Supporting the

Neuroendocrine Cancer Community

Cancer of the Unknown Primary

Overview

Although, it is usually possible to work out where a cancer has started, by assessing symptoms and reviewing tests and scans, sometimes confirmation is not always possible. 

This may be due the way Neuroendocrine Cancers develop, they start at a size similar to a grain of sand – and make take many months, possibly years to develop into the size that maybe detectable by scans.

Despite small size (sometimes simply a few cells) Neuroendocrine Cancers may still spread (metastasise) – this does not necessarily indicate an aggressive nature, indeed it may occur as a result of chronicity (that is, the primary collection of cells have been there so long, that over time, one or cells may enter the blood or lymph system and travel elsewhere in the body – usually the liver).

Your medical team may classify your cancer as being of unknown origin – or CUP (Cancer of Unknown Primary).

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 a particular cancer runs in your family. They may refer you for an NHS genetic test, depending on the type of cancer and whether a test is available, which will tell you if you have inherited one of the cancer-risk genes.

Neuroendocrine Cancer of Unknown Primary is rare – and may not be associated with the above mentioned genetic alterations or family history. However, if you do have a genetic alteration or strong family history of 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).

Cancer of unknown primary may or may not produce symptoms, if they occur they will depend on the type and site of the primary.

They may, or may not, produce symptoms that are related to a Neuroendocrine associated syndrome (which may help in identifying the likely primary site).

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 Known Primary.

Investigations should be guided by presentation – that is, clinical signs and symptoms – and need to include assessing all potential primary sites.

Pancreas, lung, right hemi-colon and small intestine are the most frequently occurring primary sites for Neuroendocrine Cancer
Carcinoid syndrome can be associated with distant metastases (especially where secondary spread is identified within the liver).

Blood and / or urine:

Full blood count
Liver and kidney function
B12/Iron/Ferritin/Folate
Chromogranin A
Gut Hormone profile
Calcium
Thyroid function tests
Urinary or serum 5HiAA (serotonin).
CEA, Beta-HCG, Alpha-FP, LDH, PSA, Ca19-9, Ca-125

Scans:

CT chest, abdomen and pelvis and/ or CT chest & MRI abdomen and pelvis
Octreotide (SPECT) or Gallium-Dotatate PET/CT
FDG-PET
Bone scintigraphy – if bone disease is present +/- suspected

Endoscopy:

As guided by clinical presentation / biomarker result

Pathology (what can be seen through special tests under a microscope):

Differentiation and cellular morphology
Synaptophysin
Chromogranin
Ki67
Additional IHC as clinically indicated

 

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:

  • Surgery
  • Control of your disease, by slowing or stopping further growth and / or spread
  • Palliation, or easing, of any symptoms you may be experiencing.

Surveillance:
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.

Surgery:
To remove, partially remove or bypass neuroendocrine cancer and / or secondary sites of disease (metastases).

Non-surgical treatments:

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).

Chemotherapy:
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).

Radiotherapy:
Is sometimes given after surgery 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

Endoscopic procedure:
Treatment given via endoscopy – for example, removal of a stomach or rectal polyp.

Interventional radiology:
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).

Irreversible electroporation (IRE also known as Nanoknife):
Is a relatively novel therapy, not widely available, that uses a strong electric current to kill cancer cells. It may be particularly useful in treating primary or secondary disease when surgery, or other ablation techniques, are risky because tumours are located too close to structures such as major blood vessels.

Clinical Trials:
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 in our “Clinical Trials” factsheet. 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.

Symptom Control:
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.

Follow up as per histology, grading and staging of disease – guided by results as per probable primary site.

Frequency as per disease status and potential for treatment.

Advanced disease:
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.

 

About Us

Neuroendocrine Cancer UK is a UK wide charity solely dedicated to providing support and information to those affected by Neuroendocrine Cancer.

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