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Neuroendocrine tumours (NETs)

What are NETs? 

The neuroendocrine system is a network of glands and nerve cells that make hormones and release them into the bloodstream. These hormones help control normal body functions, for example digesting food.

Neuroendocrine cells are found throughout the body, but mainly in the gastro-intestinal tract (including large and small bowel), pancreas and lungs.

NETs are an uncommon type of tumour that forms in these cells. The type is generally defined by where the abnormal cells come from and can range from low grade (slow growing) to high grade (fast growing). NETs that produce extra amounts of hormones can cause certain symptoms and are referred to as functional tumours. However, not all NETs produce extra hormones (non-functional).

Types and related symptoms

Most NETs develop slowly over several years but they can also be aggressive and grow quickly, spreading to other parts of the body and causing problems. In the early stages NETs may not cause symptoms. If you do have symptoms, it will depend on where in the body the tumour is and if the tumour cells are producing hormones. You may experience general symptoms such as fatigue and loss of appetite.

Gastro-intestinal

These start in the large bowel and small bowel. Types of gastro-intestinal NETs include:

  • gastric NETs, in the stomach
  • duodenal NETs, in the duodenum (the first section of the small bowel)
  • small bowel NETs, including the jejunum and ileum
  • large bowel NETs, in the colon
  • appendiceal NETs, in the appendix
  • rectal NETs, near the anus.

If functional, these NETs may release high levels of hormones such as serotonin, which can be associated with symptoms of diarrhoea, facial flushing and tiredness.

Other symptoms may include abdominal pain and bloating, changes in bowel or bladder habits including bowel obstruction or bleeding from the anus, and asthma-like wheezing.

Pancreatic

Pancreatic NETs begin in the endocrine cells of the pancreas and make up approximately 7% of the more common pancreatic (adenocarcinoma) cancer diagnoses. About 90% of pancreatic NETs do not produce extra hormones.

Functional pancreatic NETs are very rare and most are named after the hormone they overproduce:

  • insulinomas, produce too much insulin (causing low blood sugar levels)
  • glucagonomas, produce too much glucagon (causing high blood sugar levels)
  • gastrinomas, produce too much gastrin (causing stomach ulcers)
  • somatostatinomas, produce too much somatostatin (causing abdominal discomfort and weight loss)
  • VIPomas, produce too much vasoactive intestinal peptide (causing severe watery diarrhoea).

Functional NETs produce extra amounts of hormones, and the first symptoms will often be related to this excess hormone production. Other symptoms may include:

  • low blood sugar levels (hypoglycaemia) causing shaking, sweating, confusion, dizziness and rapid heartbeat
  • high blood sugar levels (hyperglycaemia) which may cause increased urination, excessive thirst and blurred vision
  • indigestion (heartburn) and stomach ulcers
  • rash in the groin area
  • unexplained weight loss
  • nausea or vomiting
  • changes in bowel habits, including diarrhoea or pale, foul-smelling stools that are hard to flush away.

Non-functional NETs do not produce extra hormones and rarely cause symptoms in the early stages. Symptoms often appear only once the cancer is large enough to affect nearby organs, or has spread (most commonly to the liver). As the tumour grows it may also cause pain in the upper abdomen, side or back.

Lung

The four types of NETs that develop in the lung include:

  • typical carcinoid
  • atypical carcinoid
  • large cell neuroendocrine carcinoma
  • small cell lung neuroendocrine cancer.

Symptoms may include repeated pneumonia or chest infections, coughing up blood, shortness of breath, wheezing and chest pain.

Other NETs

Merkel cell carcinoma – also known as neuroendocrine carcinoma of the skin, this is a rare cancer involving the Merkel cells in the top layer of the skin. Merkel cell carcinoma grows quickly and often returns and spreads. More information is available from the Australasian Merkel Cell Carcinoma Interest Group (AMIGOs) and the Australian Cancer Research Foundation.

Merkel cell carcinoma usually occurs as a painless hard nodule (tumour) in the skin that grows rapidly and is often red, purple or blue, or can be flesh-coloured. Some patients feel the nodule is under (rather than in) the skin. The most common location is skin that has been exposed heavily to the sun such as the face, head and neck.

Neuroblastoma – this tumour typically starts in the adrenal glands (above the kidneys), but can also be found near the spinal cord. It affects immature or developing nerve cells in children. More information is available from Neuroblastoma Australia. 

Symptoms may include:

  • painless lump or swelling in the tummy, chest or neck
  • swollen legs, arms, upper chest, neck and face
  • loss of appetite or feeling full
  • weight loss
  • changes in bowel or bladder habits
  • difficulty breathing or swallowing
  • headaches or dizziness
  • drooping eyelid 
  • trouble feeling or moving arms and legs. 

