Neuroendocrine Tumor of the Gastrointestinal Tract: Types of Treatment

Approved by the Cancer.Net Editorial Board, 07/2022

ON THIS PAGE: You will learn about the different types of treatments doctors use for people with a neuroendocrine tumor of the gastrointestinal tract (GI tract NET). Use the menu to see other pages.

This section explains the types of treatments, also known as therapies, that are the standard of care for a GI tract NET. “Standard of care” means the best treatments known. Information in this section is based on medical standards of care for a GI tract NET in the United States. Treatment options can vary from one place to another.

When making treatment plan decisions, you are also encouraged to discuss with your doctor whether clinical trials offer additional options to consider. A clinical trial is a research study that tests a new approach to treatment. Doctors learn through clinical trials whether a new treatment is safe, effective, and possibly better than the standard treatment. Clinical trials can test a new drug, a new combination of standard treatments, or new doses of standard drugs or other treatments. Clinical trials are an option for all stages of cancer. Your doctor can help you consider all your treatment options. Learn more about clinical trials in the About Clinical Trials and Latest Research sections of this guide.

How a GI tract NET is treated

In cancer care, different types of doctors who specialize in cancer, called oncologists, often work together to create a patient’s overall treatment plan that combines different types of treatments. This is called a multidisciplinary team and is especially important for people with a NET. Your team may include different types of oncologists, which are doctors who specialize in cancer, a gastroenterologist, or GI doctor, who specializes in the digestive system, and other physicians. Cancer care teams include other health care professionals, such as physician assistants, nurse practitioners, oncology nurses, social workers, pharmacists, counselors, dietitians, physical therapists, occupational therapists, and others. Learn more about the clinicians who provide cancer care.

Treatment options and recommendations depend on several factors, including the stage and grade of cancer, possible side effects, and the patient’s preferences and overall health. Take time to learn about all of your treatment options and be sure to ask questions about things that are unclear. Talk with your doctor about the goals of each treatment and what you can expect while receiving the treatment. These types of conversations are called “shared decision-making.” Shared decision-making is when you and your doctors work together to choose treatments that fit the goals of your care. Shared decision-making is important for a GI tract NET because there are different treatment options. Learn more about making treatment decisions.

The common types of treatments used for a GI tract NET are described below, followed by an outline of treatment options by stage. Your care plan may also include treatment for symptoms and side effects, an important part of cancer care.

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Active surveillance

Active surveillance, which is also called watchful waiting or watch-and-wait, may be recommended sometimes. This approach is used most often for low-grade NETs that may grow slowly and not spread or cause problems for many months or years. With this approach, the tumor is closely monitored with regular tests, which may include:

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

  • Blood tests

  • Physical examinations

Active treatment usually only begins if the tumor shows signs of growing or spreading.

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Surgery

Surgery is the removal of the tumor and some surrounding healthy tissue during an operation. A surgical oncologist is a doctor who specializes in cancer surgery.

Completely removing the entire tumor is the standard treatment for a GI tract NET, when possible. Most localized GI tract NETs 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 a NET. Debulking surgery may be recommended if the tumor has spread to other parts of the body, called metastatic disease. If no surgery is possible, it is called an “inoperable” or "unresectable" tumor. In these situations, the doctor will recommend another type of treatment.

People who have carcinoid syndrome are at risk of experiencing a carcinoid crisis during surgery and other procedures (see Symptoms and Signs). 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. This treatment is usually a somatostatin analog.

Before surgery, talk with your health care team about the possible side effects from the specific surgery you will have. Learn more about the basics of cancer surgery.

Surgical options for a GI tract NET include:

  • Local excision. During this operation, the surgeon removes the tumor and some surrounding healthy tissue. Most localized tumors can be surgically removed through a skin incision. A rectal NET may be removed through the anus. Other GI tract NETs can sometimes be removed using an endoscope (see Diagnosis).

  • Partial gastrectomy. This surgery removes part of the stomach.

  • Esophagectomy. This procedure is the removal of all or part of the esophagus. The esophagus is the tube that connects the throat to the stomach.

  • Small bowel resection. The small bowel is another term for the small intestine. This surgery removes parts of the small intestine.

  • Appendectomy. Appendectomy is surgery to remove the appendix.

  • Segmental colon resection or hemicolectomy. This surgery removes one-third to one-half of the colon, including nearby blood vessels and lymph nodes.

  • Low anterior resection. During this surgery, a portion of the upper part of the rectum is removed.

