Large Bowel Neuroendocrine Cancer

Understanding colorectal neuroendocrine cancer

The colorectal region includes the colon, caecum and rectum, which forms most of the large bowel. It helps absorb water, store waste, and move stool out of the body.

The appendix is anatomically connected to the caecum but is usually discussed separately because appendiceal neuroendocrine cancers have distinct features.

Colorectal neuroendocrine cancers begin in neuroendocrine cells within the bowel lining. They are different from the more common bowel cancer called adenocarcinoma.

The behaviour of the cancer depends on several factors, including:

• Where the tumour is located
• Whether it is well differentiated or poorly differentiated
• The tumour grade
• The Ki-67 index
• Whether lymph nodes are involved
• Whether the cancer has spread to the liver or other organs

Colorectal neuroendocrine cancers are often grouped into neuroendocrine tumours (NETs), neuroendocrine carcinomas (NECs), or mixed neuroendocrine and non‐neuroendocrine neoplasms (MiNEN)

Types of colorectal neuroendocrine cancer

Neuroendocrine tumours (NETs)

Neuroendocrine tumours are usually well differentiated by definition. This means the cancer cells still look somewhat like normal neuroendocrine cells under the microscope.

Some NETs grow slowly, but they can still spread or become difficult to treat if diagnosed late.

NETs are graded based on how quickly the tumour cells are dividing. This is usually measured using the Ki-67 index and mitotic count.

Neuroendocrine carcinomas (NECs)

Neuroendocrine carcinomas are poorly differentiated and high grade. They grow more quickly and are often more aggressive than well-differentiated NETs.

NECs are more likely to spread early, including to the liver, lymph nodes, lungs, or other organs.

Treatment for NECs is usually different from treatment for slower-growing NETs and may involve chemotherapy.

Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs)

Some cancers contain both neuroendocrine cancer cells and non-neuroendocrine cancer cells, usually adenocarcinoma cells.

These are called mixed neuroendocrine-non-neuroendocrine neoplasms, or MiNENs.

MiNENs can behave aggressively and often need treatment planning by a multidisciplinary team.

Rectal and Colonic NETs

Rectal NETs deserve a specific mention because they can behave differently from NETs in the colon. They are among the more commonly found colorectal NETs, and are often discovered incidentally during colonoscopy, and are frequently small and low-grade.

When small, low grade, and detected at an early stage, they often have an excellent outlook and may be treated with endoscopic removal.

Colon NETs, particularly those arising in the right colon or caecum, are often diagnosed at a later stage and may require more complex treatment.

Symptoms of colorectal neuroendocrine cancer

Colorectal neuroendocrine cancers may not cause symptoms in the early stages. Some are found during colonoscopy or imaging for another reason.

When symptoms occur, they may include:

• Abdominal pain or cramping
• Bloating
• Diarrhoea
• Constipation
• Changes in bowel habits
• Rectal bleeding
• Blood in the stool
• Unexplained weight loss
• Fatigue
• Bowel obstruction
• Anaemia

Symptoms can overlap with many other bowel conditions. Persistent or unexplained bowel changes should always be assessed by a healthcare professional.

Hormone-related symptoms

Some well-differentiated colorectal NETs produce hormones. If these hormones enter the bloodstream, they can cause a group of symptoms called carcinoid syndrome.

This is more likely when a functional NET has spread to the liver, because hormones may bypass normal breakdown processes.

Symptoms may include:

• Facial flushing
• Watery diarrhoea
• Wheezing
• Fast heartbeat
• Low blood pressure episodes
• Abdominal cramping

Not everyone with a colorectal NET develops carcinoid syndrome. It is less common than mechanical bowel symptoms, but it is important to recognise.

Diagnosis of colorectal neuroendocrine cancer

Diagnosis usually involves a combination of endoscopy, biopsy, pathology testing, imaging, and blood or urine tests.

1. Colonoscopy and biopsy

A colonoscopy allows doctors to examine the inside of the large bowel using a flexible camera.

If a tumour or abnormal area is found, a biopsy can be taken. The tissue sample is then examined by a pathologist to confirm the diagnosis.

2. Pathology and grading

Pathology is essential because it helps determine whether the cancer is a NET, NEC, or MiNEN.

The tumour may be tested for neuroendocrine markers such as:

• Chromogranin A
• Synaptophysin

The pathologist will also assess the Ki-67 index and mitotic count, which help determine tumour grade.

3. Imaging scans

Imaging helps show the size of the tumour and whether it has spread.

Tests may include:

• CT scan
• MRI
• Ga-68 DOTATATE PET/CT scan
• FDG PET/CT scan in selected higher-grade cancers

Octreotide scans, also called somatostatin receptor scintigraphy, have now been largely replaced by Ga-68 DOTATATE PET/CT in Australia, but may occasionally be used in specific situations.

The most appropriate scan depends on the tumour type, grade, and clinical situation.

4. Blood and urine tests

Blood and urine tests may be used to check for neuroendocrine tumour markers or evidence of hormone activity.

These may include:

• Chromogranin A
• 5-HIAA urine or blood testing
• Other tests based on symptoms and specialist advice

These tests are not used alone to diagnose colorectal neuroendocrine cancer, but they may help with monitoring in selected cases.

Grading and staging

Grading and staging help guide treatment.

Grade describes how quickly the tumour cells are growing. It is usually based on the Ki-67 index, mitotic count and whether the tumour cells are well differentiated or poorly differentiated. .

Stage describes how far the cancer has spread. It considers whether the cancer is confined to the bowel, involves nearby lymph nodes, or has spread to distant organs such as the liver.

