Dr Azura Deniel, Consulting Oncologist at the Ampang Puteri Specialist Hospital, Kuala Lumpur tells us more about a slow-growing type of cancer known as neuroendocrine tumours or NETs. 

What are neuroendocrine tumours (NETs) and who are most affected?

NETs are a rare type of cancer or tumour that develops from cells that release hormones into the bloodstream called neuroendocrine cells. As hormone-releasing neuroendocrine cells are widely distributed throughout the body, NETs can occur almost anywhere in the body.

NETs usually occur in younger patients in their 30s and 40s and often affect the pancreas, lungs, and small intestine.

How common are NETs?

Dr A: Although NETs are rare, data seems to indicate there is a slight increase in incidence of the disease over the past decade. In Singapore, the incidence of NETs rose from 1.4% in 1993, to 3.3% in 2003 and 7.9% in 2014.

Meanwhile, a 10-year analysis in Malaysia found that almost 50% of NET patients presented with an advanced stage of the disease, in which the cancer had spread to distant anatomical sites.

What are the signs and symptoms of NETs?

Symptoms depend on where the tumour is in the body and what hormones it produces. When NETs occur in the lung, the patient suffers from wheezing or persistent coughs, while NETs of the digestive system or gastrointestinal NET (GI-NET), cause patients to experience prolonged diarrhoea, constipation, or progressive abdominal pain. Tumours that arise from the proximal colon, which is the first part of the large intestine and the small intestine, cause a host of symptoms referred to as carcinoid syndrome.

Carcinoid syndrome presents with chronic flushing, diarrhoea, cramps, wheezing, low blood pressure, and heart problems. This occurs when the tumour releases abnormally excessive amounts of hormones into the bloodstream, such as serotonin.

Other symptoms of NETs include unexplained weight loss, rectal bleeding, and insomnia, while some symptoms may mimic conditions such as irritable bowel syndrome (IBS) or peptic ulcer disease.

Unfortunately, most NETs do not cause any symptoms at all and by the time the symptoms do appear, the cancer has become quite advanced.

Why are NETs often detected or diagnosed late?
Symptoms can often mimic or overlap with other non-cancerous diseases. For example, like NETs, Irritable Bowel Syndrome (IBS) may also cause chronic diarrhoea and abdominal pain, so when patients, particularly younger patients, present with intestinal problems General Practitioners (GPs) often associate it with IBS.

In younger female patients who present with abdominal pain, it is possible to misdiagnose the symptoms as endometriosis, while in older females, it is possible to link hot flushes and mood changes to pre-menopausal symptoms.

Due to the risk of NETs being misdiagnosed, it is crucial to be proactive and see a doctor for further investigation or follow-ups when symptoms do not respond to prescribed treatment or medication and continue to persist. Further tests will then be needed to determine the actual cause of the symptoms.

How are NETs diagnosed?

The initial tests for diagnosing NETs include blood and urine investigations. The blood test may check for abnormal levels of certain proteins such as the level of chromogranin A (CgA), which may be elevated in NETs.

A urine test may check for a 24-hour urinary excretion of 5-hydroxyindoleacetic acid (5HIAA), the end product of serotonin metabolism, and has a high sensitivity and specificity for carcinoid syndrome. Some patients may require an endoscopic or colonoscopy examination, which is then followed up with an imaging investigation to look for tumours, including an ultrasound, X-ray, CT scans, an MRI, and a more specific imaging test called octreotide or dotatate scan.

The dotatate scan is performed by injecting a mildly radioactive liquid (octreotide) through the veins, which travels through the bloodstream and attaches to the tumour, while a camera-equipped device visually highlights cancer cells. NETs are confirmed with a biopsy.

How quickly can NETs progress? Are NETs staged the same way as other cancers?
Dr A:
The good news is that unlike other cancers, NETs are often slow-growing, and staged differently from solid tumour cancers such as liver cancer. NETs are graded as 1,2, or 3 based on their location, grade, and how different the cells appear under the miscroscope. Grade 1 tumours are low-grade with cells that divide and grow slowly, grade 2 is intermediate and grade 3 consists of high-grade fast-growing tumours and rapidly dividing cells.

Generally, the lower the tumour grade and degree of differentiation the better it is for the patient, and with the right treatment and care, patients can often live well for many years.

How are NETs treated?
The treatment for NETs depends on where the tumour is located, the tumour’s stage, and the overall health of the patient. Surgery is the first go-to treatment to halt progression of the disease, but the majority of patients are diagnosed after the tumour has spread (metastasised) to other parts of the body, especially the liver, and this is when other treatment modalities are recommended.

When the cancer has spread, a medication called somatostatin analogues (SSA), such as octreotide or lanreotide may be prescribed. This medicine stops the body from producing excessive hormones, and thus reduces the severity of symptoms and delaying tumour progression. SSAs have been shown to improve the clinical outcome of NETs, including delaying disease progression and improving survival rates.

Other available treatment options are peptide receptor radioligand therapy (PRRT), which delivers targeted radiation to NET cells, trans-arterial chemoembolisation, chemotherapy, and targeted therapy.

Ultimately, the earlier NETs are detected and treatments introduced, the better the survival rates for the patient. If you experience symptoms like diarrhoea, abdominal pains, hot flushes, insomnia, wheezing, abnormally low blood pressure, unexplained weight loss, and rectal bleeding which do not seem to respond to the treatment prescribed by your general practitioner (GP), it’s important to consult a specialist.