People react in all kinds of ways when they are told they have cancer. Maybe you fell silent or couldn’t stop asking questions. Maybe you wanted to be alone or wanted your whole family around you. Maybe you felt numb or overwhelmed by emotion. Maybe you even felt relief. However you reacted is completely normal. There is no wrong or right way.
The situation with neuroendocrine cancer can be even more complicated because these types of tumors are often misdiagnosed initially or can take a long time to be correctly identified. It’s not at all unusual to have felt unwell for months or even years, before a neuroendocrine cancer is diagnosed, or to have been told that your symptoms are due to another condition, like irritable bowel syndrome, Crohn’s disease, gastritis, asthma or problems linked to the menopause or blood pressure (conditions that can mimic or mask neuroendocrine cancer or exist alongside it).
On the other hand, you may not have felt unwell at all and have received your diagnosis as a result of a routine health check.
As soon as you’re diagnosed with a neuroendocrine cancer, it’s vital to get the best possible advice and treatment from the right team of people. If you’re diagnosed with a neuroendocrine cancer, a specialist “NET” specific multidisciplinary team (”NET” MDT) should review your case on an ongoing basis. That does not mean you have to physically travel to a specialist center but a review of your case and advice is a minimum that should be expected. That MDT team will be made up of a range of clinical experts who specialize in neuroendocrine cancer.
Types of neuroendocrine cancer – NET/NEC
Cancer of unknown primary (CUP)
Cervix and Uterus
Testicles and Prostate
Before and after you’re diagnosed, tests become a regular part of your life. Here is what is likely to happen and why. Diagnosis isn’t straightforward. The NET/NEC is often small, starting out the size of a grain of sand and often not visible to the most accurate scans until it gets to about half a centimeter across or the size of a pea. NET/NECs can occur in various parts of your body and spread to different places too, so finding them and identifying where they started can, on occasion, be difficult. Because of this, you may well have a number of tests before your diagnosis is confirmed – including specialist tests to ensure the evidence is conclusive. Once you have a diagnosis, some of the tests you have undergone will be used to monitor your health and the effects of your treatment.
Various blood tests are used to help diagnose NET/NEC, monitor your health and to see how you’re responding to treatment. Some can be done at the GP’s office, others need to be done in hospitals or specialist treatment centers. Your care team will let you know what to expect before any blood test.
1-Fasting gut hormone profile
More commonly used in syndromic pancreatic or duodenal NET/NEC. This is a blood test to help diagnose what type of syndromic NET/NEC you might have – in particular the specific hormone your NET/NEC is over-producing. For example, gastrin in pancreatic or duodenal gastrinomas. You’ll need to drink only water and avoid food for six hours beforehand. You can keep taking most medications as normal and do everything you usually do afterwards, but please check for any exceptions with your care team.
Chromogranin A and B are proteins often released by abnormal neuroendocrine cells. Doctors can test for them using the same sample that’s taken for a gut hormone profile, but there’s also a separate test for chromogranins alone, for those who do not need a gut hormone test, that doesn’t involve fasting beforehand.
High levels of chromogranins in your blood can indicate a NET/NEC, but they can be found in other conditions too. Results typically take a few weeks to come through, and you may need to have a follow-up chromogranin A and B test to help your care team gain a clearer picture of exactly what your situation is.
NB: It is not unusual for chromogranins to alter slightly – rise or fall by about 10% – between checks. This does not necessarily indicate a change in your NET/NEC, it could be due to something as simple as the time of day the blood sample was taken.
Please note that the laboratory tests are not 100% – there are other conditions that may cause unusual results or alterations – also your NET/NEC may not cause any irregularities in your blood or urine, so a normal result may not mean you don’t have neuroendocrine cancer. However, they are incredibly useful, in combination with other tests, to lead to an accurate diagnosis – and, if abnormal – can be useful as a monitoring tool over time and during/after treatment.
Other tests you may have:
- Full blood count, which measures the red blood cells, white blood cells and platelets in your blood, and can help your care team measure your general health and check for problems like anaemia. Iron, B12, ferritin and folate, which can check for and monitor certain types of anaemia. Kidney function test, which measures waste products, salts and potassium in your blood to show how well your kidneys are working.
- Calcium, corrected calcium and vitamin D, which can measure your bone health, monitor calcium levels and identify causes for some symptoms related to neuroendocrine cancer.
- Liver function test, which measures enzymes and proteins produced by the liver to check how well your liver is working.
- Pituitary hormone screen, which measures levels of hormones to show how your pituitary gland is functioning.
