemotherapy drugs etoposide and cisplatin or carboplatin.

A 2020 review mentions that immunotherapy combined with chemotherapy is the new frontline of treatment for SCLC. This combination may significantly improve the overall outlook for people with extensive-stage SCLC.

Radiation therapy can also relieve symptoms caused by cancer growth in the lungs or when cancer has spread to other areas. People with poor health may benefit from low chemotherapy doses or supportive care to address complications and keep them as comfortable as possible.

Stage 4 neuroendocrine SCLC is the most common NET of the lung. Doctors often diagnose it when it has already spread.

Compared with other lung cancers, it has a poorer outlook. It is likely that a person will experience relapse even after their condition responds well to initial treatments.

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