Diagnosing unknown primary cancer

Sunday 1 May, 2016

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On this page: Blood and urine tests | Biopsy | Endoscopy | Imaging tests | Prognosis | Gary's story | Key points

Before CUP is diagnosed, you will usually see your GP, who will examine you, send you for tests and refer you to a specialist doctor. The specialist will ask you about your general health and any previous medical problems.

This section describes the various tests that your doctors may arrange. Initially, the purpose of the tests is to work out whether you have cancer, and whether it is primary or secondary. If the tests show that the cancer is secondary, you will have further tests to try to find the primary cancer.

The recommended tests for CUP vary depending on your general health, the location of the secondary cancer and the presumed location of the primary cancer. Often several different tests are needed to look for the primary cancer. You may have questions about the tests your doctor suggests – see our Question Checklist.

Blood and urine tests

These tests will look for abnormal cells and measure the levels of certain chemicals (tumour markers).


In this procedure, samples of tissue are removed from a secondary tumour or an enlarged lymph gland and sent to a laboratory for examination under a microscope.


This procedure uses an instrument called an endoscope to look inside the body and remove small tissue samples.

Imaging tests

X-rays, ultrasounds and CT, PET-CT, MRI and bone scans create images of the inside of the body.

If these tests find where the cancer started, the cancer is no longer an unknown primary and is treated like the primary cancer type.

Blood and urine tests

A complete blood count checks the levels of red blood cells, white blood cells and platelets. Urine may also be tested for any abnormal cells or substances and to see if there are any problems with organs such as the kidneys or bladder.

Tumour markers are chemicals made by some cancer cells. Some are found in the blood, but others are found in urine or other body fluids. Your symptoms and sex help the doctor decide if it would be helpful to check for any of these markers. Tumour markers include:

  • prostate specific antigen (PSA) – high PSA levels may indicate prostate cancer
  • alpha-fetoprotein (AFP) – high AFP levels may be a sign of testicular or liver cancer
  • human chorionic gonadotropin (HCG) – high levels of HCG can suggest testicular cancer or a rare type of ovarian cancer
  • carcinoembryonic antigen (CEA) – CEA levels may be raised in people who have bowel cancer. Other cancers that may have high CEA levels include lung, pancreatic, stomach, ovarian, breast, thyroid and liver cancers
  • cancer antigen 125 (CA125) – CA125 levels may be raised in women with ovarian cancer.


A biopsy is the removal of a tissue sample for examination in a laboratory. It is usually the most important test in the diagnosis of CUP because it can show what type of cell has changed, and this indicates where in the body the cancer may have started.

The tissue sample is often removed under local anaesthetic, but it may sometimes be removed under general anaesthetic. You may have one of the following types of procedures:

  • fine needle aspiration – removes cells using a thin needle
  • core biopsy – removes tissue using a wide needle
  • incisional biopsy – cuts out only part of a tumour
  • excisional biopsy – cuts out the whole tumour.

At the laboratory, a specialist doctor called a pathologist will run a series of stains on the sample to see if they can work out the type of cancer. These stains may show specific changes in the cells or highlight proteins (antigens) that are linked to various types of cancer. It may be a week or more before results are available.

Some labs can test a biopsy for genetic changes or patterns linked to specific types of cancer. These may be called cytogenetic tests or gene expression-based profiling (GeBP). As it is not yet clear how useful these tests are, their availability is still limited.

A biopsy may not be helpful if the cancer is too difficult to reach or if you’re too unwell for the procedure. Talk to your doctor if you have any questions about this.


This procedure is used to look inside the body for any abnormal areas. A thin, flexible tube with a light and camera on the end, called an endoscope, is inserted through a natural opening (such as the mouth, anus or vagina) or through a small cut made by the surgeon. The endoscope has a small cutting instrument on the end so a biopsy can be taken at the same time if something suspicious is seen. The most common types of endoscopies are listed in the table below.