  • Abdominoperineal resection. This surgery is used for a large tumor located in the lower part of the rectum. During the operation, the surgeon removes the anus, rectum, and part of the colon. After surgery, a colostomy may be created to carry waste out of the body. A colostomy is an opening from the colon to the outside of the body.

  • Liver resection. This operation removes cancer that has spread to the liver. The goal of this surgery is not to eliminate the cancer, but it often helps relieve or reduce the symptoms of carcinoid syndrome.

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Therapies using medication (updated 12/2023)

The treatment plan may include medications to destroy tumor cells. When these medicines are given by mouth, through the bloodstream, or as an injection into the muscle or underneath the skin, these are called "systemic therapies" because they reach tumor cells throughout the body. This treatment is generally prescribed by a medical oncologist, a doctor who specializes in treating cancer with medication. If you are given oral medications to take at home, be sure to ask your health care team about how to safely store and handle them.

The types of medications used for a GI tract NET include:

  • Somatostatin analogs (octreotide or lanreotide)

  • Chemotherapy

  • Targeted therapy

  • Peptide receptor radionuclide therapy (PRRT)

  • Immunotherapy

Each of these types of therapies is discussed below in more detail. A person may receive 1 type of medication at a time or a combination of medications given at the same time. They can also be given as part of a treatment plan that includes surgery and/or radiation therapy.

The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications.

It is also important to let your doctor know if you are taking any other prescription or over-the-counter medications or supplements. Herbs, supplements, and other drugs can interact with cancer medications, causing unwanted side effects or reduced effectiveness. Learn more about your prescriptions by using searchable drug databases.

Somatostatin analogs

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

68Ga DOTATATE or 64Cu DOTATATE PET scans (see Diagnosis) are used to determine whether a somatostatin analog will be part of the treatment plan.

There are 2 somatostatin analogs currently used to treat NETs:

  • Octreotide is available in 2 forms. Short-acting octreotide is given under the skin (subcutaneous) and long-acting is given as an injection into the muscle (intramuscular or IM).
  • Lanreotide is given as a long-acting subcutaneous injection.

The most common side effects of somatostatin analogs are high blood sugars, the development of gallstones, and mild digestive system upset, such as bloating and nausea. Talk with your doctor about what to expect and how side effects will be managed.

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Chemotherapy

Chemotherapy is the use of drugs to destroy cancer cells, usually by keeping the cancer cells from growing, dividing, and making more cells. Chemotherapy for a GI tract NET is most often used when the tumor has spread to other organs or is causing severe symptoms.

A chemotherapy regimen, or schedule, usually consists of a specific number of cycles given over a set period of time. A patient may receive 1 drug at a time or a combination of different drugs given at the same time. Common drugs for a GI tract NET include:

  • Capecitabine (Xeloda) and oxaliplatin (Eloxatin), which is a combination called CAPEOX.
  • Fluorouracil (5-FU) can also be used with oxaliplatin, which is a combination called FOLFOX.
  • Carboplatin or cisplatin combined with etoposide, all available as generic drugs, given intravenously. This regimen is usually used only for poorly differentiated disease (carcinomas) or very rapidly progressing well-differentiated grade 3 NETs.

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.

Learn more about the basics of chemotherapy.

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Targeted therapy

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

The U.S. Food and Drug Administration (FDA) has approved everolimus (Afinitor) for the treatment of advanced GI tract NETs. This treatment can help slow down the growth of these tumors in some people, but it does not usually shrink tumors. Side effects include mouth sores, lowered blood counts, and fatigue. Talk with your doctor about possible side effects and how they can be managed.

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

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Peptide receptor radionuclide therapy (PRRT)

A treatment called 177Lu-dotatate (Lutathera) may be used to treat advanced GI tract NETs. The broader term to describe this treatment is peptide receptor radionuclide therapy (PRRT). This is a radioactive drug that works by binding to a tumor cell’s somatostatin receptors, which may be present on certain tumors. After binding to the receptors, the drug enters the cell, allowing radiation to damage the tumor cell.

Common side effects include low levels of white blood cells, red blood cells, and platelets; high blood sugar levels; nausea and vomiting; and fatigue. Talk with your doctor about ways these can be avoided or managed. There are also rare but serious risks of kidney problems and secondary blood cancers, such as myelodysplastic syndrome and leukemia. Other types of PRRT for GI tract NETs are being studied in clinical trials. 

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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 to treat NETs, but it is not currently recommended.

Learn more about the basics of immunotherapy.