More information on all the different types of NETs, including others such as thymic, testicular, prostate, ovarian and endometrial, multiple endocrine neoplasia, pheochromocytoma, paraganglioma and medullary thyroid carcinoma, is available from NeuroEndocrine Cancer Australia

 

How common are NETs? 

NETs are not common but the number of people being diagnosed is slowly increasing. There is an almost equal risk for males and females. Around 3700 Australians are diagnosed with a NET each year, with most new cases being diagnosed in people aged 40 years or over.

Australia has the highest number of Merkel cell carcinoma cases in the world, with older men most at risk. Neuroblastoma is more likely in children under the age of 5 years.

Learn more about rare cancer

Risk factors

The causes of most NETs are not known. However, there are several risk factors:

  • Genetic factors – some rare, inherited diseases can put people more at risk of NETs. These include multiple endocrine neoplasia (MEN 1, MEN 2), Von Hippel-Lindau (VHL) syndrome, tuberous sclerosis complex and neurofibromatosis.
  • Pre-existing conditions – some NETs may be linked to pre-existing conditions such as peptic ulcers (in the stomach or duodenum) and diabetes.
  • Sun exposure – Merkel cell carcinoma is linked to overexposure to the sun and ultraviolet light. It may also be caused by the Merkel cell polyomavirus (MCV).

Carcinoid syndrome 

When NET tumours produce excess hormones, it can cause a group of symptoms known as carcinoid syndrome. Some of these symptoms include facial flushing, diarrhoea, wheezing and carcinoid heart disease leading to shortness of breath.

It is most common in people with gastro-intestinal NETs, including duodenal and small bowel, and lung NETs that have spread (metastasised) in the body. However, not all people with these NETs will develop the syndrome.  

Diagnosis

NETs can be difficult to find and are sometimes diagnosed when patients are undergoing tests for a different condition. Many doctors may not have seen or treated Merkel cell carcinoma before, so diagnosis is often delayed.

If your doctor thinks that you may have a NET (or one of the syndromes associated with NETs) they will take your medical history, perform a physical examination and carry out certain tests.

Further tests

If the results suggest that you may have a NET, your doctor will refer you to a specialist who will carry out further tests such as: 

  • Blood tests – including a full blood count.
  • Urine tests – to measure serotonin production (which can be produced by NETs).
  • Endoscopy – a flexible tube with a camera on the end (endoscope) is inserted under sedation down the throat into the stomach, or into the anus and large bowel to view your gut.
  • Bronchoscopy – a thin, tube-like instrument with a light and a lens for viewing (bronchoscope) is inserted through the nose or mouth to view your lungs. The bronchoscope is also able to remove tissue to obtain a diagnosis.
  • CT or MRI scans – special painless machines are used to scan and create pictures of the inside of your body. Before the scan you may have an injection of dye into one of your veins, which makes the pictures clearer.
  • PET scan – you will be injected with a small dose of radioactive glucose (sugar) solution to help cancer cells show up brighter on the scan.
  • Biopsy – removal of some tissue from the affected area for examination under a microscope.
  • Echocardiogram – a painless ultrasound to examine your heart valves, which can sometimes be affected. 

For a directory of specialists in NET care and treatment, contact NeuroEndocrine Cancer Australia. For a directory of specialists in Merkel cell carcinoma care and treatment, contact Australasian Merkel Cell Carcinoma Interest Group (AMIGOs)

 

Nutrition and exercise

If you have been diagnosed with a NET, both the cancer and treatment will place extra demands on your body. Eating well and being active can help you cope with some of the common side effects of cancer treatment, speed up recovery and improve your quality of life.

Some people with NETs, especially pancreatic NETs or those who have had bowel surgery, may need specific dietary advice. The symptoms of carcinoid syndrome may be triggered by certain foods and drinks, and some vitamin deficiency syndromes may be more common.

You can discuss individual nutrition and exercise plans with health professionals such as dietitians, exercise physiologists and physiotherapists.

Treatment

You will be cared for by a multi-disciplinary team (MDT) of health professionals during your treatment for NETs. These may include a gastroenterologist, endocrinologist, lung physician and physiotherapist, among others. For neuroblastoma, the team will include childhood cancer specialists, including a paediatric oncologist.

Discussion with your doctor will help you decide on the best treatment for your tumour depending on:

  • the type of NET you have, including if it is functional (hormone producing) and the symptoms you have
  • where it is in your body
  • the grade of the tumour, if known
  • whether or not the NET has spread (stage of disease)
  • your age, fitness and general health
  • your preferences.

Treatments can be given alone, in combination or one after the other. This is called multi-modality treatment. If the NET is slow-growing and not causing any symptoms you may not need immediate treatment. 

Complementary therapies are designed to be used alongside conventional medical treatments and can increase your sense of control, decrease stress and anxiety, and improve your mood.

