Neuroendocrine Cancer

Neuroendocrine tumors (also called NETs or NENs) of the gastrointestinal tract form in neuroendocrine cells distributed along the GI tract and pancreas. While these tumors can develop anywhere in the GI tract, the most common primary tumor sites are the small intestine (30.8%), rectum (26.3%), colon (17.6%), pancreas (12.1%), and appendix (5.7%). Many NETs are slow-growing and discovered incidentally, often detected through endoscopic ultrasound, CT, and MRI.

The reported worldwide incidence of GI NETs is 8.2 per 100,000 people. Incidence has risen worldwide, with a more than 6-fold increase in the United States between 1973 and 2012, with GI NETs showing the highest increases of any NET site. Rates are rising steadily in North America, Asia, and Europe, and overall survival for patients with GI NETs appears to be improving over time. NENs now constitute one of the fastest-growing categories of GI cancers. Overall survival for patients with GI NETs appears to be improving with time.

What is neuroendocrine cancer?

There are thousands of neuroendocrine cells in your body, and many of them line the organs of the GI tract and release hormones into your digestive system. These cells turn messages from the brain into signals that tell other organs in the body what to do. Cancer can form inside of these cells. While these cancers can form in many places throughout the body, many neuroendocrine cancers begin in the GI organs.

NET tumors in the stomach, small intestine, colon, rectum, and appendix are referred to as GI NET.

NET tumors in the pancreas are referred to as pNET or PanNET.

For many patients, a diagnosis can be delayed up to seven years. Many are misdiagnosed with IBS or other conditions for years before the correct diagnosis.

Carcinoid syndrome

NETs can cause carcinoid syndrome. Liver metastases can release serotonin directly into the bloodstream, bypassing breakdown in the liver. This can cause a patient to experience severe diarrhea, GI cramping, a flushed face and neck, wheezing, rapid heartbeat, and carcinoid heart disease. Sometimes the symptoms of carcinoid syndrome are what lead to a discovery of NET.

Staging NET cancer

Neuroendocrine tumors need to be graded and staged. The grade can determine whether the cancer is well-differentiated or poorly differentiated. This is determined by how the cells look under a microscope. The WHO classification for NET is nuanced and will take these factors into consideration: 

Well-differentiated 

Well-differentiated cancer cells look like normal, healthy cells, and they tend to be less aggressive and slower growing. For well-differentiated cancers found in GI organs, for example the pancreas or appendix, there is a unique staging system based on the organ it was found. These staging systems will range from stage 1-4, with 4 being the most aggressive and spread to other parts of the body. These cancers are also referred to as carcinoids in the GI tract or pancreatic neuroendocrine tumors (pNETs) in the pancreas. Well-differentiated NET are defined as neuroendocrine tumor (NET G1, G2, G3).

Poorly differentiated 

Poorly differentiated cancer cells look abnormal, and they tend to be more aggressive and quicker growing. For these cancers, staging will be based on the 0-4 staging system typically used for other cancer types in that organ. These cancers are also called neuroendocrine carcinomas (NECs). Poorly differentiated NET are defined as neuroendocrine carcinoma (NEC, G3).

What causes neuroendocrine cancer?

Risk factors put you at a higher risk of getting cancer. Some risk factors can be controlled with lifestyle changes, and others cannot. Older age, smoking, and obesity increase your risk of many cancers.

Just because you have a risk factor, that doesn’t mean you will get cancer. 

These are scenarios researchers have found that can increase your risk of getting a NET cancer.

• Hereditary syndromes like multiple endocrine neoplasia type 1 (MEN1) or type 4 (MEN4), neurofibromatosis type 1 (NF1), tuberous sclerosis complex (TSC1 or TSC2), or Von Hippel-Lindau (VHL) syndrome. 
• Certain conditions like atrophic gastritis, pernicious anemia, or Zollinger-Ellison syndrome.

Preventing NET cancers

It is difficult to prevent neuroendocrine cancer, because researchers are still learning about what causes this rare cancer to form. However, patients are encouraged to follow healthy lifestyle actions to prevent cancer in general. For those at high risk, talk to a doctor about tests to stay on top of so you can detect any cancers at its earliest stages. 

Learn more about cancer prevention from the American Institute for Cancer Research.

What are some neuroendocrine cancer statistics? 

According to a study published in Endocrine Oncology:

• The annual global incidence of neuroendocrine neoplasms is estimated at 5.86 per 100,000 people per year, and continues to increase.
• The median age at diagnosis globally is 60 years, though NET in the appendix typically affects younger patients (often under 40).
• Overall NEN tends to occur in males more than females globally, but there are significant variations influenced by genetic, hormonal, and environmental factors.

A Springer Nature Link article explained Global differences:

• North America: small intestinal and rectal NETs are most prevalent
• Asia, rectal and pancreatic NETs predominate
• Europe, small intestinal and pancreatic NETs are most common

What are my odds of surviving it?

Five-year overall survival rates  rectal NETs have the best prognosis at 88.5%, followed by appendiceal (81.3%), small intestinal (68.1%), gastric (64.1%), colon (54.6%), and pancreatic NETs (37.6%).

What types of tests should I expect to undergo?

Neuroendocrine cancer is challenging to find, and it often has few symptoms. 

Doctors may use these tests to find and diagnose NET:

• Physical exam
• Blood tests (chromogranin A)
• Urine tests (24-hour urine 5-HIAA)
• MIBG scan
• Imaging (Gallium-68 DOTATATE PET/CT, ultrasound, MRI)
• Endoscopy (upper and lower)
• Biopsy
  

Ask your doctor about these additional tests—ideally before you begin treatment.

• Biomarker testing
• Genetic testing

I’m facing a diagnosis: What are my next steps?

If you’re facing a neuroendocrine cancer diagnosis, the GI Cancers Alliance is here for you. 

If you’re newly diagnosed, you ideally need treatment at a center with dedicated NET expertise and a multidisciplinary tumor board.

The grade of your NET will come into play. Cancer grades are based on a scale of 1-3, and it helps identify how slow or fast-growing the cancer is. This will help your doctors choose a treatment plan for your unique situation. 

Whether the tumor is “functional” or "non-functional" will also play a role in treatment. Functional tumors secrete hormones. 

Treatment plans may include:

• Somatostatin analogues
• Peptide receptor radionuclide therapy (PRRT) with with Lutathera
• Surgery 
• Radiation
• Chemotherapy 
• Immunotherapy
• Targeted therapy
• Medicines to control hormones

We strongly encourage you to get a second opinion from another trusted doctor so you can feel confident moving forward.