CA 125 Levels: Your Guide | 1

Introduction
Women who are suspected of having ovarian cancer and
women who have been diagnosed with ovarian cancer may
receive a blood test to measure their CA 125 level.

This association between ovarian cancer and CA 125 often leads to confusion
and misunderstanding about what this test means for diagnosis of ovarian
cancer and/or its impact on the clinical management of ovarian cancer.

This booklet will take you through the basics of what you need to know about
CA 125 — what it is, what it’s measuring, and what the values mean. And
hopefully, this information will help you better understand how this test is used
and interpreted in your treatment and follow-up.

What is CA 125?
CA 125 is a substance found in the In other words, CA 125 may not
blood called a glycoprotein (a sugar- be elevated in someone who does
associated protein). It is commonly have cancer and can be elevated in
referred to as a “biomarker” — or someone who does not have cancer.
“tumor marker” — because it provides Additionally, the number itself does
information about the biological state not correlate with how much disease
of a disease (ovarian cancer) and is a person has. Two patients with the
obtained by a blood sample from same level can have a widely differently
which a level can be measured. extent of cancer. As you’ll see or have
Measurement of CA 125 is the most personally experienced, this is certainly
commonly used test to assist in the case for ovarian cancer patients.
diagnosing and following ovarian Nevertheless, as a tool, serial changes
cancer. However, it is not a perfect in CA 125 levels, if elevated, can be
test because it is only elevated in fairly representative of disease status
approximately 50% of women who and frequently very helpful in the
have early-stage ovarian cancer and assessment of women with
85% of women with advanced ovarian cancer.
ovarian cancer.

2 | Foundation for Women’s Cancer

The history of the CA 125 test
The current CA 125 blood test is the New studies were launched to see if
second generation of the test first CA 125 might be useful as a test to
introduced in the early 1980s’ as a diagnose and follow ovarian cancer
possible treatment. Based on early patients. Eventually, a CA 125 level of
experience with immune therapy for 35 units was found to be a useful cutoff
cancer, investigators started searching point, with 99% of healthy women
for something unique on the surfaces having values less than 35. Levels
of ovarian cancer cells that could above 35 units are certainly seen in
be used to trigger recognition of healthy women, but beyond the cutoff
tumor cells by the immune system. point of 35, the higher the value, the
After 125 attempts, an antibody was more likely there is trouble somewhere
found that seemed to do the trick. in the body. Women with ovarian
The antibody was termed OC-125 cancer often have levels measured in
(for the 125th antibody tested against hundreds and even thousands of units.
ovarian cancer cells) and recognized
a tumor cell surface signal termed So, the CA 125 test is helpful, but not
CA 125. Unfortunately, attempts to perfect. Individual values are hard to
use this antibody in treatment were interpret, so many physicians focus
not successful. However, creative on the trend in values over a course
researchers recognized an interesting of time rather than on any individual
phenomenon about the protein and value. Time trends help to put the
antibody they were testing — the levels individual values into perspective to
in the blood seemed to correlate with get a “picture” of what might be going
the status of the ovarian cancer. on in a particular situation.

CA 125 Levels: Your Guide | 3

CA 125 and false elevation
Normal tissues, including ovarian, pancreatic, and breast
cells, and the lining tissue of the abdomen and chest all
make and release low levels of CA 125. Since the CA 125
test reflects the amount of protein (often called antigen)
released into the bloodstream from specific organs,
conditions that cause irritation or inflammation can change
the test result. Ovarian cancer not only increases the
number of cells that make CA 125, but also perturbs or
inflames the abdominal lining, which contains “normal” cells
that make and release CA 125. So, it’s not surprising that
CA 125 is elevated in ovarian cancer and in some other
cancers in the abdomen.

But other, noncancerous conditions can elevate the CA 125

value, such as inflammatory conditions of the abdomen
(diverticulitis, peritonitis, pelvic inflammatory disease,
inflammatory bowel disease, tuberculosis, and pancreatitis),
cardiac conditions such as congestive heart failure, liver
disease, recent surgery, and benign gynecologic conditions
such as fibroids, endometriosis, ectopic pregnancy, or a
ruptured cyst. In some situations, CA 125 is even used
to monitor the effects of treatment for benign conditions
such as endometriosis. These other diagnoses must be
considered in the interpretation of an elevated CA 125 value.

