Diagnosing unknown primary cancer

Thursday 1 May, 2014

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On this page: Blood tests | Urine testsBiopsyEndoscopyImaging tests | Which health professionals will I see? | Prognosis | Key points

Usually you begin by seeing your general practitioner (GP). They will examine you, send you for tests and refer you to a specialist. The specialist will ask about your general health and any previous medical problems.

The recommended diagnostic tests for CUP vary depending on your general health, the location of the secondary cancer and the presumed location of the primary cancer. This chapter describes the tests you may have. Often several different tests are needed to look for the primary cancer. You may have questions about the tests your doctor suggests. 

  • Blood tests – These will examine the number and type of blood cells and measure the levels of certain blood chemicals (tumour markers).
  • Biopsy – Samples of tissue from a secondary tumour or an enlarged lymph gland are removed for examination under a microscope.
  • Endoscopy – A procedure that uses an instrument called an endoscope to look inside the body and remove small tissue samples.
  • Imaging tests – X-rays, ultrasounds and CT, MRI and PET scans create pictures 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 according to the tissue of origin.

Blood tests

A complete blood count checks the levels of red blood cells, white blood cells and platelets.

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 which markers to check. These may include:

  • prostate specific antigen (PSA) – a high PSA level may indicate prostate cancer
  • alpha-fetoprotein (AFP) – high levels may be a sign of testicular or liver cancer
  • human chorionic gonadotrophin (HCG) – high levels of HCG can suggest cancer of the placenta (inside the uterus) or a rare type of ovarian cancer
  • carcinoembryonic antigen (CEA) – may be raised in people who have bowel cancer. Other cancers that may have a high CEA level include lung, pancreatic, stomach, ovarian, breast, thyroid and liver
  • cancer antigen 125 (CA 125) – may be raised in women with ovarian cancer
  • cancer antigen 19-9 (CA 19-9) – may be raised in people with stomach, liver or pancreatic cancer.

Urine tests

Urine can be tested for any abnormal cells or substances and to see if there are any problems with organs such as the kidneys or bladder.


This provides information about the type of cell the cancer developed from. A tissue sample may be removed with a general anaesthetic but it is often done under local anaesthetic.

You may have one of the following types of biopsies: 

  • Fine-needle aspiration – removes cells using a thin needle
  • Core – removes tissue using a wide needle
  • Excisional – surgically removes an entire piece of tissue.

The following lab tests of the biopy samples may be conducted:

  • Immunohistochemistry – uses dyes to find particular proteins called antigens in cells of a tissue section
  • Histology study – a stain is added to a sample of cancer cells and viewed under a microscope to look for specific changes.
If the cancer is too difficult to reach or if you’re too unwell for the procedure, you may not benefit from having a biopsy. Talk to your doctor about this.


This procedure is used to look inside the body for any abnormal areas. A thin, flexible tube with a camera on the end, called an endoscope, is inserted through one of the body’s natural openings, such as the mouth, anus or vagina. 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.

Imaging tests

Bone scan
  • This shows any abnormal areas of the bones.
  • A small amount of a radioactive dye is injected into a vein, usually in the arm.
  • You will 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, known as hot spots.
  • This scan is painless and will not make you radioactive.
  • This 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 is used to improve the detail of the image.
  • This test is painless and the dose of radiation is small and will not make you radioactive.
  • A low-dose x-ray of the breast.
  • The breast is positioned against an x-ray plate and gently but firmly compressed with a flat, clear, plastic plate.
  • This test can be uncomfortable but only lasts for a short time.
CT scan
  • Computerised tomography scan.
  • It uses a series of x-rays to produce detailed pictures of the inside of the body.
  • The scan can take up to 30 minutes.
  • Before the scan, you may be given a drink or an injection of a dye to make particular areas easier to see. This may make you feel hot all over for a few minutes and leave a strange taste in your mouth.
  • The CT scanner is large and round like a doughnut. You will lie on a table that moves in and out of the scanner.
MRI scan
  • Magnetic resonance imaging scan.
  • It uses a magnet and radio waves to take detailed pictures of an area of the body.
  • Dye may be injected into a vein before the scan to help make the pictures clearer.
  • You will lie on a table that slides into a narrow metal cylinder that is open at both ends. Lying in the cylinder makes some people feel anxious, but they can have a mild sedative to relax them.
  • People with a pacemaker or other metallic object in their body cannot have an MRI.
PET (positron emission tomography) scan
  • Positron emission tomography scan.
  • It 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 will wait for 30–90 minutes for the solution to circulate through your body.
  • Your body is then scanned. Areas of cancer usually absorb more sugar than surrounding tissue and show up on the scan.
  • It is usually done on an outpatient basis.

