Small intestine neuroendocrine tumours are rare cancers that develop in specialized hormone-producing cells of the digestive system, often presenting with subtle symptoms that can mimic everyday ailments, making treatment planning both complex and highly personalized.

Understanding Treatment Goals for Small Intestine Neuroendocrine Tumours

When someone is diagnosed with a small intestine neuroendocrine tumour, often referred to as a small bowel NET, the treatment approach depends on many individual factors. The main goals of treatment include managing symptoms that affect daily life, slowing down how quickly the tumour grows, preventing complications, and improving overall quality of life. Because these tumours often grow slowly, treatment strategies can be quite different from those used for faster-growing cancers.^[1][10]

The stage of the disease plays a crucial role in deciding which treatment path to follow. Some patients are diagnosed when the tumour is still small and contained within the small bowel, while others may already have cancer that has spread to nearby lymph nodes or even to the liver. The tumour’s grade, which refers to how abnormal the cells look under a microscope and how quickly they are likely to grow, also influences treatment choices. Patient characteristics such as age, overall health, and whether the tumour is producing excess hormones all factor into the treatment plan.^[8][11]

Medical societies and specialist centres have established standard treatments that have been proven effective over years of clinical experience. At the same time, researchers continue to explore new therapies through clinical trials, offering patients access to innovative treatment options that may provide additional benefits. Understanding these treatment approaches helps patients and their families navigate the journey ahead with greater confidence.^[4]

Standard Treatment Approaches

Surgery as the Main Treatment

Surgery remains the cornerstone of treatment for small intestine neuroendocrine tumours. When the tumour has not spread beyond the bowel or nearby lymph nodes, removing it completely through an operation can potentially cure the disease. The type of surgery depends on where the tumour is located within the small intestine. The small bowel has three sections: the duodenum (which connects to the stomach), the jejunum (the middle part), and the ileum (the lower part that connects to the large bowel).^[3][11]

During surgery, the surgeon typically removes the section of small intestine containing the tumour along with nearby lymph nodes. This type of operation is called a resection. The surgery can be performed through traditional open surgery, where a larger incision is made in the abdomen, or through keyhole (laparoscopic) surgery, where several small incisions are made instead. The choice between these approaches depends on the size and location of the tumour, as well as whether it has spread to surrounding tissues.^[11][2]

Small intestine NETs often spread to the mesentery, which is the double fold of tissue that anchors the intestine in the abdomen and contains blood vessels and lymph nodes. When tumours spread to this area, they can cause significant scarring and fibrosis. This scarring can trap loops of intestine, leading to bowel obstruction, or encase blood vessels, causing problems with blood flow. Surgeons must carefully remove these mesenteric tumours and address the fibrosis to prevent future complications.^[2][13]

In some patients, the cancer has already spread to the liver by the time of diagnosis. Even in these cases, surgery may still play an important role. Removing as much tumour as possible, a process called debulking, can help reduce symptoms and make other treatments more effective. Some patients may also benefit from liver-directed therapies that specifically target tumours in the liver.^[10][16]

Somatostatin Analogues for Symptom Control

Many small intestine NETs produce hormones that enter the bloodstream and cause symptoms. One of the most common hormone-related conditions is carcinoid syndrome, which causes facial flushing (sudden redness and warmth of the face), chronic watery diarrhoea, and sometimes wheezing. These symptoms occur because the tumour releases substances like serotonin and other hormones into the blood. Carcinoid syndrome typically develops when the cancer has spread to the liver, though it can occasionally occur earlier.^[1][2]

Somatostatin analogues are medications that mimic a natural hormone in the body called somatostatin. These drugs work by blocking the release of hormones from the tumour cells, which helps control symptoms of carcinoid syndrome. The two main somatostatin analogues used are octreotide and lanreotide. They are given as injections, typically once a month, and can significantly improve quality of life by reducing flushing and diarrhoea.^[2][13]

Beyond controlling symptoms, somatostatin analogues also appear to slow tumour growth. Clinical studies have shown that these medications can extend the time before the disease progresses, making them a valuable part of long-term management. Patients often continue these treatments for months or even years. Side effects are generally mild and may include temporary digestive upset, abdominal discomfort, or changes in blood sugar levels. Most people tolerate these medications well with few interruptions to daily activities.^[10]

