NEUROENDOCRINE CANCER OF THE
Neuroendocrine Neoplasm (NENs) is an umbrella term used to cover a group of cancers that start in neuroendocrine cells. These cancers may also be referred to as NETs, NECs, or even Carcinoids. NENs occur when neuroendocrine cells stop working normally and start to grow or behave abnormally.
There are 2 key types of NEN:
- NETs (neuroendocrine tumours) are called ‘well-differentiated’ and may be Grade 1, 2 or 3 (slow to rapid growth rate).
- NECs (neuroendocrine carcinomas) – are called ‘poorly differentiated’ and are usually Grade 3 (rapid growth rate.
To simplify, we use the term NENs throughout this page.
The rectum is the final segment of the large intestine that connects the colon to the anus. It stores waste produced in the colon until the body is ready to eliminate the waste through the process of defecation (having a poo!). It is a hollow muscular tube 6 – 8 inches (15 – 20 centimetres) in length and 2.5 inches in diameter at its widest point.
Although Rectal NENs are one of the most commonly diagnosed NENs (in part related to colon cancer screening investigations) they are amongst the least common colorectal cancers (<2%).
In the early stage the rectal NEN may present as a small polyp (less than 1 – 2 centimetres), or a flat doughnut shaped lesion. Larger polyps or lesions are possible, both with and without disease spread. In either case there are clear treatment and follow up protocols in place that will be discussed with you.
Not all cancers are the same or behave in the same way. Some may grow very slowly, may not have invaded nearby structures, or spread to other parts of the body at the time of diagnosis – but they have the potential to. However some may have already spread at the time of diagnosis.
The grade is the rate at which the NEN grows. You might see this referred to as ‘Ki67’ or ‘Mitotic Index’ mentioned in your clinic letters or medical reports. Grade 1 is slow-growing through to Grade 3, a more aggressive, rapidly growing disease.
Causes and potential risk factors for Neuroendocrine Cancer
We do not know exactly what causes Neuroendocrine Cancer – however it is important to follow advice in leading a healthy lifestyle: eat healthily, exercise and avoid smoking and too much alcohol.
Most Neuroendocrine Cancers do not run in families; however, a number of rare conditions may increase the risk of them developing. Therefore, if other members of the family have been diagnosed with cancer, or have a known genetic condition, it is important that you tell your specialist team about not only your personal medical history, but also any family medical illnesses or conditions.
We recommend speaking to your GP, and specialist team, if you have a genetic condition or strong family history of rectal cancer. They may refer you for an NHS genetic test, which will tell you if you have inherited one of the cancer-risk genes. The two most common inherited colorectal cancer syndromes are Lynch syndrome (hereditary nonpolyposis colorectal cancer (HNPCC)) and familial adenomatous polyposis (FAP).
Neuroendocrine Cancer of the Rectum is rare – and may not be associated with the above mentioned genetic alterations. However, if you do have a genetic alteration or strong family history of Rectal or Neuroendocrine Cancer – knowing this information may help your specialist team in planning your care and ensuring follow up is appropriate for you.
Symptoms that may or may not include Neuroendocrine Cancer associated syndromes
(Syndrome is where 2 or more related symptoms occur).
Symptoms of Neuroendocrine Cancer of the Rectum may include:
- Bleeding from the bottom (rectal bleeding)
- Itching and pain around the rectum and or anus
- Small lumps around the anus
- A discharge of mucus
- Loss of bowel control (bowel incontinence)
- A feeling that your rectum doesn’t empty completely or Tenesmus – a continual or recurrent feeling that you need to defecate / open your bowels
- Weakness or fatigue
- Unexplained weight loss
However, many people experience no symptoms at all in the early stages of the disease. When symptoms appear, they may be related to the cancer’s size and location.
Neuroendocrine Cancer of the Rectum is rarely associated with a Neuroendocrine associated syndrome.
Other, rarer symptoms, including Paraneoplastic syndrome and oncological emergencies, (a specific set of health concerns that can occur in any cancer), such as raised calcium levels (Hypercalcaemia), may occur.
Further information about Neuroendocrine Cancer associated and Paraneoplastic Syndromes – including Oncological emergencies – can be found here.
Tests that may be used for the diagnosis and / or monitoring of Neuroendocrine Cancer of the Rectum:
Blood and / or urine:
Full blood count
(B12 + serum Iron)
Liver and kidney function
Chromogranin A (and B)
Scans and further investigations:
Sigmoidoscopy / Colonoscopy +/- biopsy.
Contrast CT : chest/abdomen/pelvis
Gallium-Dotatate PET/CT (SRS SPECT/CT if Dotatate PET n/a)
FDG-PET – if High Grade / rapidly progressing disease.
Pathology (what can be seen through special tests under a microscope):
Differentiation and cellular morphology
Low molecular weight keratins
Prostatic acid phosphates.
The key aim of treatment, should be to help you have the best possible care and quality of life – by ensuring access to appropriate treatment, management of symptoms and addressing what’s most important to you
Treatment options will depend on the type, position and size of your cancer – and whether (and to where) it has spread.
It will also depend on whether you have any other health concerns and / or illnesses and your general health and fitness.
One or more of the approaches below may be suggested:
- Control of your disease, by slowing or stopping further growth and / or spread
- Palliation, or easing, of any symptoms you may be experiencing.
Monitoring through clinic review, bloods and scans, can be used to assess how well treatment is working or in periods between treatments (which may be months/years).
