Rectal Neuroendocrine Cancer

Overview

Rectal neuroendocrine cancer, also called a rectal neuroendocrine neoplasm (rNEN), is a type of cancer that starts in the specialised neuroendocrine cells lining the rectum. These cells help regulate hormone release and nerve signalling in the lower digestive tract.

Rectal neuroendocrine cancers were previously known as rectal carcinoid tumours. Today they are classified on a spectrum from slow-growing, well-differentiated neuroendocrine tumours (NETs) to fast-growing, poorly differentiated neuroendocrine carcinomas (NECs), each requiring a different approach to treatment.

One of the most important features of rectal neuroendocrine cancer is that the majority of tumours are found when they are small and low-grade, often discovered by accident during a routine colonoscopy. Small rectal NETs that are found early and treated promptly have an excellent outlook. Larger or high-grade tumours carry a greater risk of spreading and require a more intensive treatment approach.

Because rectal neuroendocrine cancer behaves quite differently from the more common rectal adenocarcinoma, and differently from neuroendocrine cancers arising elsewhere in the bowel, specialist assessment and management are essential.

At NeuroEndocrine Cancer Australia (NECA), our mission is to support patients and families affected by neuroendocrine cancers, including rectal neuroendocrine cancer. We offer resources, educational materials, and advocacy to improve understanding and care. For support after a rectal neuroendocrine cancer diagnosis, contact our NET Nurse, Counsellor and Dietitian services.

Understanding rectal neuroendocrine cancer

The rectum is the final section of the large bowel, connecting the colon to the anus. Its inner lining contains specialised neuroendocrine (enteroendocrine) cells that help coordinate bowel function and hormone responses.

Rectal neuroendocrine cancers have a distinctive biology that sets them apart from neuroendocrine cancers elsewhere in the gastrointestinal tract. Importantly, they rarely produce serotonin, which means they rarely cause the classic carcinoid syndrome seen with midgut tumours such as small bowel NETs. Instead, some rectal neuroendocrine tumours may produce other substances such as glucagon-like peptides or pancreatic polypeptides, which do not typically cause significant systemic symptoms.

Most rectal neuroendocrine cancers are small at the time of diagnosis, often under 10 mm, and are low-grade. These small tumours have a very low risk of spreading and are often successfully treated with endoscopic removal alone. Larger tumours, particularly those greater than 20 mm, carry a substantially higher risk of spread to lymph nodes or distant organs and require a more comprehensive treatment approach.

Rectal neuroendocrine cancers are among the most commonly diagnosed gastrointestinal neuroendocrine cancers, and their detection rates have increased significantly as colonoscopy screening has become more widespread.

Causes of rectal neuroendocrine cancer

The exact cause of rectal neuroendocrine cancer is not fully understood. Most cases occur sporadically, without a clear inherited cause or identifiable risk factor.

A small number of rectal neuroendocrine cancers are associated with inherited genetic syndromes, including Multiple Endocrine Neoplasia type 1 (MEN1), Neurofibromatosis type 1 (NF1), Von Hippel-Lindau (VHL) disease, and Tuberous Sclerosis Complex. Where an inherited syndrome is suspected, genetic counselling is recommended for the affected person and their family.

Some studies have identified an association between rectal neuroendocrine cancers and metabolic syndrome, including conditions such as raised triglyceride levels, low HDL cholesterol, and high blood pressure, though the precise nature of this relationship is not yet fully established.

Rectal neuroendocrine cancer occurs more frequently with increasing age and is more common in men, though it can develop in people of any age or sex.

Effects of rectal neuroendocrine cancer on the body

The way rectal neuroendocrine cancer affects the body depends primarily on the size and grade of the tumour and whether it has spread.

Small, well-differentiated rectal NETs often cause no significant effects on the body and may be found before they produce any symptoms at all.

Larger tumours can cause local effects in the rectum and pelvis, including pressure on surrounding structures, changes to bowel function, and rectal bleeding. In some cases, ongoing tumour related bleeding may contribute to iron-deficiency anaemia over time.

If the cancer spreads to the liver or other organs, systemic effects become more likely, though even in this setting rectal neuroendocrine cancers are unlikely to cause carcinoid syndrome because they do not typically secrete serotonin. This is an important distinction for people with rectal neuroendocrine cancer who may have read information about carcinoid syndrome in the context of other neuroendocrine cancer types.

Symptoms of rectal neuroendocrine cancer

Many rectal neuroendocrine cancers cause no symptoms at all and are discovered during a colonoscopy performed for another reason, such as routine bowel cancer screening or investigation of unrelated symptoms. This is particularly common for small, low-grade tumours.

When symptoms do occur, they usually relate to the local effects of the tumour in the rectum and may resemble more common conditions affecting the anus and rectum, such as haemorrhoids. This can sometimes delay diagnosis.

