Neuroendocrine cancer

Dr Daleen Geldenhuys clarifies why neuroendocrine cancer is difficult to recognise, diagnose and treat.

Neuroendocrine cells are distributed widely throughout the body. These cells serve as the communicator cells between surrounding cells and the brain.

Neuroendocrine tumours can therefore arise in most organs; known by the nickname: Nearly Everywhere Tumours (NETs). While features of these tumours are unique to the site of origin, other characteristics are shared regardless of site. 

The classification of NETs is independent of origin. The growth rate of the tumour and the extent of local spread determine the treatment that the patient will receive.

Classification

Low-grade: Growth rate of < 2%

Intermediate: Growth rate of 2-20%

High-grade: NET >20%, NEC > 20% (neuroendocrine carcinoma), Mixed neuroendocrine and non-neuroendocrine neoplasm (MiNEN)

The classification is important and completely different to other tumours. Although we differentiate between a neuroendocrine neoplasm/tumour (NET) and a neuroendocrine carcinoma (NEC), both variations can metastasise to other organs. 

Each individual patient with a neuroendocrine neoplasm, regardless of the growth rate of the tumour is so unique that clinical trials are exceedingly difficult to conduct.

NET/Cs can present in several different ways

• As a result of hormone production by the tumour. Chronic flushing and/or diarrhoea are the typical manifestations of carcinoid syndrome, which is the result of secretion of serotonin and other substances into the circulation. Patients may develop hypertension, anxiety and even constipation.
• As a result of tumour growth. Small bowel NETs may cause chronic/recurrent abdominal pain, occasionally leading to bowel obstruction. Metastatic tumours in the liver can cause right upper quadrant pain and an enlarged liver.
• Some are found incidentally. Many NETs are discovered during endoscopic or radiographic procedures planned for other purposes; this is especially true of NETs of the stomach and rectum.

How to diagnose

1. Imaging such as CT scan, MRI, octreoscan or gallium Ga-68 dotatate PET scan.

2. Blood test: Chromogranin, if a specific tumour is suspected such as a gastric tumour producing gastrin, that can also be tested. It shouldn’t be used as a screening test and can be falsely elevated. 

3. Urine test: Excretion of by-product of serotonin metabolism: 5-HIAA: 24-hour urine collection.

4. Endoscopy: Upper and lower endoscopy (with attention to the terminal ileum) should be performed for the evaluation of metastatic NET if an unknown primary site can’t be established through imaging studies. 

Treatment

It differs vastly for every patient, but the options include:

1. Surgery, for diagnosis, treatment, and relief of symptoms. Occasionally metastasectomy is an option if the tumours can be seen and are limited.
2. Chemotherapy for high-grade neuroendocrine cancers but also certain low-grade neuroendocrine tumours.
3. Sandostatin analogues which are monthly slow-releasing injections. This controls hormone secretion and acts as an antiproliferative agent.
4. Radioactive therapy which differs from normal radiation as the isotope binds the somatostatin receptors and may also kill the tumour cells. This is highly-specialised therapy and is considered under certain circumstances.
5. Watch and wait may be an approach if the patient is well and has no symptoms of active disease.

What makes NETs so different?

Patients are diagnosed late in the course of the disease because of non-specific symptoms. On average, the tumour has been present for more than three years before it’s found. 

Even though grade 1 and 2 NETs are slow-growing, they can also metastasise. It’s often difficult to see metastases as the tumours may not be well-circumscribed and can be a diffuse infiltrate, like grinding pepper over your pasta. You may not see it on scans, but you may very well suffer from hormone secretion by these scattered cells. This is a difficult concept for people to understand and may make it more difficult for the patient as it’s not understood by the public and not by most healthcare professionals. This is a difficult tumour to recognise, diagnose and treat. It’s especially important that your symptoms are taken seriously especially if present for a long time.