As not everyone will need to be on treatment – surveillance can be used to check your cancer and general health for any signs of change that may mean that a treatment might need to be considered. All treatments have possible side-effects, therefore, it is important to know when treatment may be helpful for you or not.
Will depend on site, size, position and spread of your Neuroendocrine Cancer. Some rectal cancers develop within polyps – others form solid tumours.
A polyp is a small cell clump that develops in 2 ways : Pedunculated polyps hang from a short stalk. Sessile polyps are flat and they grow directly out of the surrounding tissue.
If your neuroendocrine cancer develops within a polyp you may be able to have it removed by:
Polyps are removed during endoscopy using hot or cold forceps or a snare.
EndoMucosal Resection (EMR):
An endoscope is introduced to the site of the polyp. Using a small needle a fluid is injected underneath to raise the polyp creating a safe field to remove it using a snare. The area is then cauterised (to stop bleeding).
Endocopic Submucosal Dissection (ESD):
The procedure is similar to EMR but uses a small knife, rather than a snare, to remove the polyp, cauterising blood vessels at the same time to prevent bleeding.
If it is a large polyp or small tumour you may be able to have it removed by:
Transanal Mucosal Surgery (TEMS):
Using a specially designed microscope and instruments, this procedure allows surgery to be performed through the anus (back passage) inside the rectum.
TransAnal Minimally Invasive Surgery (TAMIS):
A specialised laparoscopic surgery port is placed into the anus. The laparoscope and instruments required to carry out the procedure are passed through the port to the rectum, so that the polyp or tumour can be surgically removed.
Larger or more invasive disease will require more complex surgery:
Total Mesorectal Excision (TME):
Is surgery to remove the rectum and sigmoid colon, including the blood supply and associated lymph glands. This procedure may result in a temporary or permanent colostomy dependent on whether is possible to rejoin the end of the healthy bowel to the anus.
Is surgery to remove the lower part of your (descending) colon, sigmoid, rectum and anus – along with associated lymph glands. This procedure results in a permanent colostomy.
*A colostomy is formed by bringing part of your colon (large bowel) or the end or loop of ileum (small bowel) out on to the surface of your abdomen to form a stoma (an opening) – and may be temporary or permanent – depending on how much bowel is removed, how much you have left and how healthy your remaining bowel is. Waste passes out of the stoma and is collected in an external pouch (known as a stoma bag). if your colostomy is temporary, further surgery make take place at a later date, to rejoin your bowel and close the stoma – this is called a stoma reversal.
Somatostatin analogues (SSAs):
Can be used to help regulate the secretion of hormones if abnormal levels are being produced. SSAs may also be used to slow down growth rate in low to moderate grade ‘well-differentiated’ neuroendocrine cancer (NET).
Can be given orally (in tablets) or Intravenously (through a vein) to slow tumour growth or try to reduce tumour size. This may be the first line therapy in high grade disease – particularly “poorly-differentiated’ NEC or in combination with other treatments. Chemotherapy may also be used to increase tumour cell sensitivity to radiation therapies.
Targeted Molecular Therapies:
Can be given orally (in tablets) or Intravenously (through a vein) to slow tumour growth or try to reduce tumour size.
Peptide receptor radionuclide therapy (PRRT):
May also be called Radioligand Therapy – uses targeted radiation to treat neuroendocrine cancer cells. Can be used in some patients who have had a ‘positive’ Octeotide or Gallium scan (‘receptor positive’ disease).
Is sometimes given after surgery, or as a primary treatment, to kill any cancer cells that might remain there. It may also be used for cancer that has spread beyond the primary site, in particular if disease has spread to the bones – here it is used to help control growth of any spread and alleviate bone pain.
Through techniques such as embolisation or ablation – can be used to treat Neuroendocrine Cancer that may develop in the the liver and / or lung(s).
Clinical research and safe new treatment development is essential to provide best care for those with Neuroendocrine Cancer – we need to know that treatments not only work but work safely. There are several phases of trial therapy – further information can be found here. Each trial will have specific criteria in regards to patient suitability – this can be discussed with your clinical team. You do not have take part in a trial – participation is voluntary.
Managing symptoms, including pain, is an important part of total care – and therefore occurs throughout care, not just at ‘end-of-life’. Symptom control or ‘palliation’ refers to what is used to alleviate or reduce the impact your cancer, other health issues and /or treatments may be having on you and your physical and mental health. It can include anything from simple medication and / or a combination of some of the treatments mentioned above to counselling and practical support.
There are expert agreed guidelines regarding how and when follow up should occur, however, in practice this varies and often with good reason. Follow up should be expert informed & evidence /research based but also tailored to you and what is appropriate for your best care.
Following surgery/endoscopic resection – for minimum 10 years:
- G1/2 <1cm: no lymph nodes, no evidence of invasion: there is no data re recommended follow up.
- G3 <1cm: annual follow up with colonoscopy.
- G1/2 1-2cm: annual follow up with colonoscopy.
- Biochemistry alongside colonoscopy/scan.
ALL Neuroendocrine Cancers >2cm require ongoing follow up – minimum 10 years (nb metastatic disease has been seen beyond this time):
- G1/2: annual colonoscopy + CT + biochemistry.
- G3: 4 – 6 monthly colonoscopy + CT + biochemistry for the first year, then annually.
If liver tumours present – for MRI or contrast CT concurrent with follow up timings.
- Follow up as per guidelines – but should be guided by prognosis, expected treatment efficacy and treatment related toxicity. Your health, well-being, physical activity, informed choice and preference for ongoing care as well as aim of treatment should be reviewed and discussed to best plan care.