Raised Tumour Markers: What Does It Mean?

A raised tumour marker is not a diagnosis of cancer.

Markers such as CEA, CA 19-9, CA-125 and AFP can rise in some cancers, but they also rise in many conditions that are not cancer. And in some cancers tumour markers can be entirely normal.

For this reason tumour markers should not be treated on their own as a “cancer yes/no test”.

What is a tumour marker?

Tumour markers are substances whose amount in the blood can rise, either because some cancer cells produce them or as part of the body’s response to a disease.

One of the important uses of these tests is to help follow how some diagnosed cancers respond to treatment and how the disease is progressing. In certain particular situations they also contribute to diagnostic assessment.

But most tumour markers are not suitable on their own for general cancer screening in someone with no symptoms.

What does a raised CEA mean?

CEA (carcinoembryonic antigen) is a tumour marker associated particularly with colorectal cancers. But it can rise in other cancers and in conditions that are not cancer.

CEA can rise in:

• Cancer of the colon and rectum
• Stomach cancer
• Pancreatic cancer
• Lung cancer
• Breast cancer
• Some other cancers

But a raised CEA does not on its own show that any of these is present.

Can smoking raise CEA?

Yes. CEA levels can be higher in people who smoke than in those who do not.

A raised CEA can also be seen in non-cancerous conditions such as some liver diseases, inflammatory conditions, diseases of the pancreas and conditions of the bowel.

So smoking and any accompanying conditions have to be taken into account when a CEA result is being interpreted.

Is a colonoscopy needed if CEA is high?

A colonoscopy is not done for everyone on the basis of a raised CEA alone. Whether one is needed is decided by weighing factors such as:

• Age
• Blood in the stool
• Iron deficiency anaemia
• A change in bowel habit
• Weight loss
• Family history
• A previous history of polyps
• Where the person stands with bowel cancer screening

CEA is not a bowel cancer screening test that takes the place of colonoscopy.

What does a raised CA 19-9 mean?

CA 19-9 is a tumour marker associated particularly with conditions of the pancreas and bile ducts. It can rise in some pancreatic cancers, in bile duct cancers and in some other cancers of the stomach and gastrointestinal tract. But:

A raised CA 19-9 does not mean pancreatic cancer.

Can CA 19-9 rise without cancer?

Yes. This is a particularly important point. CA 19-9 can also rise in harmless conditions such as:

• Blockage of the bile ducts
• Infection of the bile ducts (cholangitis)
• Gallstone disease
• Pancreatitis
• Some liver diseases

When the bile ducts are blocked in particular, CA 19-9 can sometimes rise markedly. The value can fall again once the blockage is relieved.

For this reason bilirubin, ALP, GGT and imaging findings matter a great deal when a CA 19-9 result is being assessed.

If CA 19-9 is normal, is there no pancreatic cancer?

No. A normal CA 19-9 does not definitively rule out pancreatic cancer. In addition, a small proportion of people cannot produce CA 19-9 in sufficient amounts for genetic reasons.

So:

• A high CA 19-9 → does not on its own make a diagnosis of cancer.
• A normal CA 19-9 → does not definitively rule cancer out.

What does a raised CA-125 mean?

CA-125 is most often associated with ovarian cancer, but it is not a marker specific to cancer alone.

It also matters in gastroenterology, because it can rise in some conditions where the peritoneum is affected and fluid collects in the abdomen.

Can CA-125 rise without cancer?

Yes. CA-125 can also rise in non-cancerous situations such as:

• Menstruation
• Endometriosis
• Pregnancy
• Pelvic inflammatory conditions
• Liver disease
• Cirrhosis
• Fluid in the abdomen (ascites)
• Some conditions affecting the peritoneum

A raised CA-125 can be seen particularly in patients with cirrhosis and ascites, and this does not on its own mean cancer.

CA-125 is high — is it ovarian cancer?

No. CA-125 does not on its own make a diagnosis of ovarian cancer.

Where needed, the result is weighed together with gynaecological assessment, ultrasound, other imaging, the patient’s age and menopausal status, and the clinical findings.

What does a raised AFP mean?

AFP (alpha-fetoprotein) is an important marker encountered in adults particularly in assessing liver disease.

AFP can rise in some hepatocellular carcinomas (primary liver cancer) and in germ cell tumours. But a raised AFP is not on its own a diagnosis of cancer either.

