Neuroendocrine Tumours (NETs): Comprehensive Cancer Information

Neuroendocrine Tumours (NETs): A Comprehensive Guide

General Information

Unlike many cancers that are identified by their location, Neuroendocrine Tumours (NETs) are classified based on their cell of origin. These tumours develop from neuroendocrine cells, which are found throughout the body, meaning a NET can potentially form anywhere.

NETs are considered rare, with many new diagnoses reported each year in India. In the past, these tumours were sometimes classified as benign (non-cancerous) or malignant (cancerous). Today, however, all NETs are viewed as potentially cancerous because they are all believed to have the capacity to spread, or metastasise, although this spread can be either slow or quick, depending on the specific tumour.

Despite some NETs being aggressive, they are generally considered highly treatable. Most patients who are diagnosed before the cancer has spread have an excellent five-year survival rate of over 95%.

What are Neuroendocrine Cells?

Neuroendocrine cells serve as a bridge between the nervous system and the endocrine (hormone) system. They receive signals from the nervous system and, in response, produce hormones that help regulate vital bodily functions, including breathing, digestion, and heart rate. A NET begins when one of these neuroendocrine cells mutates and starts multiplying rapidly, forming a tumour.

How NETs are Classified:

NETs can be categorised in a couple of ways that are important for diagnosis and treatment:

Functional or Non-Functional

Neuroendocrine cells naturally produce hormones, and so can the tumours they form.

  • Functional NETs produce and release hormones, which often leads to specific symptoms and may require different treatment approaches.
  • Non-Functional NETs do not produce hormones.

Location

While NETs can grow anywhere, the most common sites include the gastrointestinal tract, the lungs, and the pancreas. The primary location of the NET is a critical factor in determining a patient's treatment plan and long-term outlook (prognosis).

Carcinoid Tumours

Many slow-growing NETs were once referred to as "carcinoid tumours" (meaning cancer-like). Today, this term is used for only a very narrow subset of cancers. Almost all growths that would have been called carcinoid tumours in the past are now simply classified and referred to as NETs.

Risk Factors for NETs

A risk factor is anything that increases a person's chance of developing cancer. Risk factors for NETs include:

Hereditary Cancer Syndromes

This includes conditions such as von Hippel Lindau disease.

Other Inherited Conditions

Such as multiple endocrine neoplasia and neurofibromatosis type 1.

Age

NETs are very rare in children.

Symptoms

Since neuroendocrine tumours can form anywhere in the body, the symptoms will vary widely depending on the tumour's location.

General Symptoms

NETs may cause symptoms that are common to many types of cancer, including:

  • Fatigue
  • A new, growing lump or mass
  • Unexplained weight loss

Location-Specific Symptoms

Gastrointestinal NETs

Symptoms are similar to other cancers in the digestive tract and may include:

  • Rectal bleeding or blood in the stool
  • A change in the size, shape, or colour of the stool
  • Discomfort or the urge to have a bowel movement when there is no actual need
  • Bloating or a feeling of fullness
  • Pain in the abdomen or lower back

Lung NETs

Symptoms typically align with general lung cancer symptoms.

Pancreatic NETs

The signs are similar to those of other pancreatic cancers.

Symptoms of Functional NETs

Functional NETs release hormones, which can cause physical symptoms and changes in behaviour. In addition to any location-related symptoms, a functional NET may cause:

  • Persistent flushing of the face
  • Persistent, often severe diarrhoea
  • Severe gastric ulcers
  • High or low blood sugar
  • Changes in bathroom habits, including frequent urination
  • Dizziness or shakiness
  • Anxiety or confusion

Diagnosis

Early and accurate diagnosis is vital for a successful outcome in treating neuroendocrine tumours.

If your doctor suspects a NET, they will perform a physical examination and ask detailed questions about your health, lifestyle, and family medical history. The tests ordered will depend on the location of the suspected tumour and are used to diagnose, monitor, or assess the patient's symptoms.