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Radiation therapy

Radiation therapy is the use of high-energy x-rays or other particles to destroy cancer 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 a GI tract NET is called external-beam radiation therapy, which is radiation given from a machine outside the body. There are multiple forms of external-beam radiation therapy, such as stereotactic body radiotherapy (SBRT), which is also called stereotactic ablative radiotherapy (SABR). It is most often used as part of supportive care to relieve symptoms, such as pain, that are caused by cancer that has spread to the bone and other areas of the body (see “Physical, emotional, and social effects of cancer,” 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 sore throat, dry cough, or shortness of breath. Most side effects go away after the treatment is finished. Learn more about the basics of radiation therapy.

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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 any form of embolization treatment is more effective than the other. Ongoing clinical trials are evaluating and comparing different types of embolization. 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. If this treatment is recommended for you, talk with your doctor about possible side effects and how they can be managed.

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Physical, emotional, social, and financial effects of a NET

A NET and its treatment cause physical symptoms and side effects, as well as emotional, social, and financial effects. Managing all of these effects is called palliative and supportive care. It is an important part of your care that is included along with treatments intended to slow, stop, or eliminate the tumor.

Palliative and supportive care focuses on improving how you feel during treatment by managing symptoms and supporting patients and their families with other, non-medical needs. Any person, regardless of age or type and stage of tumor, may receive this type of care. And it often works best when it is started right after a diagnosis. People who receive palliative and supportive care along with treatment for the tumor often have less severe symptoms, better quality of life, and report that they are more satisfied with treatment.

Supportive treatments vary widely and often include medication, nutritional changes, relaxation techniques, emotional and spiritual support, and other therapies. You may also receive palliative treatments, such as chemotherapy, surgery, or radiation therapy, to improve symptoms.

For some people, such as those with lung disease, heart disease, or other specific medical conditions, surgery cannot successfully treat the tumor. In these cases, palliative surgery to relieve symptoms may be helpful. Palliative surgery is often used together with radiation therapy.

Before treatment begins, talk with your doctor about the goals of each treatment in the recommended treatment plan. You should also talk about the possible side effects of the specific treatment plan and palliative and supportive care options. Many patients also benefit from talking with a social worker and participating in support groups. Ask your doctor about these resources, too.

Medical care is often expensive, and navigating health insurance can be difficult. Ask your doctor or another member of your health care team about talking with a financial navigator or counselor who may be able to help with your financial concerns.

During treatment, your health care team may ask you to answer questions about your symptoms and side effects and to describe each problem. Be sure to tell the health care team if you are experiencing a problem. This helps the health care team treat any symptoms and side effects as quickly as possible. It can also help prevent more serious problems in the future.

Learn more about importance of tracking side effects in another part of this guide. Learn more about palliative and supportive care in a separate section of this website.

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Treatment by stage of a GI tract NET

Different treatments may be recommended for each stage of a GI tract NET. The general options by stage are described below. For more detailed descriptions, see "How a GI tract NET is treated," above. Your doctor will work with you to develop a specific treatment plan based on your specific diagnosis and needs. Clinical trials may also be a treatment option for each stage.

Stages I, II, and III

  • Stomach. A localized NET of the stomach can often be completely removed through an endoscope. A tumor larger than 2 cm is removed with a margin of surrounding stomach tissue through an incision, or cut, in the abdomen. Treatment plans for NETs of the stomach also depend on whether they are associated with the secretion of gastrin and if an endoscopy finds inflammation of the stomach cells, called atrophic gastritis. This information helps determine the specific subtype of the tumor: type 1, 2, or 3. This can be a complicated diagnosis, and it is important to work closely with your doctor on selecting the best treatment.

  • Small intestine/large intestine (colon). Surgery to remove the tumor, surrounding tissue, and lymph nodes is the most common treatment for a NET in the small and large intestine.

  • Appendix. An appendectomy is usually the only treatment needed for a NET smaller than 2 cm. For a tumor larger than 2 cm, the removal of about one-third of the colon next to the appendix and nearby blood vessels and lymph nodes is often needed.

  • Rectum. A rectal NET smaller than 1 cm is often removed with an endoscopy. A tumor larger than 1 cm is usually removed using the same surgical procedure that is used for rectal cancer. This involves removing some healthy colorectal tissue and some of the nearby lymph nodes.