- PTH and blood calcium, which can be used a screening test for MEN-1 syndrome.
- Calcitonin, which checks for a hormone that can be released by MTCs
- NT-proBNP, which checks for signs of carcinoid heart disease.
- Thyroid function test, which assesses the condition of your thyroid by measuring levels of various hormones: it can prove or exclude under or active thyroid function.
This isn’t an exhaustive list. Your care team can let you know about any other blood tests you might need and answer any questions you might have.
If your doctor wants to check whether your NET/ NEC is over-releasing serotonin, you may be asked to undertake a “spot” or 24-hour urine collection. Excess serotonin is excreted from the body, in urine, as a substance called 5HIAA. Why is it done? Some NETs/NECs will produce abnormally high levels of serotonin – (which has, until recently, been difficult to measure by blood test*) this is broken down by the body and excreted, as 5HIAA, in urine. So, by testing for 5HiAA, your doctor can work out the level of serotonin in your body, which can help confirm your diagnosis. It may also be used to monitor carcinoid syndrome. NB: as with blood tests, urinary 5HIAA on its own, is not completely diagnostic – and levels can be altered by other conditions or even certain foods!
What is involved? “Spot” test is like giving a routine urine sample – no preparation required. For a 24-hour urine test – you will be given a large bottle/container that will have a small amount of powdered preservative in it and be asked to collect all of the urine you pass over a continuous 24-hour period. You will be given an advice sheet that will give you instructions on how to do this. It should also advise you on any foods or medications you should avoid taking in the 24-48 hours before starting the collection and the 24 hours during the collection. Certain foods, drinks and medications can lead to false positives – please check with your doctor/nurse.
You’ll also be asked to avoid taking some cough, cold and flu medicines for up to a week beforehand. Your care team will let you know more about that.
You don’t need to avoid these foods and drinks permanently – just before and during the 5HIAA test.
Some teams are now using a quicker way of measuring 5HIAA, which doesn’t involve collecting urine over 24 hours. They can use a random urine or blood sample, which can be done on the day of your appointment – which doesn’t need you to avoid any foods, drinks or medications.
Scans are done to create 2D and 3D images of NET/NEC and the areas around them. Some are done in radiology departments, others in nuclear medicine departments.
There are different reasons for different scans to be used, these are:
- detecting the primary tumor in a patient
- assessing extent of disease
- assessing response to treatment
- follow up after an initial diagnosis and/or treatment
Ultrasound scan – Why is it done?
An ultrasound (US) scan is a painless test that uses sound waves to create images of organs and structures inside your body. It is a very commonly used test. As it uses sound waves and not radiation, it is thought to be very safe. Certain ultrasound scans are used to look at blood or fluids flowing through the body. An ultrasound might also be used to check for gallstones, which can be a risk if you’re given somatostatin analogues as a treatment.
What is involved? You’ll usually be asked not to eat or drink anything for six hours before an ultrasound to make sure the picture is as clear as possible. NB: you may not need to do this if you have had your gallbladder removed OR if you are diabetic – please check with the department beforehand. Before the scan, a gel is spread on the area to be scanned. A hand-held ultrasound scanner is then gently pressed on the area, creating high frequency sound waves that help to build a real-time picture of your internal organs on a nearby screen.
CT scan – Why is it done?
By taking pictures of the inside of your body from a variety of angles, a CT scan (also called a CAT scan) can build up a very detailed picture of the location and size of your organs and the structures around it. They are used to check for abnormalities such as a tumor or enlarged lymph nodes. Regular scans can also help to track whether a tumor is growing or not, whether new tumors are developing and how well your body is recovering after treatment for example after surgery.
What is involved? During the scan you lie on a flat bed that slides slowly backwards and forwards through a large circular machine. The scan usually takes around 15-30 minutes, and you’ll need to lie still for that time. The technician running the scan will be in a separate room, but you’ll be able to speak to them through an intercom. Depending on which area of your body is being scanned, you may need to drink a liquid or have an injection beforehand to help increase the contrast of the scan. And you may need to avoid eating and drinking for a set time in preparation – check beforehand if you haven’t been given any information.
MRI scan – Why is it done?
Like a CT scan, an MRI scan builds up a detailed picture of the organs and structures of the body using a series of cross-sectional images. The difference is that an MRI uses magnetic fields and radio waves to take pictures and a CT scan uses X-rays.
ALERT: the scan uses magnets so please tell your care team BEFORE an MRI is asked for if you have a pacemaker or any metal pins or plates in your body – an alternative form of imaging may be required for you. For some tumors and some parts of the body, a CT scan produces clearer results. For others, an MRI scan is the preferred option. An MRI is particularly good at showing the liver, brain and spine.
