Diagnosing unknown primary cancer
On this page: Blood tests | Urine tests | Biopsy | Endoscopy | Imaging 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
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
- Biopsy – Samples of tissue from a secondary tumour or an
enlarged lymph gland are removed for examination under a
- 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.
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 can be tested for any abnormal cells or substances and
to see if there are any problems with organs such as the kidneys
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.
- This shows any
abnormal areas of
- 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
- This scan is painless
and will not make you
- 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
- This test is painless and
the dose of radiation is
small and will not make
- A low-dose x-ray of
- 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.
- It uses a series of x-rays
to produce detailed
pictures of the inside of
- 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.
- Magnetic resonance
- 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
- 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
- People with a pacemaker
or other metallic object
in their body cannot have
PET (positron emission tomography) scan
- Positron emission
- It uses low-dose
to measure cell activity
in different parts of
- 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
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.
||digestive tract, bowel or stomach symptoms
||symptoms of the vagina, cervix, uterus or ovaries
(female reproductive system), and sees women
who have fluid collecting in the abdomen (ascites)
or thoracic surgeon
|symptoms to do with your blood cells
|urinary or kidney symptoms; disorders of the
male reproductive system
||prescribes and coordinates chemotherapy
|prescribes and coordinates radiotherapy
|surgically removes tumours
||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.
- Several different tests are
used to try to identify the
- The type of tests you have
will depend on your general
health, the location of the
secondary cancer and the
presumed location of the
- 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
- Another way to look inside
the body and remove small
tissue samples is with an
endoscopy. This uses
an instrument called an
- 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.