Surgery

Surgery is the main treatment for most types of NETs, especially for people with early-stage disease who are in otherwise good health. Surgery usually involves removing the cancer and some surrounding healthy tissue to ensure the tumour is completely removed.

The type of operation depends on the size of the tumour and where it is located.


Surgery for early-stage non-functional pancreatic NETs

As with more common types of pancreatic cancer, surgeries include:

  • Whipple procedure – treats tumours in the head of the pancreas and removes the pancreas, the first part of the small bowel, the gall bladder and bile duct. Also called pancreaticoduodenectomy.
  • Distal pancreatectomy – removes tumours in the tail or body of the pancreas and often also removes the spleen.
  • Total pancreatectomy – removes the entire pancreas and spleen. This may be the best option if the cancer is large, or in multiple places in the pancreas.

Surgery for advanced non-functional pancreatic NETs

Surgery can be used to treat blockages caused by the tumour and to reduce the size of the tumour.

  • Stenting – if the tumour has blocked the common bile duct or duodenum, a small tube called a stent can be inserted.
  • Debulking – if the whole tumour can’t be removed, the surgeon may try to remove some of it. This surgery, called debulking, is not always possible and will depend on the tumour’s position and size.

For Merkel cell carcinoma the surgery may also involve removing the lymph nodes close to the tumour.

Surgery for early-stage NETs is often given with the aim of cure, although there can also be benefits from removing areas of tumour, even if the cancer has spread (e.g. to reduce the risk of bowel obstruction in small bowel NETs). However, there are risks and potential complications involved in surgery. It is important to have your surgery in a specialist centre with surgical and anaesthetic experience with NETs.

Common side effects for surgery include bleeding, damage to nearby tissue and organs (including nerves), drug reactions, pain, infections, blood clots, weak muscles and lymphoedema.

Somatostatin analogues (SSAs) 

The body produces a hormone called somatostatin, which controls how organs release several other hormones. SSAs are medicines that are similar to somatostatin. SSAs can slow down or prevent tumour growth, as well as slow down the release of hormones from NETs. They may be used to help control symptoms associated with carcinoid syndrome such as facial flushing and diarrhoea.

The main SSAs used in Australia are octreotide LAR and lanreotide. These are generally given as monthly injections, but may be given more often if required.

Common side effects include loss of appetite, nausea, vomiting, bloating, bowel issues such as constipation or diarrhoea, abdominal pain, gallstones and fatigue.

Theranostics – peptide receptor radionuclide therapy (PRRT)

PRRT, a form of radiation treatment, may be offered to some people with NETs. It involves using a radioactive compound bound together with a small molecule that attaches strongly to NET cells. This allows high doses of radiation to be delivered to specific sites of tumours wherever they have spread throughout the body. 

The most common form of PRRT is 177Lu-Dota-octreotate (LuTate) therapy. PRRT is available only in certain specialised treatment centres in each state (generally in metropolitan areas).

You may have a dose of chemotherapy in tablet form before PRRT as a combined treatment. PRRT is injected into your vein via a cannula, with a session lasting around four hours. Most people have four sessions about 8–12 weeks apart. Re-treatment with PRRT is possible in selected cases.

Common side effects include nausea, vomiting, fatigue, short-term hair loss, loss of fertility, kidney damage and blood disorders.

Chemotherapy

Chemotherapy is the use of drugs to kill or slow the growth of cancer cells. You may have one chemotherapy drug, or a combination of drugs, either through a drip or as a tablet. This is because different drugs can destroy or shrink cancer cells in different ways.

Chemotherapy is commonly given in treatment cycles which may be daily, weekly or monthly. Your treatment will depend on the grade and type of tumour you have, and the drugs being given. Chemotherapy is more often given to treat high-grade NETs.

Common side effects include fatigue, loss of appetite, nausea, bowel issues such as constipation or diarrhoea, hair loss, mouth sores, skin and nail problems, increased chance of infections and loss of fertility.

Targeted therapy

Targeted therapy uses drugs that work in a different way to chemotherapy drugs. While chemotherapy drugs affect all rapidly dividing cells and kill cancer cells, targeted therapy drugs attack specific molecules within cells and work by blocking cell growth.

People with advanced pancreatic NETs may be offered targeted therapies such as sunitinib (Sutent) and everolimus (Afinitor) to slow the growth of the tumour. Everolimus may also be used to treat advanced gastro-intestinal, pancreatic and lung NETs. These drugs are in capsules that you swallow.

External beam radiation therapy 

Radiation therapy uses high energy rays to destroy cancer cells, where the radiation comes from a machine outside the body. NETs may be treated with external beam radiation therapy in selected cases, depending on the location of tumours and your symptoms. It may be used: 

  • if the cancer can’t be removed with surgery
  • if the cancer has spread to other parts of the body
  • after surgery, to destroy any remaining cancer cells and stop the cancer coming back (such as for Merkel cell carcinoma).