Symptoms may include:

• Rectal bleeding or blood noticed in the stool
• A change in bowel habits such as persistent loose stools or constipation
• Rectal or anal pain or discomfort
• A persistent feeling of incomplete bowel emptying
• Mucus discharge from the rectum
• Unexplained weight loss or fatigue in more advanced disease

Systemic hormone symptoms such as skin flushing, wheezing, or watery diarrhoea are rarely associated with rectal neuroendocrine cancers and should not be expected in the way they might be with other neuroendocrine cancer types. When these symptoms do occur in the context of rectal neuroendocrine cancer, it is unusual and warrants specialist assessment.

Diagnosis of rectal neuroendocrine cancer

Accurately diagnosing and staging rectal neuroendocrine cancer is essential to choosing the right treatment. Because these tumours can resemble other rectal conditions on initial examination, specialist review and a combination of endoscopic, pathological, and imaging investigations are required.

1. Endoscopy and biopsy

A flexible sigmoidoscopy or colonoscopy is usually the first step, allowing the lining of the rectum and colon to be directly visualised. Rectal neuroendocrine cancers typically appear as smooth, rounded, polypoid lesions with normal overlying mucosa.

If a suspicious lesion is identified, a tissue biopsy or endoscopic removal is performed and examined by a pathologist to confirm the diagnosis, assess the tumour type, and determine tumour grade.

2. Tumour grading

Once biopsy or endoscopic removal is performed, the tumour is graded based on how the cells look under the microscope (differentiation) and how quickly they are dividing (proliferation rate), assessed using a cellular marker called the Ki-67 index.

The current grading classification is:

• Grade 1 Neuroendocrine Tumour (NET) : Well-differentiated, with a Ki-67 index below 3 per cent. Slow-growing with a very low risk of spread.
• Grade 2 Neuroendocrine Tumour (NET) : Well-differentiated, with a Ki-67 index between 3 and 20 per cent. Intermediate growth rate.
• Grade 3 Neuroendocrine Tumour (NET): Well-differentiated but rapidly dividing, with a Ki-67 index above 20 per cent.
• Grade 3 Neuroendocrine Carcinoma (NEC): Poorly differentiated, highly aggressive, and rapidly growing.

Tumour grade and size together are the most important factors in determining treatment approach and prognosis.

3. Endorectal ultrasound

Endorectal ultrasound (EUS) is a specialised imaging tool used inside the rectum to precisely measure the depth to which the tumour has grown into the rectal wall. It is particularly important for tumours in the intermediate size range of 10 to 20 mm, where the choice between endoscopic removal and surgical resection depends on the extent of wall invasion.

4. Advanced imaging

Pelvic MRI and contrast-enhanced CT scanning of the chest, abdomen, and pelvis are used to assess for local invasion into surrounding structures and for spread to lymph nodes or distant organs such as the liver. The need for imaging depends on tumour characteristics, including size, grade, depth of invasion, and other risk factors.

For well-differentiated tumours, Gallium-68 DOTATATE PET/CT is a specialised functional imaging scan that detects neuroendocrine tumour cells throughout the body by targeting somatostatin receptors on their surface.

5. Blood tests and tumour markers

Chromogranin A (CgA) is a blood marker that may be elevated in some people with neuroendocrine cancer and is used alongside imaging to help assess disease extent and monitor response to treatment.

Because rectal neuroendocrine cancers rarely produce serotonin, urinary 5-HIAA testing (routinely used for midgut neuroendocrine cancers with carcinoid syndrome) is not routinely recommended. However, it may be considered if symptoms suggest carcinoid syndrome or there is suspicion of serotonin secretion.

Treatment options for rectal neuroendocrine cancer

Treatment depends on tumour size, grade, depth of invasion, and whether the cancer has spread. Small, low-risk tumours can often be managed by a gastroenterologist or colorectal surgeon. However, more complex cases, such as larger tumours, higher-grade disease, incomplete resection, or metastatic disease, , should be reviewed by a specialist multidisciplinary team. This may include a gastroenterologist, colorectal surgeon, medical oncologist, nuclear medicine specialist, radiologist, and pathologist.

Endoscopic resection

Small, well-differentiated rectal NETs under 10 mm that are confined to the inner layers of the rectal wall can usually be completely removed using advanced endoscopic techniques. The two main approaches are Endoscopic Mucosal Resection (EMR), in which fluid is injected beneath the lesion to lift it before removal using a wire loop, and Endoscopic Submucosal Dissection (ESD), a more technically demanding technique that allows complete removal of the lesion in one piece with confirmed pathological margins.

These tumours can often be successfully treated with endoscopic resection alone.Pathological examination of the removed specimen confirms whether the tumour has been completely removed with clear margins.

Surgical resection

Tumours greater than 20 mm, or those that have grown into the deeper muscular layers of the rectal wall or spread to nearby lymph nodes, typically require formal surgical resection. This involves removal of the affected section of rectum together with the relevant lymph nodes.

Tumours in the intermediate range of 10 to 20 mm are assessed individually, taking into account grade, depth of wall invasion on endorectal ultrasound, and the suitability of endoscopic versus surgical removal.

