How are carcinoid tumours treated?

Carcinoid tumours are rare types of tumours that are slow growing. They may arise from multiple sites within the body, affecting the neuroendocrine cells.

Neuroendocrine cells act like nerve cells to receive and transfer signals from the nervous system by releasing hormones. These cells are found in all organs throughout the body.

Therefore, carcinoid tumours fall under the category of neuroendocrine tumours and may occur in the lungs, stomach, small intestine, colon, rectum, pancreas, liver, and appendix.

The symptoms of carcinoid tumours vary according to the location of the tumour in the body. Some carcinoid tumours may not show any signs and symptoms and could be discovered only during routine medical examinations.

Signs and symptoms based on types of carcinoid tumours

The most common areas of carcinoid tumours are the lungs and the digestive system. The signs and symptoms include:

Carcinoid tumours in lungs

• Breathing difficulties

• Chest pain

• Wheezing

• Coughing up blood

Carcinoid tumours in the digestive system

• Nausea and vomiting

• Abdominal pain

• Diarrhea

• Weight loss

• Bowel obstruction

• Rectal pain bleeding

What is carcinoid syndrome?

Carcinoid syndrome is characterized by a group of symptoms that occur due to the release of certain chemicals into the bloodstream.

This syndrome is typically observed in advanced stage carcinoid tumours and presents with symptoms such as skin flushing (redness and warmth in the face), diarrhea, decrease in blood pressure, weakness, dehydration, rapid heartbeat, purplish rashes and cardiovascular complications in later stages.

Diagnostic methods for carcinoid tumours

Various laboratory tests and imaging scans are ordered in patients presenting with any symptoms of carcinoid tumours. These include:

• Imaging

Diagnostic scans including Computed Tomography (CT) scans, various types of Positron Emission Tomography (PET) scans and radionuclide scans are ordered to determine the location and size of the tumour in the body.

• Biopsy

A small tissue sample is taken from the tumour site for microscopic examination of the tumour cells. The tissue sample may be collected with a needle or through a small surgical procedure. The type of biopsy is decided based on the location of the tumour.

• Endoscopy

Endoscopy involves passage of a long, thin, tube into a body cavity/tube, which has a small camera to examine various areas in the body. Various types of endoscopies including upper gastrointestinal tract endoscopy,  bronchoscopy and colonoscopy are used to detect and biopsy carcinoid tumours.

• Urine test

Urine analysis is carried out to determine the excess levels of chemicals and hormones produced by carcinoid tumours. Excess serotonin released by carcinoid tumours is metabolized to 5-hydroxy-indole-acetic acid (5-HIAA), a diagnostic marker for these tumours. A 24-hour urine sample has 73% sensitivity and 100% specificity for diagnosing carcinoid tumours

• Blood tests

Serum analysis is done through blood samples to determine the levels of Chromogranin A (CgA), a protein that is secreted by neuroendocrine cells. Elevated CgA levels are found in 85% to 100% of patients with carcinoid tumours, irrespective of whether the tumour is actively releasing hormones or not.

Treatment methods for carcinoid tumours

Treatment for carcinoid tumours may vary for each individual depending on a number of factors. These include:

• the primary location of the tumour,

• the extent to which the tumour has spread,

• secretion of hormones by the tumour,

• overall health condition

• preferences.

Moreover, treatment usually involves a multidisciplinary approach, which uses a combination of treatments.

 Below are the different treatment methods for carcinoid tumours:

• Surgery

Surgical resection is the preferred initial treatment method, for localized tumours and even in some cases where it has spread to other structures, especially as

Surgery involves complete removal of the tumour in cases of early detection. However, complete removal may not be possible in advanced stage carcinoid tumours and debulking surgery is opted in these situations.

Debulking surgery involves removal of the tumour to the maximum extent to control the signs and symptoms.

• Medications

Medications are prescribed to block hormone secretion by the tumours in order to control the signs and symptoms caused by hormone oversecretion.

There are mainly two medications – Octreotide and Lanreotide, which are known as somatostatin analogues.

Somatostatin analogues slow down the production of hormones and inhibit most of the gastrointestinal and endocrine hormones.

These are given as subcutaneous injections (beneath the skin) once in every four weeks and help to control symptoms such as flushing and diarrhea. These medications may have some common side effects such as nausea, abdominal pain and bloating.

• Chemotherapy

Chemotherapy involves use of strong cytotoxic drugs which help kill tumour cells in advanced carcinoid tumours. These drugs inhibit hormone and protein synthesis along with stimulation of the immune system. Molecularly targeted drugs also are used in carcinoid tumours.

It is usually used as second-line or subsequent treatment for patients who develop disease even after surgery and/or recur despite having adequate surgery and other drugs or are not operable.

• Peptide Receptor Radionuclide Therapy (PRRT)

It is a molecular targeted therapy in which a cell targeting protein is combined with radioactive material.

The drug is injected into the bloodstream where the protein binds to the tumour cells and delivers high dose radiation to directly kill the tumour cells.

• Management of liver metastasis

The liver is one of the most common sites of metastasis in carcinoid tumours and  liver-limited metastatic disease has a relatively good prognosis.

Management of liver metastasis is an important aspect in the treatment of carcinoid tumours as it can help prolong survival. It includes surgical approaches such as liver resection, debulking surgery, radiofrequency ablation (heat), cryoablation (cold), laser therapy, ablative radiation or a combination of these along with medical therapy to kill tumour cells in the liver.

Future targeted therapies

Several new drugs and targeted therapies are being developed for the treatment of carcinoid tumours. It is well known that cellular signaling pathways are the main factors involved in the growth, differentiation and hormone expression of carcinoid tumours.

Numerous other pathways and targeted molecules are currently under investigation. Recent studies have demonstrated the importance of alternative pathways such as targeting the Vascular Endothelial Growth Factor (VEGF) and mammalian Target of Rapamycin (mTOR).

These have shown promising results in patients diagnosed with advanced staged carcinoid tumours, given the unique nature of these tumours.