Radiation therapy can shrink the cancer down to a smaller size, which may help relieve symptoms such as pain. Sometimes chemotherapy is given as well as radiation therapy, for example to treat lung NETs.

Radiation therapy does not hurt and is usually given in small doses over a period of time to minimise side effects, which commonly include fatigue, loss of appetite, nausea, bowel issues such as diarrhoea, abdominal cramps and excess wind, bladder issues, hair loss, dry mouth, skin problems, lymphoedema and loss of fertility.

Treatment for liver tumours

NETs, particularly gastro-intestinal and pancreatic, often spread to the liver. The tumours in the liver are called metastases. Treatments to control these liver lesions may include:

Radiofrequency ablation (RFA) and microwave ablation – Using an ultrasound or CT scan, a needle is inserted through the abdomen into the liver tumour. The needle sends out radio waves or microwaves that produce heat and destroy the cancer cells.

Transarterial chemoembolisation (TACE) – A catheter is inserted into the hepatic artery, which supplies blood to the liver. A chemotherapy drug together with tiny particles (called microspheres) is released into the artery, which blocks the flow of blood into the tumour. This may cause the tumour to shrink.

Selective internal radiation therapy (SIRT) – Also known as radioembolisation, the radiologist inserts a catheter into the liver’s main artery and then delivers tiny radioactive beads (SIR-spheres) to the liver through the catheter. The beads give a direct dose of radiation to the tumour.

PRRT can also be used to treat liver lesions in selected cases.

Question checklist

Asking your doctor questions will help you make an informed choice. You may want to include some of the questions below in your list.

  • What type of NET do I have? Where is it located?
  • How far has it spread? What stage of cancer do I have?
  • What grade is my tumour/tumours?
  • Have you treated this type of cancer before?
  • What are the treatment options for me? What do you recommend and why?
  • What is the goal of treatment for my type of NET?
  • What are the possible risks and side effects of my treatment? How will these be managed?
  • What impact will treatment have on my fertility?
  • How long will treatment take?
  • Is this treatment covered by Medicare/private insurance? Will there be extra expenses?
  • If the cancer comes back, how will I know?
  • What are the possible benefits and risks to joining a clinical trial? What is being tested and why? How many people will be involved in this trial?
  • If I cannot get onto a clinical trial, can I still pay for a drug that is currently in trial?

 

Life after treatment

For some people a low-grade NET can be successfully removed with surgery, and there is a good chance it won’t come back after treatment. However, regular check-ups including physical examinations and further imaging scans will be needed over a long period.

Unfortunately, NETs are difficult to treat and they can come back after treatment. If the cancer does come back, treatment will depend on where the cancer has returned to in your body and your symptoms. For Merkel cell carcinoma, major breakthroughs recently in understanding the cancer and how to treat it make long-term survival possible.

In many cases of advanced NETs, treatment will focus on controlling the tumour, managing any symptoms such as pain and improving your quality of life without trying to cure the disease. This is called palliative treatment. Palliative care can be provided in the home, in a hospital, in a palliative care unit or hospice, or in a residential aged care facility. 

Learn more

 

Understanding Neuroendocrine Tumours (NETs)

Download our Understanding NETs fact sheet to learn more

Download now

 

Additional support:

Your doctor or nurse may suggest you take part in a clinical trial. Doctors run clinical trials to test new or modified treatments and ways of diagnosing disease to see if they are better than current methods. Find out more: Australian Cancer TrialsNeuroEndocrine Cancer Australia, Australasian Gastro-Intestinal Trials Group (AGITG), Neuroblastoma Australia and Melanoma and Skin Cancer (MASC) Trials. 

Further support and information can be accessed from Cancer Council (13 11 20), Rare Cancers Australia (1800 257 600), Australasian Merkel Cell Carcinoma Interest Group (AMIGOs) and Melanoma Institute Australia

Expert content reviewers:

Dr David Chan, Medical Oncologist, Royal North Shore Hospital, NSW; Leslye Dunn, Consumer; Prof Gerald Fogarty, Radiation Oncologist, St Vincent’s Hospital, NSW; Katie Golden, Consumer; Dr Grace Kong, Nuclear Medicine Physician, Peter MacCallum Cancer Centre, VIC; Caitriona Nienaber, 13 11 20 Consultant, Cancer Council WA; Elizabeth Paton, Melanoma and Skin Cancer Trials Group, NSW.

Page last updated:

The information on this webpage was adapted from Understanding Neuroendocrine Tumours (NETs) - A guide for people affected by cancer (2021 edition). This webpage was last updated in August 2021.

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