What is involved? An MRI scanner is a large tube, and throughout the scan you lie on a flat bed that’s moved inside the tube – lying either head first or feet first, depending on which part of you is being scanned. The scan usually lasts between 15 and 90 minutes. The scanner is operated by a radiographer in a separate room, who you’ll be able to talk to throughout the scan. They can see you through a TV screen too. It can be noisy, so you’ll probably be given headphones or earplugs to block out the banging and tapping sounds. Some people do find being inside an MRI scanner claustrophobic. If you’re worried, make sure you chat to your care team beforehand and let the radiographer know how you’re feeling. There’s nothing to be embarrassed about and people can only help if they know of your concerns.
NB: You may be able to go in feet first regardless of which part of you is being scanned, which can help minimize claustrophobia. Unfortunately, only a few centers have open MRI scanners, so you could ask about that too.
Nuclear medicine scans
You might also hear these called ‘functional’ scans. Substances, called radioactive labelled tracers or isotopes are used, that have attractions to certain tumor cells, to create images that can help diagnose and monitor NET/NEC. Although a radioactive tracer is used during functional scans, the amount of radiation that you are exposed to is low and it is usually short-lived. It is not enough to affect the normal body processes. However, there are risks due to the tracer: the radioactive substance may expose radiation to the foetus of a pregnant woman or to the infant of a woman who is breastfeeding. If you are pregnant or breastfeeding, please tell your doctor – There is a very small risk of an allergic reaction to the tracer.
Octreotide scan – Why is it done?
NET cells sometimes have receptors, on their surface, that attract a substance called octreotide. By injecting you with a radioactive octreotide ‘tracer’ and using a scanner that detects this tracer, doctors can follow the path of the octreotide and see if it gathers in a particular place. If it does, it means that the octreotide has latched onto the receptors of a NET. However, they won’t show up every NET, because not all NETs, especially high-grade poorly differentiated NECs, have the receptors needed to attract octreotide.
What is involved? An octreotide scan takes place over two days. On the first day you’re given a small injection of the radioactive octreotide tracer. Around four hours later, once the tracer has spread through your body, you have a scan lying down for around 90 minutes. The following day you have another scan. You’ll need to lie as still as possible during the scans, and might be asked to lie with your arms above your head or at your sides to get the clearest picture. After the scans, make sure you drink plenty of water to help flush the tracer out of your system.
mIBG scan – Why is it done?
mIBG scans are similar to the octreotide scan, previously described, but use a different radioactive tracer “mIBG” (iodine-123-meta-iodobenzylguanidine). It is best utilized for the diagnosis and monitoring of pheochromocytomas and paragangliomas due to the mIBG tracer attraction to these particular tumors.
What is involved? Just as you do with an octreotide scan, you have an injection of a tracer (in this case mIBG) and then two scans – one later that day and one the next day. The main difference with an mIBG scan is that because some of this tracer can be absorbed by your thyroid gland you may need to take need to take a substance called Lugol’s iodine or potassium iodate on the day before the injection, the day of the injection and the next day, to stop this happening.
There are two main types of PET scan used to investigate and monitor NET/ NEC – FDG-PET and Gallium-PET. Currently, many PET scanners also include a conventional computed tomography (CT) scanner. This allows images of both anatomy (CT) and function (PET) to be taken during the same examination. Not all hospitals have PET scanners, so your nearest one may not be close to home.
FDG-PET – Why is it done?
A PET scan uses a small amount of a radioactive drug, or tracer, to show differences between healthy tissue and diseased tissue. The most commonly used tracer is called FDG (fluorodeoxyglucose), so the test is sometimes called an FDG-PET scan. Before the PET scan, a small amount of FDG is injected and because cancer grows at a faster rate than most healthy tissue, cancer cells absorb more of the FDG. The PET scanner detects the radiation given off by the FDG and produces color-coded images of the body that show both normal and cancerous tissue. Best used in high grade neuroendocrine cancer.
What is involved? You will be given detailed instructions on how to prepare for your scan. As a rule, you will be advised not to eat anything for 6 hours prior to your scan but you should continue to drink water. It is advisable to wear loose comfortable clothing. Before your scan, you will be given an injection of the radioactive tracer drug. The tracer takes around an hour to spread through your body. Once that’s happened, you’ll be asked to lie on a scanner.
The scan takes around an hour, and you’ll need to lie as still as possible during that time.
