Following a neuroendocrine cancer diagnosis, a treatment plan is developed that may include the following options: 

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Active surveillance

Sometimes, active surveillance without any other treatment may be recommended. This approach is also called watchful waiting or watch-and-wait. It is used most often for someone with a low-grade NET that may grow slowly and not spread or cause problems for many months or years. If the tumor shows signs of growing or spreading, active treatment, such as surgery and/or therapies using medications (see below) may begin.  With active surveillance, your health and the tumor are closely monitored with regular tests, which may include:

• Imaging tests, usually computed tomography (CT) scans or sometimes magnetic resonance imaging (MRI) scans (see Diagnosis)

• Blood tests

• Physical examinations and evaluation of new symptoms

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Surgery

Surgery is the removal of the tumor and some surrounding healthy tissue during an operation performed by a surgical oncologist. Completely removing the entire tumor is the standard treatment, when possible.

Many located neuroendocrine cancers are successfully treated with surgery alone. The surgeon will usually remove some tissue surrounding the tumor, called a margin, in an effort to leave no traces of cancer in the body. When completely removing the tumor is not possible, "debulking surgery" is sometimes recommended. Debulking surgery removes as much of the tumor as possible and may provide some relief from symptoms, but it generally does not cure neuroendocrine cancer. 

 

People who have developed carcinoid syndrome are at risk to have a carcinoid crisis during surgery (see Neuroendocrine Cancer Symptoms). To avoid major complications from a carcinoid crisis, the anesthesiology team must be fully aware of this risk before surgery, so they can have treatment on hand to control the symptoms. Intravenous octreotide is usually given before surgery to prevent carcinoid crisis.  If removing a NET using surgery is not possible, it is called an “inoperable” tumor. In these situations, the doctor will recommend another treatment plan.

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Therapies with Medication

The treatment plan may include medications to destroy cancer cells. Medication may be given through the bloodstream to reach cancer cells throughout the body. When a drug is given this way, it is called systemic therapy. Medication may also be given locally, which is when the medication is applied directly to the cancer or kept in a single part of the body.  Medications can be given through an intravenous (IV) tube placed into a vein using a needle, in a pill or capsule that is swallowed (orally), or intramuscular (IM) injections.  Medications that may be used include:

• Somatostatin analogs

• Targeted therapy

• Peptide receptor radionuclide therapy (PRRT)

• Chemotherapy

• Immunotherapy

 

Medications may be given as part of a treatment plan that includes surgery and/or radiation therapy.

It is also important to let your doctor know if you are taking any herbs, supplements, and other drugs as these can interact with cancer medications resulting in unwanted side effects or reduced effectiveness. 

 

Somatostatin analogs

Somatostatin is a hormone in the body that controls the release of several other hormones, such as insulin and glucagon. Somatostatin analogs are drugs that are similar to somatostatin and are used to control the symptoms created by the hormone-like substances released by a NET. They may also slow the growth of a NET, although they do not generally shrink the tumors.

There are two types of somatostatin analogs used to treat neuroendocrine cancer: 

• Octreotide (Sandostatin), which is available as short-acting and given under the skin (subcutaneously); and long-acting, which is given as an intramuscular injection, and

• Lanreotide ,which is given as a long-acting subcutaneous injection.

The most common side effects are high blood sugar (hyperglycemia), the development of gallstones, and mild digestive system upset, such as bloating and nausea.

 

Targeted therapy

Targeted therapy is a treatment that targets the tumor’s specific genes, proteins, or the tissue environment that contributes to tumor growth and survival. This type of treatment blocks the growth and spread of tumor cells and limits damage to healthy cells.

Not all tumors have the same targets. To find the most effective treatment, your doctor may run tests to identify the genes, proteins, and other factors in your tumor. This helps doctors better match each patient with the most effective treatment whenever possible. In addition, research studies continue to find out more about specific molecular targets and new treatments directed at them. Learn more about the basics of targeted treatments.

• Everolimus (Afinitor) is a targeted therapy approved by the U.S. Food and Drug Administration (FDA) for the treatment of advanced NETs of the gastrointestinal (GI) tract, lung, and pancreas. This drug targets a protein called mTOR that is important for cell growth and survival. This drug can help slow down the growth of these tumors in some patients, but it does not usually shrink tumors. Side effects include mouth sores, lowering of blood counts, and fatigue.

