Page last updated: October 2024
The information on this webpage was adapted from Understanding Cancer of Unknown Primary - A guide for people with cancer, their families and friends (2024 edition). This webpage was last updated in October 2024.
Expert content reviewers:
This information was developed based on international clinical practice guidelines. All updated content has been clinically reviewed by:
- 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.
This edition is based on the previous edition, which was reviewed by the following panel:
- Prof Chris Karapetis (see above)
- 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
Before CUP is diagnosed, you will usually see your GP, who will ask about your symptoms and medical history, examine you, send you for tests and refer you to a specialist doctor.
The specialist will arrange extra tests to work out whether you have primary or secondary cancer. If the tests show that the cancer is secondary, more tests will be done to try to find the primary cancer. The tests you have depend on your health and symptoms, the location of the secondary cancer and the suspected location of the primary cancer.
The diagnosis and treatment of CUP can be complex and you might need to travel to a specialist centre. Call Cancer Council 13 11 20 to ask about patient travel assistance that may be available to you.
Your guide to best cancer care
A lot can happen in a hurry when you’re diagnosed with cancer. The guide to best cancer care for liver cancer can help you make sense of what should happen.
It will help you with what questions to ask your health professionals to make sure you receive the best care at every step.
Read the guide
Tests used to find where the cancer started
- Blood and urine tests – samples of your blood and urine are sent to a laboratory to be checked for abnormal cells and chemicals called tumour markers
- Biopsy – a tissue sample is taken from a tumour, enlarged lymph node or bone marrow and sent to a laboratory for examination; tests on the sample can suggest the primary site
- Endoscopy – uses an instrument to look inside the body and take small tissue samples
- Imaging tests – x-rays, ultrasounds and other scans create images of the inside of the body; PET–CT scans have been shown to help find the primary site in new cases of CUP
If the tests find where the cancer started, the cancer is no longer an unknown primary. It will then be treated like the primary cancer type. For example, bowel cancer that has spread to the liver will be given the treatment for advanced bowel cancer.
Blood and urine tests
A full blood count is a test that checks the levels of red blood cells, white blood cells and platelets. Blood tests can also show how well the kidneys and liver are working. Urine and faeces (poo) may be tested to look for abnormal cells or bleeding coming from the bladder, kidneys or bowel.
Tumour markers
In some cases, blood, urine or tissue samples may be tested for tumour markers. These are proteins made by some cancer cells. High levels of tumour markers may suggest cancer.
However, other conditions can also raise the levels of tumour markers, and some people with cancer have normal levels. Tumour marker levels can’t be used on their own to diagnose the primary cancer, but they may suggest certain types of cancer for your doctors to look for.
Biopsy
A biopsy is when doctors remove a sample of cells or tissue from an area of the body. A specialist doctor called a pathologist examines the sample under a microscope to look for signs of cancer and work out what type of cell is affected. This can point to where in the body the cancer may have started.
For a biopsy, you will usually have a local anaesthetic to numb the area. In some cases, you may need a general anaesthetic, which puts you to sleep.
Ways of taking biopsies
There are different ways of taking a biopsy and you may need more than one type. A biopsy is often done using an ultrasound or CT scan to guide the needle to the correct place. You might not have a biopsy if the cancer is too hard to reach or if you are too unwell for the procedure.
Common types of biopsies used to diagnose cancer include:
- fine needle aspiration – removes cells using a thin needle
- core biopsy – removes tissue using a hollow needle
- incisional biopsy – cuts out part of a tumour
- excisional biopsy – cuts out the whole tumour.
Looking at the molecular level
In some cases, you may be offered extra tests on the biopsy sample. These are called molecular or genomic tests, and they look for gene changes and other features in the cancer cells that may be causing them to multiply and grow. The results may suggest what the primary cancer is most likely to be and which targeted therapy drugs may work best to treat it.
Molecular testing for CUP is usually not covered by Medicare, which can make it expensive. Check what costs are involved and how helpful it would be. If you are having molecular testing as part of a clinical trial, the costs may be covered. Ask your cancer specialists for more information about these specialised tests.
Endoscopy
This procedure is used to look inside the body for any abnormal areas. It is done with an endoscope – a thin, flexible tube with a light and camera on the end. The endoscope is put into the body through a natural opening (such as the mouth) or a small cut made by the surgeon.
The camera projects images onto a monitor so the doctor can see inside the body. If they see something suspicious, they can also take a tissue sample (biopsy) using the endoscope.
Common types of endoscopy
Type of endoscopy
|
Part of the body tested |
Where the tube is inserted |
| bronchoscopy or endobronchial ultrasound (EBUS) |
lungs or respiratory tract (airways) |
mouth or nose |
| colonoscopy |
colon (large bowel) |
anus |
| colposcopy |
vagina and cervix |
placed outside the vulva and vagina, held open by a speculum |
| cystoscopy |
bladder |
urethra |
| gastroscopy |
oesophagus, stomach and first part of the small bowel |
mouth |
| hysteroscopy |
uterus (womb) |
vagina |
| laparoscopy |
abdominal cavity, liver, bowel, uterus and ovaries |
small cuts in the abdomen |
| laryngoscopy |
larynx (voice box) |
mouth |
| sigmoidoscopy |
lower part of the colon (large bowel) |
anus |
| thoracoscopy |
lungs |
small cut in the chest |
Imaging tests
These scans create images of the inside of your body and provide different types of information. Your doctors will recommend the most useful scans for your situation. Ask your doctor or imaging centre what you will have to pay and whether Medicare covers the cost.
Before having scans, tell the doctor if you have any allergies or have had a reaction to dyes during previous scans. You should also let them know if you have diabetes or kidney disease, or are pregnant or breastfeeding.