Common Diagnostic Tests for NETs

Imaging Exams

The exact imaging test will depend on the possible tumour location, but common exams include CT scans, MRI scans, X-rays, and ultrasounds.

If a gastrointestinal NET is suspected, an endoscopy may be ordered. This procedure involves inserting a thin plastic tube with a camera into the rectum or mouth to look for signs of cancer.

Biopsy

This is the only definitive way to diagnose a NET. It involves retrieving suspected cancer cells for study under a microscope.

Blood and Urine Tests

These tests cannot definitively diagnose a NET but are used to monitor hormone levels, which helps doctors understand and assess the patient's symptoms, particularly with functional tumours.

NET Grading and Staging

The prognosis and treatment plan are significantly influenced by how the disease is graded and staged:

Stage

Describes the size of the tumour and how far it has spread (metastasised) from its original site.

Grade

Describes how abnormal the cancer cells look when examined under a microscope. Cells that appear more abnormal are given a higher grade, and these cancers are generally more aggressive.

Treatment

Given that neuroendocrine tumours are rare, it is especially important to find a care team with experience in treating them. At SSCHRC, we have specialist physicians who focus on these tumours, allowing them to design informed and comprehensive treatment plans. Many of our doctors also conduct research into NETs, working to develop new treatments. As a result, SSCHRC often has a large number of clinical trials available for NET patients, offering new therapies that may not be available elsewhere.

NET Treatment Plans

Regardless of the tumour's location, the preferred treatment for most NETs is surgery to remove the entire tumour. This approach can be curative for patients whose disease has not yet metastasised, and in some cases, surgery that removes the primary tumour and all metastases can also be an effective cure.

If it is not possible to remove the entire tumour (e.g., due to a hard-to-reach location or widespread metastases), doctors may still perform surgery to remove a part of the tumour to help relieve related symptoms. If the patient's tumours cannot be entirely removed, a complete cure may not be possible, and the disease is then managed through treatments designed to slow or stop its progression.

Treatment plans for a NET are highly individualised and depend on many factors, including the tumour's location, whether it is functional or non-functional, and the advancement of the disease.

Common NET Treatments

Active Surveillance

For slow-growing NETs, doctors may recommend active surveillance. This involves the patient undergoing regular tests (blood, urine, and imaging exams) to monitor for tumour growth. Treatment is only initiated if and when the disease progresses. This can be a suitable approach for older patients who may find surgery or other therapies difficult.

Surgery

Many NETs can be removed surgically, particularly if diagnosed before they have spread beyond the main tumour and nearby lymph nodes. The specific surgical options depend on the tumour's location, and the procedures are similar to those for other types of tumours at that site.

Chemotherapy

Chemotherapy drugs work by killing fast-growing cells, including cancer cells.

Targeted Therapy

Also known as precision medicine, targeted therapy is different from traditional chemotherapy. It works at a cellular level by interfering with specific molecules (proteins) that cancer cells need to survive, multiply, and spread, thus halting or slowing the growth or spread of the cancer.

Radiation Therapy

This uses focused beams of energy to destroy cancer cells.

Peptide Radionuclide Therapy

This is a method of delivering cancer-killing radiation directly to the tumour. A radioactive chemical is combined with another chemical that attaches specifically to cancer cells. The patient receives this combined liquid through an intravenous (IV) infusion.

Somatostatin Analogs

These drugs are used to slow tumour growth and help relieve cancer symptoms. While initially used only for functional NETs (hormone-producing), recent studies show they can also be effective for non-functional NETs.

Liver-Directed Therapies

When NETs metastasise, they often spread to the liver. Liver-directed therapies use a catheter sent through an artery to deliver treatments directly to the metastasis. These treatments include chemotherapy, the use of radioactive beads to kill cancer cells, or using the catheter to heat and kill the blood vessels that feed the tumour.

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