Can AFP rise in liver disease without cancer?

Yes. AFP can rise in some active liver diseases and in situations where the renewal of liver cells is increased. A rise in AFP can be seen, for example, in some acute hepatitis, in chronic hepatitis and in cirrhosis.

For this reason an AFP result has to be weighed together with liver tests and imaging findings.

Does AFP rise in pregnancy?

Yes. AFP is a protein naturally produced in fetal life. So AFP levels in a mother’s blood during pregnancy are assessed differently.

An AFP measurement taken during pregnancy is not interpreted in the same way as one taken in an adult to assess liver disease.

The higher the value, the more likely cancer is?

It is not that simple.

How far the marker has risen, which marker it is and the patient’s clinical situation all matter. Mild rises can quite often have causes that are not cancer. In some situations a marked rise calls for more investigation.

But for no tumour marker can it be said, from the number alone, “this value is high, therefore it is certainly cancer.”

Which matters more — a single measurement or the change?

Particularly in following a diagnosed condition, the change in a tumour marker over time can be more meaningful than a single value. For example:

• 35 → 38 → 36
• 35 → 90 → 250

are not the same. But a rising trend does not on its own make a diagnosis of cancer either; its cause needs looking into.

My marker is high — should I have a PET-CT straight away?

Usually not.

Going straight to a PET-CT because of a single raised tumour marker is not an appropriate approach. First the following are assessed:

• Why the test was requested
• The patient’s symptoms
• The examination findings
• Other laboratory results
• Previous results
• Age and risk factors

From that it is decided which of ultrasound, CT, MRI, endoscopy, colonoscopy, EUS or another investigation is needed.

If I have all four markers done, is that cancer screening?

No.

CEA, CA 19-9, CA-125 and AFP all coming back normal does not mean “there is no cancer in the body”. Equally, one of them coming back high does not mean “there is cancer”.

Broad panels of tumour markers do not take the place of general cancer screening in healthy people. Cancer screening should be done by methods appropriate to a person’s age and risks and shown to be effective.

What is done when a tumour marker comes back high?

First it should be known why the test was requested. Your doctor will weigh together:

• How high the result is
• Previous results
• Whether the rise is persistent
• The patient’s symptoms
• Smoking
• Liver and bile duct tests
• Their other conditions
• The medicines they take
• Imaging results

If needed, the marker may be measured again or appropriate imaging or endoscopic investigation planned.

Which marker relates to what, briefly?

Marker	Often associated with	Examples of non-cancer rises
CEA	Colorectal cancer in particular, and some other cancers	Smoking, inflammation, some liver and gastrointestinal conditions
CA 19-9	Cancers of the pancreas and bile ducts	Blocked bile ducts, cholangitis, pancreatitis, liver disease
CA-125	Ovarian cancer in particular, peritoneal conditions	Menstruation, endometriosis, pregnancy, cirrhosis and ascites
AFP	Hepatocellular carcinoma, some germ cell tumours	Pregnancy, hepatitis and some chronic liver diseases

Which symptoms mean assessment should not be delayed?

It matters that the cause be looked into if a raised tumour marker is accompanied by:

• Unexplained weight loss
• Blood in the stool or black stools
• New jaundice
• Increasing swelling of the abdomen
• Marked loss of appetite or early fullness
• Abdominal pain that does not pass or keeps worsening
• Unexplained iron deficiency anaemia
• A lasting change in bowel habit

What should you do if your marker is high?

1. Do not panic. A raised tumour marker is not a diagnosis of cancer.
2. But do not ignore the result either. The cause of the rise should be weighed together with the clinical picture.
3. Find your previous results. The change over time can give useful information.
4. Find out why the test was requested. Screening, helping with a diagnosis and following a known cancer are different purposes.
5. Weigh it with your other investigations. A diagnosis is not made from a single tumour marker.
6. Do not arrange imaging for yourself. Which investigation is needed should be decided after clinical assessment.

Remember

• A high CEA Does not on its own mean bowel cancer.
• A high CA 19-9 Does not on its own mean pancreatic cancer; it can rise with a blocked bile duct too.
• A high CA-125 Does not on its own mean ovarian cancer; it can rise in cirrhosis and ascites too.
• A high AFP Does not on its own mean liver cancer.
• A raised tumour marker Is not a diagnosis but a laboratory finding to be looked into where needed.
• Normal markers Do not definitively rule cancer out.