Stage IV (updated 12/2023)

If a NET spreads to another part in the body from where it started, doctors call it stage IV or metastatic cancer. If this happens, it is a good idea to talk with doctors who have experience in treating it. Doctors can have different opinions about the best standard treatment plan. Clinical trials might also be an option. Learn more about getting a second opinion before starting treatment, so you are comfortable with your chosen treatment plan.

Your treatment plan may include a combination of the treatments described above. Your doctor will recommend treatments based on several factors, such as the grade of the tumor, the degree of differentiation, if it is functional or non-functional, and if the tumor tests positive for somatostatin receptors. Read more about grade and degree of differentiation.

Somatostatin analogs, like octreotide or lanreotide, chemotherapy, targeted therapy, and PRRT are often used to treat stage IV GI tract NETs. These treatments may be used alone or in combination. If a person has carcinoid syndrome, somatostatin analogs are usually the primary treatment for many people with a well-differentiated, grade 1 or grade 2 metastatic NET. If somatostatin analogs do not stop the tumor growth, then PRRT or everolimus may be recommended. For people with well-differentiated, grade 3 disease, the treatment plan may include somatostatin analogs, chemotherapy, and/or PRRT.

Surgery is sometimes used to relieve symptoms rather than eliminate the cancer. If distant metastases are not causing symptoms, then surgery may not be needed. Radiation therapy may also be offered to help relieve symptoms from stage IV GI tract NETs, such as cancer that has spread to the bone.

Participation in clinical trials is encouraged. Palliative and supportive care will also be important to help relieve symptoms and side effects.

For many people, a diagnosis of metastatic cancer is very stressful and difficult. You and your family are encouraged to talk about how you feel with doctors, nurses, social workers, or other members of your health care team. It may also be helpful to talk with other patients, such as through a support group or other peer support program.

The information in this section is based in part on the ASCO guideline, “Systemic Therapy for Tumor Control in Metastatic Well-differentiated Gastroenteropancreatic Neuroendocrine Tumors.” Please note that this link will take you to a different ASCO website.

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Remission and the chance of recurrence

A remission is when a tumor cannot be detected in the body and there are no symptoms. This may also be called having “no evidence of disease” or NED.

A remission may be temporary or permanent. This uncertainty causes many people to worry that the NET will come back. While many remissions are permanent, it is important to talk with your doctor about the possibility of the cancer returning. Understanding your risk of recurrence and the treatment options may help you feel more prepared if the NET does return. Learn more about coping with the fear of recurrence.

If the NET returns after the original treatment, it is called a recurrent NET. It may come back in the same place (called a local recurrence), nearby (regional recurrence), or in another place (distant recurrence).

If a recurrence happens, a new cycle of testing will begin to learn as much as possible about it. After this testing is done, you and your doctor will talk about the treatment options. Often the treatment plan will include the treatments described above, such as surgery, chemotherapy, and radiation therapy, but they may be used in a different combination or given at a different pace. Your doctor may suggest clinical trials that are studying new ways to treat recurrent GI tract NETs. Whichever treatment plan you choose, palliative and supportive care will be important for relieving symptoms and side effects.

People with a recurrent tumor sometimes experience emotions such as disbelief or fear. You are encouraged to talk with your health care team about these feelings and ask about support services to help you cope. Learn more about dealing with cancer recurrence.

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If treatment does not work

Recovery from a GI tract NET is not always possible. If the tumor cannot be cured or controlled, the disease may be called advanced or incurable.

This diagnosis is stressful, and for some people, an advanced NET is difficult to discuss. However, it is important to have open and honest conversations with your health care team to express your feelings, preferences, and concerns. The health care team has special skills, experience, and knowledge to support patients and their families and is there to help. Making sure a person is physically comfortable, free from pain, and emotionally supported is extremely important.

Planning for your future care and putting your wishes in writing is important, especially at this stage of disease. Then, your health care team and loved ones will know what you want, even if you are unable to make these decisions. Learn more about putting your health care wishes in writing.

People who have advanced disease and who are expected to live less than 6 months may want to consider hospice care. Hospice care is designed to provide the best possible quality of life for people who are near the end of life. You and your family are encouraged to talk with your doctor or a member of your palliative care team about hospice care options, which include hospice care at home, a special hospice center, or other health care locations. Nursing care and special equipment can make staying at home a workable option for many families. Learn more about advanced cancer care planning.

After the death of a loved one, many people need support to help them cope with the loss. Learn more about grief and loss.

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The next section in this guide is About Clinical Trials. It offers more information about research studies that are focused on finding better ways to care for people with a GI tract NET. Use the menu to choose a different section to read in this guide.