Somatostatin analogues

For advanced or metastatic well-differentiated rectal neuroendocrine tumours (NETs), monthly injections of somatostatin analogues such as octreotide or lanreotide may be used to help slow tumour growth.

Long-term use of somatostatin analogues can reduce digestive enzyme production and affect fat absorption in some people, and may increase the risk of gallstone formation. These potential side effects are monitored as part of routine follow-up.

Peptide receptor radionuclide therapy (PRRT)

PRRT delivers targeted radiation to neuroendocrine tumour cells by coupling a radioactive element to a molecule that binds to somatostatin receptors on the tumour surface. It may be considered for patients with advanced, inoperable, or metastatic well-differentiated rectal NETs that express somatostatin receptors on functional imaging. Lutetium-177 DOTATATE is PBS-listed in Australia for eligible gastroenteropancreatic NETs.

Chemotherapy and targeted therapies

For poorly differentiated neuroendocrine carcinomas (NECs), systemic chemotherapy is the primary treatment approach. Platinum-based chemotherapy regimens are typically used for high-grade poorly differentiated NECs.

For advanced well-differentiated G2 or G3 NETs, targeted therapies such as everolimus may be considered in selected cases. Treatment decisions for advanced disease should always be guided by a specialist multidisciplinary team with expertise in neuroendocrine cancers.

Living with rectal neuroendocrine cancer

For many people with small, low-grade rectal neuroendocrine cancers that have been completely removed, the outlook is very good. However, living with rectal neuroendocrine cancer requires ongoing monitoring and, for those managing more advanced disease, continuing treatment and adjustment to daily life.

It is entirely normal to feel anxious or overwhelmed following a diagnosis, regardless of tumour size or grade. Psychological support, connection with others who have had similar experiences, and access to clear and reliable information all play an important role in wellbeing throughout the journey.

NeuroEndocrine Cancer Australia provides access to a specialist NET counsellor as part of its support services.

Dietary considerations

For most people with small rectal neuroendocrine cancers that have been completely removed endoscopically, specific dietary restrictions are not required. Those with more advanced disease, those experiencing bowel symptoms related to treatment, or those on long-term somatostatin analogues may benefit from individual dietary assessment and guidance.

A dietitian with experience in neuroendocrine cancer can help people manage any nutritional challenges, including fat malabsorption related to somatostatin analogue use, and optimise dietary intake throughout treatment and recovery.

NeuroEndocrine Cancer Australia provides access to a specialist NET dietitian as part of its support services.

Monitoring symptoms

Follow up after treatment for rectal neuroendocrine cancers depends on the tumour characteristics, including size, grade, depth of invasion, and completeness of removal. Ongoing monitoring may include assessment for any new or returning symptoms, including rectal bleeding, changes in bowel habits, rectal pain, or unexplained weight loss. Any new symptoms should be reported to the treating team promptly.

Supportive care and resources

Living with rectal neuroendocrine cancer at any stage can be emotionally challenging. Connecting with specialist support, peer networks, and reliable information makes a meaningful difference to quality of life and sense of control.

NeuroEndocrine Cancer Australia provides education, resources, advocacy, and access to specialist services for people affected by rectal neuroendocrine cancer and their families, including the NET Nurse service and specialist NET counsellor and dietitian.

Research and future directions

Research into rectal neuroendocrine cancer is advancing alongside the broader field of neuroendocrine tumour science, with improvements in endoscopic techniques, functional imaging, targeted therapies, and long-term survivorship strategies continuing to evolve.

Ongoing studies and clinical trials

Clinical trials are investigating novel treatments for advanced neuroendocrine tumours, including new targeted therapies, immunotherapy approaches, and refined PRRT delivery methods. Australia participates in international clinical trial networks for neuroendocrine cancers.

People with advanced or treatment-resistant rectal neuroendocrine cancer should speak with their treating team about whether any currently open clinical trials may be relevant.

Potential breakthroughs in rectal neuroendocrine cancer management

Future directions in rectal neuroendocrine cancer management include more refined endoscopic resection techniques for intermediate-sized tumours, improved tools for predicting which tumours carry a higher risk of aggressive behaviour, molecular profiling to guide personalised treatment selection, and better-defined long-term survivorship protocols for people who have been treated with endoscopic resection. Advances in functional imaging continue to improve the ability to detect and monitor disease throughout the body.

Rectal neuroendocrine cancer is a varied condition spanning a wide spectrum of behaviour and prognosis. While many people with small, low-grade rectal NETs can expect an excellent outcome with minimally invasive treatment, others with larger or more advanced tumours require specialist multidisciplinary care. Understanding the nature of the tumour, accessing specialist expertise, and engaging with ongoing follow-up are essential for achieving the best possible outcome.

For patients diagnosed with rectal neuroendocrine cancer, contact NeuroEndocrine Cancer Australia for comprehensive support and information through our NET Nurse service.