4 | Foundation for Women’s Cancer

Potential applications
of the CA 125 test
The CA 125 test is used in a variety of situations during the
course of diagnosis, treatment, and follow-up of ovarian and
other closely related cancers, such as primary peritoneal and
fallopian tube cancers.

Five primary roles for CA 125 assessment have been established, with varying
degrees of clinical use and reliability. The five major roles are:

Outcome prediction: CA 125 has Monitoring: CA 125 is used

been studied for its ability to predict throughout the course of
treatment outcome in women with chemotherapy to monitor or
ovarian cancer and closely related assess treatment effectiveness.
cancers, such as fallopian tube and
primary peritoneal cancer. Screening: CA 125 is often used to
screen for ovarian, primary peritoneal,
Detection: CA 125 is widely used and fallopian tube cancers in high-risk
to detect recurrent ovarian cancer women or in women with abnormal
in women who have been findings on examination or ultrasound.
previously treated.
Pelvic mass triage: CA 125 is
included as a marker to help determine
the risk of a malignancy preoperatively.

CA 125 Levels: Your Guide | 5

Outcome prediction Recurrent disease detection
While more research is needed to The CA 125 test is most reliable and
completely determine how well a CA useful for the detection of recurrent
125 test can predict the outcome disease in women previously
of cancer treatment, several recent diagnosed with and treated for ovarian
studies have looked at this question. cancer. Also, CA 125 levels can be
If, during the first time a woman is elevated even when an exam and scan
treated for ovarian cancer, her CA 125 (CT or PET) do not show any cancer.
level returns to “normal,” will she have a This is called “biochemical recurrence.”
better chance of survival? The role of the CA 125 test results and
when to start treatment for recurrent
The answer seems to be “yes,” but disease should be discussed with your
with a note of caution. This conclusion gynecologic oncologist.
only seems to be true when looking at
the trends for large groups of women. While there are certainly exceptions,
CA 125 levels do not work as well as a generally, rising numbers over a
predictor for individual women. series of tests strongly suggest that a
woman is experiencing a recurrence of
her disease. However, some women
develop a recurrence without a rising
CA 125 level. On the other hand, some
women have a modest rise in the value
but never develop recurrent disease.

Recent evidence has suggested that

using CA 125 to diagnose recurrent
disease sooner does not result in an
overall improved survival. Furthermore,
following these values more closely
caused physicians to administer more
chemotherapy, thus worsening quality
of life without improving outcomes.
The role of CA 125 in the setting of
detecting recurrent disease should be
discussed with your doctor.

6 | Foundation for Women’s Cancer

Treatment monitoring
The CA 125 test is a generally reliable Monitoring changes in the CA 125
tool to use along with a thorough value while on treatment can provide
history and physical exam to assess some of the earliest clues that
or monitor if a treatment is working. your therapy is working. However,
However, its usefulness depends it’s important not to over interpret
on the starting value. Monitoring is the values. For instance, some
most accurate when patients have an chemotherapy and biologic agents
elevated initial CA 125 value. Some used in recurrent disease treatment,
information is emerging suggesting such as pegylated liposomal
that the trends in CA 125 values within doxorubicin (Doxil) and topotecan
what is generally considered the (Hycamtin), require closer scrutiny
normal range may also provide clues to as a significant number of patients
treatment success. may have a rise in their CA 125
values — as much as 30%— after
It is vital to stress that this test their first cycle of chemotherapy,
represents just a piece of the puzzle, and yet go on to respond to these
and a number of other factors are drugs upon continued administration.
considered in determining whether Some patients even have a rise in CA
any given therapy is working to fight 125 after their second or third cycle
the cancer. It is also important to and still had a favorable treatment
emphasize that CA 125 values may outcome. Similarly, bevacizumab, a
go up or down for a variety of reasons targeted biologic agent, may cause
and, because of this, the test may not elevated CA 125 values despite having
accurately reflect disease status. This a positive treatment effect. So, CA 125
is particularly true when the values values can and do fluctuate. Major
are in the normal range or are only treatment decisions, such as changing
minimally elevated. Most clinicians rely or discontinuing treatment, depend
on how the numbers change over time on multiple factors that you and your
and not on one test result alone. physician will consider. The trend in
your CA 125 values is only one of
these factors.