Type of endoscopy
 Part of the body tested
Where the tube is inserted
lungs or respiratory tract  mouth or nose
colon (large bowel)
vagina and cervix
 organs are viewed from outside the vagina
bladder  urethra
stomach and small bowel
uterus (womb)
stomach, liver, female reproductive organs
 small cuts in the abdomen
larynx (voice box)
colon (large bowel)
lungs  small cut in the chest

Imaging tests

  • This test creates pictures of the inside of the body.
  • X-rays of the chest and other parts of the body may be taken.
  • 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.
  • This test uses soundwaves to build up a picture of your body.
  • A device is placed on or in your body and 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, or a probe that is inserted into part of your body, such as the vagina or rectum.
  • This scan takes 10–20 minutes and should be painless.
CT scan
  • Computerised tomography scan.
  • This test uses a series of x-rays 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 particular areas easier to see. If the contrast is injected, you may feel hot all over for a few minutes and have a strange taste in your mouth.
  • The CT scanner is large and round like a doughnut. You lie on a table that moves in and out of the scanner.
  • The scan can take up to 30 minutes.
PET-CT scan
  • Positron emission tomography scan, combined with a CT scan.
  • This uses low-dose radioactive glucose to measure cell activity in different parts of the body.
  • A small amount of glucose is injected into a vein. You wait 30–90 minutes for the solution to circulate through your body.
  • Your body is then scanned. Areas of cancer usually absorb more glucose than the surrounding tissue does, so they show 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 very noisy, so you will probably be given earplugs or headphones to help block the sound.


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 any doctor to predict the exact course of your disease.

To come up with your prognosis, your doctor will consider test results, the type of CUP you have, the rate and depth of tumour growth, how well you respond to treatment, and other factors such as your age, fitness and medical history.

Although most cancers of unknown primary can’t be cured, treatment can keep some cancers under control for months or years. For example, some people with a localised deposit of CUP (e.g. in a lymph node in the neck) are able to achieve long-term control, or sometimes even a cure, with surgery or high-dose chemoradiation (a combination of chemotherapy and radiotherapy).

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.

"I’ve been having palliative treatment for five years. I’m not trying to get rid of the disease, just keeping it under control. My quality of life is excellent." - Kate

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 radiotherapy.

"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 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." 

Key points

  • Several different tests are used to try to identify the primary cancer.
  • The type of tests you have will depend on your general health, the location of the secondary cancer, and the presumed location of the primary cancer.
  • Blood tests will examine the number and type of blood cells and will measure the levels of various blood chemicals (tumour markers). Urine may also be tested to check for abnormal cells.
  • Taking a tissue sample (biopsy) is the main test for CUP. There are a few ways of doing a biopsy. The doctor may use a needle to take out the tissue (fine needle aspiration or core biopsy). Other options involve surgically removing the sample (incisional or excisional biopsy).
  • An endoscopy is another way to look inside the body and remove small tissue samples. This procedure uses a thin, flexible tube called an endoscope. Different types of endoscopies are known by different names, e.g. a colonoscopy checks the colon (large bowel).
  • Imaging scans such as x-rays, ultrasounds, MRI, CT, PET-CT and bone scans may be used to create pictures of the inside of the body.
  • If any of these tests find where the cancer started, the cancer is no longer an unknown primary and is treated according to the primary cancer type.
  • Your doctor may talk to you about your prognosis. This is a general prediction about what may happen to you, but no-one can predict the exact course of your illness.

Reviewed by: A/Prof Linda Mileshkin, Medical Oncologist, Peter MacCallum Cancer Centre, VIC; Dr Sarwan Bishnoi, Medical Oncologist, Adelaide Cancer Centre, SA; Dave Clark, Consumer; Dr Jan Maree Davis, Area Director, Palliative Care Service, Calvary Health Care and St George Hospital, NSW; Linda Tompsitt, Cancer Nurse 13 11 20, Cancer Council WA; Catherine Trevaskis, Gastrointestinal Cancer Specialist Nurse, The Canberra Hospital, ACT.

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