What is CA-125? Questions About Ovarian Cancer Screening

CA-125 is a biomarker for ovarian cancer that is often elevated in the blood of people with ovarian cancer. It is important to understand that while the CA-125 blood test is useful when diagnosing and monitoring people with ovarian cancer, a CA-125 test alone is not an accurate diagnostic tool. Unfortunately, no single, reliable diagnostic tool exists to detect and diagnose ovarian cancer. We’re trying to change that here at Ovarian Cancer Research Alliance — and save more lives — by investing in research to find a diagnostic biomarker, and funding innovative projects that will lead to more effective prevention, treatments, and ultimately a cure.

What is the CA-125 Blood Test?

CA-125, which stands for “Cancer Antigen 125” is a protein that may be found in high amounts in the blood of patients with ovarian cancer. CA-125 is produced on the surface of cells and is released in the bloodstream. This protein is elevated in more than 80 percent of women with advanced ovarian cancers, and in 50 percent of those with early-stage cancers.

The CA-125 test is among the blood tests that may be ordered by a doctor if ovarian cancer is suspected.

Because CA-125 misses half of early cancers and can be elevated by benign conditions, such as diverticulitis, endometriosis, liver cirrhosis, pregnancy, and uterine fibroids, it is not used by itself to diagnose the disease, and the National Cancer Institute and the United States Preventive Services Task Force do not endorse using it to screen women for ovarian cancer who are at ordinary risk or in the general population. Research on new ways to use CA-125 to more accurately identify ovarian cancer is underway.

CA-125, however, is approved by the Food and Drug Administration to monitor the effectiveness of treatment for ovarian cancer and for detecting disease recurrence after treatment.

How is the CA-125 test used?

Doctors frequently order a CA-125 test when they are concerned that a woman may have ovarian cancer. Because CA-125 levels can fluctuate in response to treatment, the test is also used to monitor how well treatment is working or if alternative treatment should be considered. CA-125 (along with CT scans) is also frequently used to monitor for recurrence, though recent evidence shows that there is no clinical benefit to doing so. More on this issue here.

Can CA-125 be used to screen asymptomatic, average-risk women for ovarian cancer?

While it is sometimes used that way, there is no evidence to suggest that doing so is beneficial. The CA-125 test is most accurate in postmenopausal women with a pelvic mass. It is also important to note that in about 20 percent of cases of advanced stage disease, and 50 percent of cases of early stage disease, CA-125 is NOT elevated, even though there is ovarian cancer present — and CA-125 can also be elevated by benign conditions. For these reasons, the National Cancer Institute and the United States Preventive Services Task Force do not endorse using it to screen women for ovarian cancer who are at ordinary risk or in the general population.

Does a high CA-125 always mean cancer?

No, a high CA-125 does not always mean cancer is present. Generally speaking, the normal range of CA-125 is considered to be 0-35 units/mL, while a level above 35 units/mL is considered to be a high CA-125 level. Although a CA-125 blood test can be a useful tool for the diagnosis of ovarian cancer, it is not uncommon for a CA-125 count to be elevated in premenopausal women due to benign conditions unrelated to ovarian cancer, such as diverticulitis, endometriosis, liver cirrhosis, pregnancy, and uterine fibroids, as Medscape details here. As a result, the CA-125 is generally only one of several tools used to diagnose ovarian cancer in a patient with a pelvic mass or other suspicious clinical findings.

Are there any methods of early detection, or ways to screen for ovarian cancer?

At this time, no. No studies have shown that currently available tools or approaches are effective at preventing women from dying from ovarian cancer.

If there are no reliable screening tools, how is ovarian cancer diagnosed?

Once a physician suspects a woman has ovarian cancer (usually after a CA-125 test, ultrasound, and other tests), an exploratory surgical procedure called laparotomy is generally required for the definitive diagnosis of ovarian cancer.

During this procedure, cysts or other suspicious areas must be removed and biopsied. After the incision is made, the surgeon assesses the fluid and cells in the abdominal cavity. If the lesion is cancerous, the surgeon continues with a process called surgical staging to ascertain how far the cancer has spread. In select cases, aspiration of ascites that is caused by metastatic lesion or laparoscopy is used to confirm the diagnosis.

Why don’t doctors give women a CA-125 test and transvaginal ultrasound each year? Isn’t an imperfect screening tool better than nothing?

Studies have found that screening women at average risk of ovarian cancer did not improve the women’s odds of surviving ovarian cancer — and actually put them at greater risk due to complications from unnecessary surgeries.

A large study first published in Dec. 2015, called the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), showed that relying on the use of multiple CA-125 values taken over many years, combined with other factors and using an algorithm called ROCA — a more sophisticated approach than relying on CA-125 values alone — failed to prevent women from dying from ovarian cancer. Further results from the study published in May 2021 confirm the initial results, that ovarian cancer screening in the general public does not save lives. Read more on the study at the AAFP website, and see OCRA’s writeup on the most recent findings.

In another study, more than 78,000 women were randomized between normal care and screening arms. The screening protocol involved annual CA-125 testing for six years and a transvaginal ultrasound for four years. The study was designed to show the effect of screening on overall survival by following patients for 13 years. The study showed that more women were diagnosed in the screening arm, but more women died of ovarian cancer in the screening arm.

Additionally, more than 3,000 women had surgery based on false positive results, leading to more than 160 women with serious complications. This study showed that screening with this protocol did not reduce ovarian cancer mortality.

What is the ROCA Test?

The ROCA Test is a test that uses the change in CA-125 over time, combined with other factors (age, menopausal status, etc.), to predict risk of having ovarian cancer. The test must be ordered by a doctor, but can be purchased directly for $295. Though the ROCA Test is being marketed to women and encouraging them to ask for it as part of their annual check-up, there is no evidence that this test prevents women from dying from ovarian cancer. Read more here.

Is the ROCA Test safe?

In September 2016, the FDA issued a Safety Guidance on ovarian cancer screening tests, and specifically mentioned the ROCA Test when discussing ovarian cancer screening tests that may be unsafe for women.

Is the ROCA Test FDA approved?

The ROCA Test is not FDA approved, as FDA doesn’t traditionally carefully regulate these kinds of tests.