CA-125: What the Numbers Tell Us

CURE, Spring 2011, Volume 10, Issue 1

Researchers are looking for effective screening methods for ovarian cancer.

More than 80 percent of ovarian cancers are found after they spread, which is why researchers are looking for a way to effectively screen for ovarian cancer. Many of them are looking at one biomarker in particular, CA-125.

CA-125 (cancer antigen 125) is a protein produced on the surface of cells that then circulates in the blood. High amounts of CA-125 in the blood (generally more than 35 units per mL) could be a sign of ovarian cancer. If someone has symptoms related to ovarian cancer, such as bloating, pelvic or abdominal pain, the test can be one of the first steps to check for the disease. Physicians also look at CA-125 levels to determine if the cancer is responding to chemotherapy and to monitor for recurrence.

However, this biomarker test is imperfect. Elevated CA-125 levels can be caused by a variety of other factors, such as pregnancy, menstruation, endometriosis and other types of cancer. These “false-positive” results can lead to unnecessary tests or procedures (such as invasive surgery). There are also “false-negatives” associated with the test—about 20 percent of women with ovarian cancer don’t have elevated CA-125 levels. And the test particularly lacks specificity in premenopausal women.

Due to the test’s inaccuracy, widespread screening for ovarian cancer isn’t recommended. Furthermore, a study, published online Dec. 13 in Cancer, found only a slight benefit in widespread screening. By using a model to examine data in the National Institute of Health’s Surveillance, Epidemiology, and End Results database, researchers found that annual screening in postmenopausal women would reduce mortality from ovarian cancer by 10.9 to 14.7 percent.

Despite these findings, researchers continue to look for ways to improve the CA-125 test and how it can be combined with other methods for more effective screening. In a study presented at the annual meeting of ASCO, researchers used an algorithm in conjunction with CA-125 tests to screen for ovarian cancer. The formula calculates a woman’s risk for the disease based on her age, baseline CA-125 level and subsequent annual CA-125 tests, so it measures not just the CA-125 level, but the rate of change over time.

Investigators followed 3,238 women at average risk for ovarian cancer for up to nine years and reported that no invasive cancers were missed by this screening method. Of the eight women who had surgery, five were diagnosed at early stage and three had benign lesions. Before a change in practice can occur, follow-up studies will be needed to confirm results. Meanwhile, an ongoing trial in the U.K. is examining this method of screening in more than 200,000 women and expects to release results in 2015. If the results are similar to the U.S. study, then it may mean a screening strategy for ovarian cancer is one step closer to being developed.