CA 125 Levels: Your Guide | 7

Ovarian cancer screening
As is the case with most cancers, early However, researchers continue to
detection of ovarian cancers leads to look into other possibilities for ovarian
a higher cure rate. Because there is cancer screening. One option that
not yet a highly effective screening test seems to hold promise is the use
for ovarian cancer, and the symptoms of several tests, including the CA
of this cancer are variable, many 125 test, performed in sequence or
women are diagnosed at a later, less together as indicators of the presence
treatable stage. Therefore, much effort of ovarian cancer. Some recent
is directed toward being able to screen research has shown promise using
for this cancer, or at least detect it at the CA 125 test over time to look for
its earliest and most treatable stage. changes within an individual patient
followed by ultrasound in those with
The CA 125 test alone has proven to elevated values. But it is too early
be ineffective in screening for ovarian to know if this approach will prove
cancer in the general population. beneficial for the general population in
In fact, one recent study of women terms of cost and lives saved.
receiving an annual CA 125 and
an ultrasound led to an increase Pelvic mass triage
in adverse outcomes compared
CA 125 has been used as part of a
to women who did not undergo
panel of biomarkers to determine the
screening because the abnormal
likelihood that a mass on imaging
test results led to unnecessary
or exam is malignant. CA 125 is one
surgical procedures. As explained
of several markers in multianalyte
earlier, many factors influence “the
platforms. These tests estimate the
number,” making it unreliable as a
risk of a malignancy preoperatively to
screening test for ovarian or any other
allow proper triage of a patient to a
reproductive cancer. The test misses
gynecologic oncologist in the event of
up to 50% of early ovarian cancers,
an elevated risk score.
when treatment is most successful.
Furthermore, the test is falsely elevated
in a portion of the population due to
conditions unrelated to cancer. CA
125 is especially unreliable in screening
premenopausal women because both
ovulation and menstruation can cause
elevated levels.

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Recent FDA statement
In September 2016 the U.S. Food & Drug Administration
(FDA) issued a safety communication that recommends
against using tests that are currently marketed for ovarian
cancer screening. According to the statement, “The
Agency is especially concerned about delaying effective
preventive treatments for women who show no symptoms,
but who are still at increased risk for developing ovarian
cancer. Based on currently available information, the FDA
recommends against using currently offered tests to screen
for ovarian cancer.”

The FDA made the following recommendations regarding

ovarian cancer screening tests for women, including those
at increased risk of developing ovarian cancer:

• Be aware that there is currently no safe and effective

ovarian cancer screening test.

• Do not rely on ovarian cancer screening test results to

make health or treatment decisions.

• Talk to your doctor about ways to reduce your risk of

developing ovarian cancer, especially if you have a family
history of ovarian cancer, or have the BRCA1 or BRCA2
genetic mutations.

CA 125 Levels: Your Guide | 9

Future interventions
Many novel applications for CA 125 are emerging including using this test to
assess response to neoadjuvant chemotherapy and predict the ability of the
surgeon to cytoreduce. Additionally, CA 125 can be used in dynamic modeling to
assess the efficacy of drugs in early development.

A final note
We urge women diagnosed with ovarian cancer to keep in mind that the CA 125 test
is only one indication of how well the treatment is working. Gynecologic oncologists,
who are obstetrician-gynecologists with an additional three to four years of training
in the comprehensive treatment of women with gynecologic cancers, are specifically
knowledgeable about how to interpret a CA 125 test result in the treatment of
ovarian cancer.

For information on how to find a gynecologic oncologist and general

information about ovarian and other women’s cancers, please visit
foundationforwomenscancer.org.

For more information on ovarian and other gynecologic cancers, please call or
e-mail the Foundation for Women’s Cancer at 312-578-1439 or
[email protected].

10 | Foundation for Women’s Cancer

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 The Foundation for Women’s Cancer (FWC) is a 501(c)3 nonprofit
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gynecologic cancer risk, prevention, early detection and optimal treatment.

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