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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.

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. When cancer is found in one or more secondary sites but it is not clear from the test results where the cancer began, the cancer is usually called
cancer of unknown primary, or CUP. In some cases, health professionals may also call it metastasis of unknown origin (MUO), metastatic malignancy of unknown primary, or occult primary cancer.

CUP is considered advanced cancer. This means that your treatment may focus on controlling symptoms and helping you plan the best possible future care for yourself. In certain cases, doctors may actively treat the cancer while still making sure that symptoms are well managed and you have planned your future
care. Your doctor will discuss the best approaches for you.

How can doctors tell it is a secondary cancer?

To diagnose secondary cancer, a specialist doctor called a pathologist looks at the cancer cells under a microscope. The pathologist 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, the cancer cells might have come from a number of places.

Why can’t the primary cancer be found?

There could be several reasons why your doctors cannot find the primary cancer. If you are diagnosed with CUP, it may be that:

  • the secondary cancer has grown and spread quickly, but the primary cancer is still too small to be seen on scans
  • your immune system has destroyed the primary cancer, but not the secondary cancer
  • the primary cancer cannot be seen on x-rays, scans or endoscopies because it is hidden by a secondary cancer that has grown close to it
  • the primary cancer was removed during surgery for another condition without realising the cancer was there, so some cancer cells remained behind and have  since spread
  • the primary cancer may have been too small to be found in tests – a single cell may have changed into cancerous cells and then spread through the body.

Does it matter that the primary cancer can’t be found?

Finding the primary cancer helps doctors decide what treatment to recommend and gives 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 plan the treatment. They will also try to learn as much as possible about the spread of the cancer, your symptoms and your medical history.

Will I need lots of tests?

Most people with a new diagnosis of cancer need several tests. 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. 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 your treatment. If you do decide not to have further tests, you may find your family and friends encourage you to continue having tests. This can be challenging, and it may help to explain your reasoning 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.

adenocarcinomadevelops from mucusproducing (glandular) cells, which form part of the lining of many organs; may have started in the bowel, lungs, liver, pancreas, prostate or stomach; makes up about 50% of CUP cases.
squamous cell carcinoma (SCC)develops from squamous cells, which are thin, flat cells normally found on the surface of the skin or in the lining of some organs; may have started in the head and neck area, oesophagus, lungs, pancreas, cervix, vagina or skin; makes up about 10-15% of CUP cases.
neuroendocrine carcinomadevelops from specialised nerve cells that sometimes produce hormones; may have started in the gastrointestinal tract or the pancreas and less commonly in the lungs or gynaecological or urinary systems; makes up about 3% of CUP cases.
poorly differentiated carcinomathere is enough detail to tell that the cells are a carcinoma, but not enough detail to work out the type of cancer or where the primary site may have been; makes up about 30% of CUP cases.
undifferentiated neoplasmthe cells can be identified as cancerous, but it is not possible to work out whether they are a carcinoma or another form of cancer such as a sarcoma or melanoma (neoplasm is another word for tumour) and not enough detail to work out where the primary site may have been; makes up about 5% of CUP cases.

How common is CUP?

CUP is a rare diagnosis. 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.

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Understanding Cancer of Unknown Primary

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This information is reviewed by

This information was last updated June 2020 by the following expert content reviewers: Prof Linda Mileshkin, Medical Oncologist, Clinical Researcher, Peter MacCallum Cancer Centre, VIC; Christine Bradfield, Consumer; Cindy Bryant, Consumer; Dr Maria Cigolini, Head, Department of Palliative Medicine, Royal Prince Alfred Hospital, and Clinical Lecturer, The University of Sydney, NSW; Mary Duffy, Advanced Practice Nurse and Nurse Coordinator, Lung Service, Peter MacCallum Cancer Centre, VIC; Karen Hall, 13 11 20 Consultant, Cancer Council SA; Dr Andrew Oar, Radiation Oncologist, Icon Cancer Centre, Gold Coast University Hospital, QLD; Dr Siobhan O’Neill, Medical Oncologist, Nelune Comprehensive Cancer Centre, NSW; Prof Penelope Schofield, Department of Psychological Sciences and the Iverson Health Innovation Research Institute, Swinburne University of Technology, and Head, Behavioural Science in Cancer, Peter MacCallum Cancer Centre, VIC; Frank Stoss, Consumer.