68Ga-DOTATATE/DOTATOC PET/CT – Why is it done?
68Ga-DOTATATE/DOTATOC PET/CT scans use the radioactive tracer Gallium-68, rather than the FDG-18 previously described. Scans with Gallium-68 take less time than Octreotide scans, require less tracer, produce results more quickly and create a more detailed picture of how neuroendocrine cancer is developing and what it looks like. 68Ga-DOTATATE PET/CT has been reviewed and evaluated as the most sensitive exam to detect well-differentiated NETs. It is rapidly replacing Octreotide scans in specialist NET centers due to its improved accuracy, sensitivity, shortened time, less tracer and lower allergy risk.
What is involved? Having a Gallium-68 scan is similar to having an FDG-PET scan. The main difference between the PET scans is the uptake according to tumor activity – FDG is more sensitive for high grade NET/NEC, Gallium68 is better for low to moderate and well differentiated NETs. You will be given detailed instructions on how to prepare for your scan. A general rule is to not eat anything for at least 4 hours before the scan. You will be encouraged to drink water. If you are receiving somatostatin analogues you may be advised to alter the day (or time if on short-acting) you have this injection. You will receive the tracer injection prior to your scan, this tracer can take up to an hour to spread through your body. Once that’s happened, you’ll be asked to lie on a flat bed, which is moved into a circular scanner.
The scan takes up to an hour, and you’ll need to lie as still as possible during that time.
Copper Cu 64 DOTATATE PET Scan (currently only approved in the US)
In 2020, the U.S. Food and Drug Administration approved a copper Cu 64 DOTATATE injection for use in positron emission tomography (PET) scans for certain kinds of neuroendocrine tumors (NETs). Diagnostic tracers like Cu 64 DOTATATE are used with PET scans and other functional imaging scans to improve how NETs are detected and staged.
The copper Cu 64 DOTATATE agent is a radiopharmaceutical tracer agent used in the localization of somatostatin receptor positive NETs in adults. According to phase 3 trials, Cu 64 DOTATATE demonstrated clinical sensitivity to allow clinicians to develop more precise treatment approaches for their patients who have NETs. In addition, less than 2% of study participants in clinical trials experienced adverse reactions to the agent, which typically included nausea, vomiting, and flushing. After FDA approval, the Cu 64 DOTATATE injection was immediately made available through nuclear pharmacies.
Copper Cu 64 DOTATATE PET scan is used in the same way and for the same reason as the gallium-68 DOTATATE scan. The difference, however, is that it has a longer half-life which means that the scan can be done in more remote centers, which improves access to the scan.
Bone scan – Why is it done?
Bone scans are used to check on your bone health. It’s not a routine test for NET/ NEC, and will only usually be done if you’ve had a history of bone problems such as osteoporosis, or if your care team suspects you may have spread to your bones.
What is involved? Before having a bone scan, you’re injected with a very small amount of a radioactive substance called a radionuclide. This tends to collect in areas where there is a lot of activity in the bone, and this activity shows up on a bone scanner. It can suggest that bones are damaged or repairing themselves, for example a healing fracture, as well as helping to assess bone density (a measure for assessing osteoporosis). After the injection, you’ll then need to wait for a few hours while it works its way through your body and into your bones. Having plenty to drink during this time will help, and taking an iPad, magazine or book with you is a good idea to help you pass the time. Once the radionuclide has spread, you’ll need to lie on a flat bed while a scanner called a gamma camera takes pictures of the whole of your skeleton.
Your body goes through the scanner, so let your radiographer know if you feel claustrophobic. The scan can take up to an hour.
If the radionuclide does gather in one place, that doesn’t always mean a NET/ NEC has spread to your bones. It could suggest osteoporosis, a new fracture (or break in the bone) or an old fracture that is either repairing itself or has healed.
Endoscopy – Why is it done?
Scans take pictures of your insides from outside your body. As detailed as they are, they don’t always give a full view of what is happening inside the hollow organs of the body – for example if doctors want to see inside your airways, stomach or bowel. In situations like that, endoscopies and endoscopic ultrasounds can be very useful. They can pick up problems in places like the stomach and duodenum that can be difficult to assess accurately on an MRI or CAT scan. And they mean your care team may be able to take tissue samples through the endoscope.