Chemotherapy and Targeted Therapies

For some patients, particularly those with more aggressive tumours or widespread disease, chemotherapy may be recommended. Chemotherapy involves using drugs that kill rapidly dividing cancer cells. Traditional chemotherapy drugs used for NETs include combinations such as streptozocin with fluorouracil or capecitabine with temozolomide. These medications work by interfering with the cancer cells’ ability to grow and divide.^[11]

Chemotherapy is typically reserved for tumours that are growing faster or not responding to other treatments. It is given in cycles, with periods of treatment followed by rest periods to allow the body to recover. Side effects can include fatigue, nausea, reduced blood cell counts, and increased risk of infection. Healthcare teams monitor patients closely during chemotherapy and provide supportive medications to manage side effects.^[11]

Targeted cancer drugs represent a newer approach that focuses on specific molecular pathways involved in tumour growth. One example is everolimus, which belongs to a class of drugs called mTOR inhibitors. These medications work by blocking signals that tell cancer cells to grow and divide. Another targeted drug sometimes used is sunitinib. Targeted therapies often have different side effects compared to traditional chemotherapy, such as mouth sores, skin problems, or effects on blood pressure and blood sugar.^[11]

Liver-Directed Treatments

When small intestine NETs spread to the liver, specialized treatments can be used to target tumours in that organ specifically. These approaches include hepatic artery embolization, where blood flow to the tumour is blocked, causing cancer cells to die from lack of nutrients and oxygen. In some cases, chemotherapy drugs or radioactive particles are combined with embolization to increase effectiveness.^[11][16]

Another liver-directed approach is radiofrequency ablation, which uses heat to destroy tumour tissue. These procedures are typically performed by interventional radiologists and can be done without major surgery. They are particularly useful for patients who cannot undergo liver resection or when tumours are not responding well to systemic medications.^[16]

Innovative Treatments in Clinical Trials

Peptide Receptor Radionuclide Therapy (PRRT)

One of the most promising advances in treating small intestine neuroendocrine tumours is peptide receptor radionuclide therapy, commonly known as PRRT. This innovative treatment combines a targeting molecule with a radioactive particle. The targeting molecule binds to specific receptors on the surface of NET cells, delivering radiation directly to the tumour while sparing most healthy tissue.^[11][14]

The most commonly used PRRT drug is lutetium Lu 177 dotatate. It works because many NETs have high levels of somatostatin receptors on their cell surfaces. The drug locks onto these receptors like a key fitting into a lock, then releases radiation that damages the cancer cells’ DNA, causing them to die. PRRT is given through an intravenous infusion, typically in a series of four treatments spaced about eight weeks apart.^[14]

Clinical trials have shown that PRRT can significantly slow disease progression and improve symptoms in patients with advanced small intestine NETs. In major studies, patients receiving PRRT experienced longer periods before their disease worsened compared to those receiving standard doses of somatostatin analogues alone. Many patients also reported improvements in their quality of life, with better control of symptoms like diarrhoea and flushing.^[10]

Side effects of PRRT are generally manageable. Some patients experience temporary nausea during or shortly after the infusion, and there can be effects on blood cell production or kidney function, which requires monitoring through regular blood tests. Because this therapy involves radioactive material, patients receive it in specialized nuclear medicine facilities with appropriate safety measures. PRRT has become increasingly available at major cancer centres in Europe, the United States, and Australia.^[14][16]

Immunotherapy Research

Immunotherapy represents an exciting frontier in cancer treatment that helps the body’s own immune system recognize and attack cancer cells. While immunotherapy has shown remarkable success in treating some types of cancer, research is still ongoing to determine how best to use these approaches for neuroendocrine tumours. Clinical trials are exploring various immunotherapy strategies, including checkpoint inhibitors that release the brakes on immune cells, allowing them to fight cancer more effectively.^[11]

Small intestine NETs have certain characteristics that make immunotherapy research particularly interesting. Scientists are studying the genetic and molecular features of these tumours to identify which patients might benefit most from immune-based treatments. Some trials are combining immunotherapy with other treatments to see if this increases effectiveness.^[10]

Novel Molecular Targeted Agents

Researchers continue to discover new molecular pathways that drive NET growth, leading to development of novel targeted therapies. These experimental drugs are being tested in Phase I, Phase II, and Phase III clinical trials. Phase I trials focus primarily on safety, determining the correct dose and identifying potential side effects in small groups of patients. Phase II trials examine whether the treatment shows promise in fighting the cancer, enrolling more patients and measuring response rates. Phase III trials compare the new treatment against current standard treatments in large patient groups to determine if it offers meaningful benefits.^[4][12]

