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What is cancer of unknown primary?

Cancer of unknown primary (CUP) is when cancer cells are found in the body but the place the cancer began is not known. This means it is a secondary cancer that has spread to a new place from an unknown primary cancer somewhere else in the body.

With CUP, secondary cancers are commonly found in the liver, lung, abdomen, bones and lymph nodes, although they can grow in any part of the body.

Health professionals may also call CUP metastatic malignancy of unknown primary or occult primary cancer.

To diagnose secondary cancer, a specialist doctor called a pathologist looks at the cancer cells under a microscope. They can see that the cancer cells  do not belong to the surrounding tissue, and this can be confirmed by further tests on the cells. With CUP, there are many different places in the body the cancer cells might have started.

CUP is not very common. There are about 2600 new cases of CUP diagnosed each year in Australia. CUP is more likely to occur in people over the age of 60.

For most people diagnosed with cancer, the primary cancer is easy to identify. Doctors conduct tests to find out where the cancer started to grow and to see if it has spread. Sometimes, however, cancer is found in one or more secondary sites and test results can’t show where the cancer began.

Reasons why your doctors cannot find the primary cancer include:

  • the secondary cancer has grown quickly, but the primary cancer is still too small to be seen on scans or found on tests
  • your immune system has destroyed the primary cancer, but not the secondary cancer
  • the primary cancer can’t be seen on x-rays, imaging scans or endoscopies because it’s hidden by a secondary cancer that has grown close to or over it
  • the cancer may be found in many parts of the body, but it isn’t clear from the scans or pathology tests which is the primary cancer.

Finding the primary cancer can help doctors decide what treatment to recommend and give them a better idea of how the cancer is likely to respond to treatment. If the primary cancer can’t be found, tests on cells from the secondary cancer can often suggest what the primary cancer is most likely to be. This helps your doctor to plan treatment.

It can be frightening to be diagnosed with CUP, but there are treatments available. Your doctor will discuss the best options for you. The aim of treatment may be to:

  • Slow the cancer’s growth or spread and prolong overall survival – In many cases, doctors may actively treat the cancer but not be able to cure it. In some cases, CUP presents in a pattern that is very like cancers from a known primary and can respond well to the same kind of treatment, even though the primary can’t be found.
  • Relieve symptoms and maintain quality of life – CUP usually presents as advanced cancer, so treatment may focus on controlling symptoms and helping you plan the best possible future care for yourself. This is known as palliative treatment.
  • Remove as much of the cancer as possible – In a small number of cases, CUP is found as a small area of cancer that may be able to be removed with surgery or high-dose radiation.

Most people with a new diagnosis of cancer need several tests to find out how far the cancer has spread throughout the body.

People with CUP may need extra tests to try to find where the cancer started. The tests may take time and be tiring, particularly if you are feeling  unwell. Waiting for the results can be a stressful time. You may also feel frustrated if the tests don’t find the primary cancer. Your doctors will only suggest tests that they think are needed. It is okay to ask your doctors to explain the tests and the difference the results will make to your care. You may also want to ask if there are any specialised tests available at another hospital or treatment centre that may help find the primary cancer.

At some point, your doctors may decide that having more tests won’t help find the primary cancer and it would be better to focus on starting treatment. Even if you decide not to have more tests, your family and friends may encourage you to continue having tests. This can be challenging. It may help to explain why you want to stop testing and share this information with them. Your medical team can provide support with these discussions.

Are there different types of CUP?

Even if tests can’t find where the cancer started, your doctor will try to work out what type of cell the cancer developed from. Knowing the type of cell helps  doctors work out what sort of treatment is most likely to be helpful.

Most cancers are cancers of the epithelial cells, which are found in the lining of the skin and internal organs. These cancers are known as carcinomas. In most people with CUP, doctors can tell that they have some sort of carcinoma. There are different types of carcinoma depending on which type of epithelial cell is affected. Your doctor will explain the type of CUP you have.

Types of cancer of unknown primary (CUP)

Adenocarcinoma

  • Which cells are affected? – mucus-producing (glandular) cells, which form part of the lining of many organs.
  • Where might it have started? – bowel; breast; liver; lung; oesophagus; ovary; pancreas; prostate; uterus.
  • How common is it? – makes up about 60% of CUP cases.

Squamous Cell Carcinoma (SCC)

  • Which cells are affected? – squamous cells, which are thin, flat cells normally found on the surface of the skin or in the lining of some organs.
  • Where might it have started? – anus; cervix; head and neck area; lung; oesophagus; skin; vagina.
  • How common is it? – makes up about 5% of CUP cases.

Neuroendocrine Carcinoma

  • Which cells are affected? – specialised neuroendocrine cells found throughout the body that sometimes produce hormones.
  • Where might it have started? – bowel; oesophagus; pancreas; stomach; less commonly may start elsewhere such as in the lungs or gynaecological or urinary systems.
  • How common is it? – makes up about 5% of CUP cases.

Poorly Differentiated Carcinoma

  • Which cells are affected? – tests show that the cancer cells are a carcinoma, but don’t show the specific type of epithelial cell affected.
  • Where might it have started? – not enough detail to suggest where the primary site may have been.
  • How common is it? – makes up about 25% of CUP cases.

Undifferentiated Neoplasm (tumour)

  • Which cells are affected? – unknown – tests show that the cells are cancerous, but not whether they are a carcinoma or another form of cancer (such as a  sarcoma or melanoma).
  • Where might it have started? – not enough detail to suggest where the primary site may have been.
  • How common is it? – makes up about 5% of CUP cases.

Featured resources

Cancer of Unknown Primary - Your guide to best cancer care

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Understanding Cancer of Unknown Primary

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This information is reviewed by

This information was last updated September 2022 by the following expert content reviewers: Prof Chris Karapetis, Network Clinical Director (Cancer Services), Southern Adelaide Local Health Network, Head, Department of Medical Oncology, and Director, Clinical Research in Medical Oncology, Flinders Medical Centre and Flinders University, SA; Dr Amey Aurangabadkar, Radiologist, Illawarra Radiology Group, NSW; Clare Brophy, Consumer; Prof Katherine Clark, Clinical Director of Palliative Care, NSLHD Supportive and Palliative Care Network, Northern Sydney Cancer Centre, Royal North Shore Hospital, NSW; Prof Wendy Cooper, Senior Staff Specialist, Tissue Pathology and Diagnostic Oncology, NSW Health Pathology, Royal Prince Alfred Hospital, NSW; A/Prof Richard Gallagher, Head and Neck Surgeon, Director of Cancer Services and Head and Neck Cancer Services, St Vincent’s Health Network, NSW; Dr Chloe Georgiou, Oncology Research Fellow, Australian Rare Cancer Portal, and Oncology Trials Fellow, Bendigo Health Cancer Centre, VIC; Dr Susan Harden, Radiation Oncologist, Peter MacCallum Cancer Centre, VIC; Justin Hargreaves, Medical Oncology Nurse Practitioner, Bendigo Health Cancer Centre, VIC; Dr Laura Kirsten, Principal Clinical Psychologist, Nepean Cancer Care Centre, NSW; Prof Linda Mileshkin, Medical Oncologist, Peter MacCallum Cancer Centre, VIC; Caitriona Nienaber, 13 11 20 Consultant, Cancer Council WA.