X-ray
- This test creates pictures of the inside of the body.
- X-rays may be taken of the chest and other parts of the body.
- For some types of x-rays, a dye (contrast) is used to improve the image.
- This test is painless, and the dose of radiation is small and will not make you radioactive.
- A mammogram is a low-dose x-ray of the breast. The breast is positioned against an x-ray plate and gently but firmly compressed with a clear plastic plate. This test can be uncomfortable but usually only takes 10–30 minutes.
Ultrasound
- This test uses soundwaves to build up a picture of your body.
- A device is placed on or in your body. It sends out soundwaves that echo when they meet something dense, like a tumour. The images are projected onto a computer screen.
- The device may be a small, handheld device (transducer) that is passed over part of your body, such as your abdomen. It may also be a probe that is inserted into part of your body, such as the vagina or rectum.
- An ultrasound takes 10–20 minutes. While it is usually painless, it can be uncomfortable.
CT scan
- Computerised tomography scan.
- This test uses x-ray beams to produce detailed pictures of the inside of the body.
- Before the scan, you may be given a drink or an injection of a dye (called the contrast) to make the pictures clearer. The dye may make you feel hot all over for a few minutes and cause a strange taste in your mouth.
- The dye can cause allergies in some people. If you've had a reaction to dyes during a previous scan, let your medical team know.
- You lie on a table that moves in and out of the scanner, which is large and round like a doughnut. The scan can take up to 30 minutes.
PET-CT scan
- Positron emission tomography scan, combined with a CT scan.
- The PET scan uses low-dose radioactive glucose to measure cell activity in different parts of the body.
- A sample of your blood is taken and mixed with the low-dose radioactive glucose before it is reinjected into a vein. You wait 30–90 minutes for the solution to circulate through your body.
- You then have a CT scan. Cancer cells generally use more glucose than the surrounding tissue does, so any areas of cancer light up on the scan.
Bone scan
- This test shows any abnormal areas of the bones.
- A small amount of a radioactive dye is injected into a vein, usually in the arm.
- You wait 2–3 hours to allow the dye to circulate and be absorbed by your body.
- A scan of your whole body is then taken and any abnormal areas show up as highlighted areas, which are known as hot spots.
- This scan is painless and will not make you radioactive.
MRI scan
- Magnetic resonance imaging scan.
- This uses a magnet and radio waves to take detailed pictures of an area of the body.
- Dye (contrast) may be injected into a vein before the scan to make the images clearer.
- You lie on a table that slides into a narrow metal cylinder that is open at both ends. The cylinder makes some people anxious, but you can ask for a mild sedative beforehand to help you relax. The scan is also noisy, so you will probably be given earplugs or headphones to help block the sound.
- People with some types of pacemakers or other metallic objects cannot have an MRI.
Staging is a way to describe the spread of cancer. However, CUP cannot be given a stage because the primary cancer is not known and the cancer has already spread to other parts of the body when it is found.
This is considered advanced cancer. For more information, read Living with Advanced Cancer and listen to our podcast series, The Thing About Advanced Cancer.
Gary's story
"At the time of my diagnosis, I was working as a senior lawyer. One morning, I was on the phone to a client and looking out the window. I was running a hand over my chin when I felt a lump. I actually said to the client, 'I've just felt this lump, so I'm going to see my GP. Goodbye.'
"I had to have a needle biopsy the next day and the results of that were significant. It was squamous cell carcinoma and it was metastatic.
"The doctors did another couple of biopsies to look for the primary, but they couldn't find it. They guessed the cancer had started in my mouth, but I had a fair complexion and red hair, so it might also have started somewhere on my skin.
"I had surgery to take out most of my molars, then more surgery to remove all the lymph nodes down one side of my neck.
"Even though we hadn't found the primary cancer, I talked about the treatment options with my doctors and we agreed to forge ahead. I was 51 and fit, so we decided on a broad approach with a combination of strong chemotherapy and radiation therapy.
"The cancer diagnosis knocked me for six. I went into a deep black hole. The fact that it was CUP didn't affect me at the time – I actually didn't grasp what metastatic meant.
"I like to think that I'm a fairly optimistic and together person, but after the treatment was over, I struggled with anxiety about the cancer recurring. The fact that the primary cancer wasn't found added to that anxiety – it was an extra element.
"I ended up seeing a psychiatrist about a year after my treatment, but it would have been better to get that sort of help earlier."
Prognosis
Prognosis means the expected outcome of a disease. You may wish to discuss your prognosis and treatment options with your doctor, but it is not possible for anyone to predict the exact course of the disease.
To work out your prognosis, your doctor will consider test results; the type of CUP you have; where the cancer is located and how far it has spread through the body; how fast the cancer is growing; how well you respond to treatment; the impact the cancer has had on your health; and factors such as your age, fitness and medical history.
Although most cases of CUP can’t be cured, treatment can keep some cancers under control for months or years. Whatever the prognosis, palliative treatment can relieve symptoms such as pain to improve quality of life. It can be used at any stage of advanced cancer.
Discussing your prognosis and thinking about the future can be challenging and stressful. It is important to know that although the statistics for CUP can be frightening, they are an average and may not apply to your situation. Talk to your doctor about how to interpret any statistics that you come across
Get support
Many people feel shocked and upset when told they have cancer. It can be even more distressing if the cancer has spread and the original (primary) site cannot be found.
Cancer Council's experienced nurses can help you connect with other people who are living with advanced cancer, and provide you with information about the emotional and practical aspects of living with CUP.
Contact cancer support
Understanding Cancer of Unknown Primary
Download our Understanding Cancer of Unknown Primary booklet to learn more and find support.
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