What is involved? During an endoscopy, a long, thin, flexible tube with a light and a video camera at one end (the endoscope) is used to transmit footage of the inside of your body to a TV screen. (In an endoscopic ultrasound the tube includes a small ultrasound probe). The endoscope, can be fed into your body through your mouth or nose (to look at your oesophagus, stomach and duodenum or to look at your lungs) or via your rectum (to look at your large bowel). The test can take up to an hour, and while it might sound unpleasant, it’s usually only slightly uncomfortable, rather than painful. You might be given a local anaesthetic to ease any pain or a sedative to help you relax, and your care team will let you know if there’s anything you need to do to prepare for the test, like not eating for a while for the upper scope or taking a preparation to help clear your bowels for the lower scope.
As with any test, if you’re worried, don’t keep it to yourself. Your care team will have a lot of experience of helping people cope with anxieties, and will have ideas that could help – like visiting the relevant department beforehand so you know what to expect.
Which endoscopy is that?
Bronchoscope looks inside the lungs and airways.
Endobronchial ultrasound (EBUS) looks inside the lungs and airways.
Endoscopic ultrasound (EUS) looks at the duodenum and pancreas.
Gastroscope looks inside the oesophagus, stomach and duodenum.
Colonoscope looks inside the large intestine.
Sigmoidoscopy looks inside the lower large intestine.
Rectal endoscopic ultrasound looks at the lower part of the large bowel.
Wireless capsule endoscopy or Video capsule endoscopy (WCE or VCE) Why is it done?
Capsule endoscopies give doctors a detailed, end-to-end look at your small bowel, which is one of the most difficult parts of the gastrointestinal tract to examine because of where it is, its length and complex shape. As such, WCEs/VCEs are particularly valuable for diagnosing small bowel NET/NEC.
What is involved? It might sound like science fiction, but if your doctor recommends this test you’ll swallow a capsule the size of a large vitamin pill that contains a color camera, battery, light source and transmitter. The camera then takes photos every second for eight hours and sends them wirelessly to a data recorder that you wear attached to a belt. The information from the recorder is uploaded to a computer for analysis.
You might be asked not to eat for a specific period before the test. Afterwards, the capsule comes out naturally when you open your bowels, and does not need to be retrieved.
Tissue sampling (also known as a biopsy or histology)
To monitor your treatment or a suspected NET/NEC, your care team might want to take a small piece of tissue, a collection of cells or some fluid from your tumor so it can be studied for the presence of cancer and activity of cells under a microscope.
Why is it done? Studying tissue under a microscope is often the only way to be absolutely sure of a cancer diagnosis. It can give clues about where a cancer started, what kind of cancer cells exist and how quickly they are multiplying. This knowledge can help doctors to recommend the best treatment. The pathologist may review the biopsy sample and give the tumor a proliferative index, i.e. a measure of the number of cells in the tumor that are dividing (proliferating). A proliferation index of less than 2% means that the tumor is very slow growing, while a value above 10% suggests faster growth. The test for determining a proliferation index is called Ki67 or MIB1.
What is involved? There are various ways of taking tissue samples. A biopsy is a medical procedure that involves taking a small sample of tissue so it can be examined under a microscope. A tissue sample can be taken from almost anywhere on or in your body, including the skin, organs and other structures. The term “biopsy” is often used to refer to both the act of taking the sample and the tissue sample itself.
Checking on the heart
Electrocardiogram (ECG) – Why is it done?
An ECG is used to gather information about your heart. It’s often used if you have a history of heart problems or to check your health before treatments such as surgery.
What is involved? An ECG is a simple test that might be carried out in hospital, at a clinic or at your GP surgery. Sticky sensors called electrodes are stuck to your chest, arms and legs and attached to an ECG machine that records your heart’s rate, rhythm and electrical activity (the signals the heart uses for each heartbeat).
Echocardiogram – Why is it done?
Often shortened to ‘echo,’ an echocardiogram is an ultrasound of the heart. It enables doctors to look in detail at the structure of the heart, and in particular at the heart valves. It can also measure how well the heart is pumping. Doctors often recommend an echo if they suspect you might have carcinoid heart disease, or if you or someone in your family has a history of heart problems.
If problems with heart valves are identified early enough, action can be taken in response – such as discussing with you the use of somatostatin analogues or the possibility of needing heart surgery to replace damaged valves. If you do have damaged valves you may need these treated before it is safe to go ahead with some of the treatments for your neuroendocrine cancer.
What is involved?
There are several ways to carry out an echo, but the most common is to first have sticky sensors called electrodes attached to your chest as you do in an ECG. These measure your heart rhythm during the test. An ultrasound probe is then moved across your chest to create a picture of your heart using sound waves. A gel is used, either on your chest or on the probe, to create the clearest possible images. The test usually lasts between 15 and 60 minutes.