Which health professionals will I see?

The specialist you see will depend on the symptoms you have and the presumed location of the primary cancer. A few hospitals have dedicated CUP clinics.

It is common for people diagnosed with cancer to be cared for by a range of health professionals who specialise in different aspects of their treatment. This is called a multidisciplinary team. 

Health professional Role
gastroenterologist digestive tract, bowel or stomach symptoms
gynaecologist symptoms of the vagina, cervix, uterus or ovaries (female reproductive system), and sees women who have fluid collecting in the abdomen (ascites)
respiratory physician or thoracic surgeon
chest/lung symptoms
symptoms to do with your blood cells
urinary or kidney symptoms; disorders of the male reproductive system
medical oncologist prescribes and coordinates chemotherapy
radiation oncologist
prescribes and coordinates radiotherapy
radiation therapist
administers radiotherapy
surgically removes tumours
nurses administer drugs and support you and your family through all stages of your treatment and recovery
cancer care coordinator
supports patients and families throughout treatment and liaises with other staff
palliative care doctors and nurses
work closely with the GP and oncologist to provide palliative care
recommends an eating plan to follow while you are in treatment and recovery
occupational therapist, physiotherapist
rehabilitate patients with physical side effects
social worker, psychologist
link you to support services and help with emotional, physical or practical issues
pastoral care worker
 talks about any spiritual matters


Prognosis means the expected outcome of a disease. The doctor most familiar with your situation is the best person to discuss your prognosis with, but it is not possible for any doctor to predict the exact course of the disease.

Although most cancers of unknown primary can’t be cured, treatment can keep some cancers of unknown primary under control for months or years. Some people with localised disease in the neck can achieve long-term control of the disease with surgery or high-dose chemoradiation. In other cases, palliative treatment can relieve symptoms such as pain and help to improve quality of life. See treatment for more information.

Asking questions about prognosis is a personal decision. It is up to you to decide how much information you want.

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).
  • Taking a tissue sample (biopsy) is the most important test. There are a few ways of doing a biopsy. The doctor will use a needle to take out the tissue.
  • Another way to look inside the body and remove small tissue samples is with an endoscopy. This uses an instrument called an endoscope.
  • Imaging scans such as x-rays, ultrasounds, CT, MRI and PET scans may be used to create pictures 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 according to the tissue of origin.
  • You may see many different health professionals who will work together as a multidisciplinary team to diagnose and treat you.
  • Your doctor may talk to you about your prognosis. This is a general prediction about what may happen to you. No one can predict the exact course of your illness. 

Reviewed by: A/Prof Linda Mileshkin, Consultant Medical Oncologist, Division of Cancer Medicine, Peter MacCallum Cancer Centre, VIC; Karen Hall, Nurse Counsellor, Helpline, Cancer Council SA and Clinical Nurse, Oncology/Haematology Inpatient Unit, Flinders Medical Centre, SA; A/Prof Chris Karapetis, Director of Clinical Research, Medical Oncologist, Flinders Centre for Innovation in Cancer, SA; A/Prof Claire Vajdic, Team Leader, Cancer Aetiology and Prevention Group, Prince of Wales Clinical School, Lowy Cancer Research Centre, University of NSW, NSW; and Robyn Wagner, Consumer.

Updated: 01 May, 2014