• Sunitinib (Sutent) is a targeted therapy that targets a protein called VEGF. VEGF is important in angiogenesis, which is the process of making new blood vessels. Because a tumor needs the nutrients delivered by blood vessels to grow and spread, the goal of anti-angiogenesis therapies like sunitinib is to “starve” the tumor. It is approved by the FDA for the treatment of advanced pancreatic neuroendocrine cancer. Common side effects associated with this drug include diarrhea, nausea, vomiting, fatigue, and high blood pressure.

Other targeted therapies for neuroendocrine cancer are being researched in clinical trials. They include drugs that interfere with new blood vessel formation or with specific survival pathways of cancer cells.

 

Peptide receptor radionuclide therapy (PRRT)

In 2018, the FDA approved a treatment called 177Lu-dotatate (Lutathera) for advanced GI tract NETs and pancreas NETs. As a combined category, GI tract NETs and pancreas NETs are sometimes referred to as "GEP NETs." This treatment is also being studied for the treatment of other NETs. It is a radioactive drug that works by binding to a cell’s somatostatin receptor, which may be present on certain tumors. After binding to the receptor, the drug enters the cell, allowing radiation to damage the tumor cells. The broader term to describe this treatment is peptide receptor radionuclide therapy (PRRT).  Common side effects include low levels of white blood cells, high enzyme levels in some organs, nausea and vomiting, and fatigue. A rare, but serious side effect, is the development of blood cancer after the treatment.

 

Chemotherapy

Chemotherapy is the use of drugs to destroy cancer cells, usually by keeping the cancer cells from growing, dividing, and making more cells.  A chemotherapy regimen, or schedule, usually consists of a specific number of cycles given over a set period of time.  Chemotherapy for a NET may be used when the tumor has spread from where it started to other organs, if the tumor is causing severe symptoms, or if hormonal therapies or targeted therapies are no longer working. Chemotherapy may be used alone or in combination with other treatments.

 

The side effects of chemotherapy depend on the individual and the dose used, but they can include fatigue, risk of infection, nausea and vomiting, hair loss, loss of appetite, and diarrhea. Not all chemotherapies cause hair loss. These side effects usually go away after treatment is finished.

 

Immunotherapy

Immunotherapy uses the body's natural defenses to fight cancer by improving your immune system’s ability to attack cancer cells. Interferon alfa-2b (Intron A) is a type of immunotherapy that has been used in the past to treat NETs. Interferon helps the body’s immune system work better and can lessen diarrhea and flushing. It may also shrink tumors. This is treatment is not used very often nowadays due to newer FDA-approved treatments.

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Radiation therapy

Radiation therapy is the use of high-energy x-rays or other particles to destroy tumor cells. A radiation therapy regimen, or schedule, usually consists of a specific number of treatments given over a set period of time. A doctor who specializes in giving radiation therapy to treat cancer is called a radiation oncologist.

 

The most common type of radiation treatment for neuroendocrine cancer is called external-beam radiation therapy, which is radiation given from a machine outside the body. It is most often used as part of supportive care to relieve symptoms, such as pain, caused by cancer that has spread to the bone and other areas of the body (see “Physical, emotional, and social effects of a NET” below).

 

Patients receiving radiation therapy may experience fatigue during treatment, and the treated area may become red and dry. Radiation therapy to the chest or neck may cause a dry, sore throat or a dry cough. Some patients have shortness of breath during radiation therapy. Most side effects go away after the treatment is finished.

 

Liver-directed treatment

If cancer has spread to the liver, the treatments below may be used. These procedures are usually performed by an experienced interventional radiologist and may require an overnight hospital stay. Side effects include pain around the liver, fever, and higher levels of liver enzymes as measured by blood tests for a few days or weeks after treatment.

• Radiofrequency ablation (RFA). RFA destroys a tumor by heating it with an electric current. It is usually used for small liver metastases and does not work well on larger tumors.

• Hepatic artery embolization. This procedure blocks the tumor’s blood supply by sealing off the blood vessels leading to the tumor. If embolization is done by itself, it is called bland embolization. When combined with chemotherapy, it is called chemoembolization. When it is combined with radiation therapy, it is called radioembolization.

• It is not yet clear if one form of embolization treatment is more effective than the other. Although there are possible long-term side effects of radioembolization, so most centers that treat NETs select other treatment options. These treatments are usually used for people with metastatic disease that mostly affects the liver, in particular those who have symptoms caused by the size of the tumor or by hormones produced by the tumor.

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