Some experimental approaches under investigation include drugs that target specific growth factor receptors, medications that interfere with blood vessel formation in tumours (anti-angiogenic agents), and agents that block multiple signalling pathways simultaneously. Researchers are also exploring whether certain drug combinations might be more effective than single agents alone.^[10]

Clinical trials for small intestine NETs are being conducted at specialized centres worldwide, including locations in the United States, Europe, and Australia. Patients interested in participating in clinical trials should discuss this option with their healthcare team. Trials often have specific eligibility criteria based on factors like disease stage, previous treatments received, and overall health status. Participation in a clinical trial may provide access to cutting-edge treatments before they become widely available, while also contributing to medical knowledge that helps future patients.^[3][10]

Biomarker Research and Personalized Medicine

An important area of current research involves identifying biomarkers, which are measurable indicators that can predict how a tumour will behave or how it might respond to specific treatments. Scientists are studying genetic mutations, protein expression patterns, and other molecular features of small intestine NETs. This research aims to enable more personalized treatment decisions, where therapy is tailored to the unique characteristics of each patient’s tumour rather than using a one-size-fits-all approach.^[8]

Blood tests measuring substances called chromogranin A and specific breakdown products of serotonin (5-HIAA) are already used to monitor disease activity. Researchers are working to develop more sophisticated blood-based tests that could detect disease progression earlier or predict which treatments will be most effective. Advanced imaging techniques that can better visualize tumours and their metabolic activity are also under development.^[8][10]

Most common treatment methods

• Surgery
  • Surgical resection of the primary tumour in the small intestine along with nearby lymph nodes is the main curative treatment when disease is localized
  • Can be performed through open surgery with a large abdominal incision or through keyhole (laparoscopic) surgery using several small incisions
  • Removal of mesenteric tumours and associated fibrosis to prevent bowel obstruction and vascular complications
  • Debulking surgery to remove as much tumour as possible, even when cure is not achievable, to reduce symptoms and improve response to other treatments
  • Liver resection or other surgical approaches when tumours have spread to the liver
• Somatostatin Analogues
  • Monthly injections of octreotide or lanreotide to control symptoms of carcinoid syndrome including flushing and diarrhoea
  • Block hormone release from tumour cells by mimicking natural somatostatin
  • Also slow tumour growth and extend time before disease progression
  • Generally well-tolerated with mild side effects such as digestive upset or blood sugar changes
  • Used for long-term management, often continued for months to years
• Peptide Receptor Radionuclide Therapy (PRRT)
  • Lutetium Lu 177 dotatate combines a targeting molecule that binds to somatostatin receptors on NET cells with a radioactive particle
  • Delivers radiation directly to tumour cells while sparing healthy tissue
  • Typically given as four intravenous infusions spaced eight weeks apart
  • Clinical trials show significant slowing of disease progression and symptom improvement
  • Available at specialized nuclear medicine centres in the United States, Europe, and Australia
• Chemotherapy
  • Drug combinations such as streptozocin with fluorouracil or capecitabine with temozolomide
  • Reserved for more aggressive tumours or widespread disease not responding to other treatments
  • Works by interfering with cancer cells’ ability to grow and divide
  • Given in cycles with treatment periods followed by rest periods for recovery
  • Side effects include fatigue, nausea, reduced blood counts, and increased infection risk
• Targeted Cancer Drugs
  • Everolimus (mTOR inhibitor) blocks signals that promote tumour growth
  • Sunitinib and other agents that target specific molecular pathways
  • Different side effect profile compared to traditional chemotherapy
  • May include mouth sores, skin problems, blood pressure changes, or blood sugar effects
• Liver-Directed Therapies
  • Hepatic artery embolization blocks blood flow to liver tumours, causing cancer cells to die
  • Chemoembolization combines embolization with chemotherapy drugs
  • Radioembolization uses radioactive particles along with embolization
  • Radiofrequency ablation uses heat to destroy tumour tissue
  • Performed by interventional radiologists without need for major surgery
• Immunotherapy (Clinical Trials)
  • Checkpoint inhibitors that enhance the immune system’s ability to fight cancer
  • Still under investigation in clinical trials to determine effectiveness for NETs
  • Being studied alone and in combination with other treatments
  • Research focuses on identifying which patients might benefit most