A low-grade, localised NET is usually treated differently from a high-grade NEC or metastatic disease.

Treatment options for colorectal neuroendocrine cancer

Treatment depends on tumour type, grade, stage, symptoms, and overall health.

A multidisciplinary team may include a gastroenterologist, colorectal surgeon, medical oncologist, radiation oncologist, nuclear medicine specialist, radiologist, pathologist, dietitian, and NET nurse.

Surgery

Surgery is often the main treatment for localised colorectal neuroendocrine cancer, although very small low-risk rectal NETs may sometimes be treated with local or endoscopic removal.

This may involve removing the section of bowel that contains the tumour, along with nearby lymph nodes.

Surgery may be used to:

• Remove localised disease
• Prevent or treat bowel obstruction
• Manage bleeding
• Reduce tumour burden in selected cases

The type of surgery depends on the tumour’s location, size, spread, and whether it is a NET, NEC, or MiNEN.

Somatostatin analogues

Somatostatin analogues, such as octreotide or lanreotide, may be used for some well-differentiated NETs.

They can help:

• Control hormone-related symptoms
• Reduce flushing or diarrhoea
• Slow tumour growth in selected cases

They are more commonly used when the tumour has somatostatin receptors.

Chemotherapy

Chemotherapy is more commonly used for high-grade NECs, MiNENs, or rapidly growing disease.

It may also be considered when cancer has spread and is not suitable for surgery alone.

The chemotherapy approach depends on tumour biology and specialist recommendation.

PRRT

Peptide receptor radionuclide therapy (PRRT) may be considered for selected advanced NETs that have somatostatin receptors on the surface of the tumour cells.

PRRT delivers targeted radiation to cancer cells. It is usually considered when disease is advanced, progressing, and suitable for functional imaging.

Targeted therapies

Targeted therapies may be considered in selected advanced well-differentiated NETs. These treatments aim to interfere with specific pathways that help cancer cells grow.

Their use depends on tumour type, previous treatments, receptor status, and specialist advice.

Liver-directed therapies

If colorectal NETs spread predominately to the liver, liver-directed treatment may be considered in some cases.

Options may include:

• Embolisation
• Chemoembolisation
• Selective internal radiation therapy (SIRT)
• Radiofrequency ablation
• Surgery in selected cases

These treatments aim to control liver disease, reduce symptoms, or slow progression.

Complications of colorectal neuroendocrine cancer

Colorectal neuroendocrine cancers can cause complications depending on tumour size, location, and spread.

Possible complications include:

• Bowel obstruction
• Bleeding
• Anaemia
• Weight loss
• Liver metastases
• Carcinoid syndrome
• Carcinoid crisis in rare situations
• Carcinoid heart disease in people with prolonged hormone exposure

Carcinoid crisis is a rare but serious hormone surge that can occur during surgery, anaesthesia, or significant stress. People with functional NETs should have careful perioperative planning.

Nutrition and bowel function

Treatment for colorectal neuroendocrine cancer can affect digestion and bowel habits.

Some people experience diarrhoea, constipation, urgency, bloating, or changes in how often they pass stool.

Nutrition support may be helpful after bowel surgery or during treatment.

Support may include:

• Managing diarrhoea or constipation
• Maintaining weight
• Preventing dehydration
• Addressing vitamin or mineral deficiencies
• Managing bile acid malabsorption if relevant
• Adjusting diet after bowel surgery

An oncology dietitian can help tailor advice to the person’s treatment and symptoms.

Living with colorectal neuroendocrine cancer

Living with colorectal neuroendocrine cancer can involve physical symptoms, treatment side effects, uncertainty, and regular monitoring.

People may need support with:

• Understanding their pathology report
• Managing bowel symptoms
• Preparing for surgery or chemotherapy
• Coping with fatigue
• Managing hormone-related symptoms
• Navigating scans and follow-up
• Emotional and practical support

Because these cancers are rare, it is important that people feel informed and supported when making treatment decisions.

Follow-up and surveillance

Follow-up depends on the tumour type, grade, stage, and treatment received.

A follow-up plan may include:

• Physical review
• Colonoscopy where appropriate
• CT or MRI scans
• Functional imaging in selected cases
• Blood or urine markers
• Monitoring bowel function
• Checking for recurrence or progression

Higher-grade cancers, NECs, MiNENs and metastatic disease usually require closer monitoring.

Research and future directions

Research is improving how colorectal neuroendocrine cancers are diagnosed and treated.

Important areas include:

• Better use of Ki-67 and molecular profiling
• Improved imaging with Ga-68 DOTATATE PET/CT and FDG PET/CT
• More personalised treatment for NETs, NECs, and MiNENs
• New systemic therapies for advanced disease
• Better prediction of recurrence risk
• Improved management of liver metastases

Clinical trials may be available for some people with advanced or treatment-resistant disease.

Support available through NeuroEndocrine Cancer Australia

Colorectal neuroendocrine cancer is rare and can be difficult to understand, especially when different terms such as NET, NEC, MiNEN, grade, stage, and carcinoid syndrome are used.

NeuroEndocrine Cancer Australia provides support for people affected by neuroendocrine cancer, including:

• Access to the NET nurse, dietitian and counselling services
• Patient and carer resources
• Education about diagnosis and treatment
• Support for navigating specialist care
• Information about symptoms and follow-up
• Connection to relevant support pathways

If you or someone you care for has been diagnosed with large bowel neuroendocrine cancer, support is available.