A doctor talks about screening for ovarian cancer

Celeste Robb-Nicholson, M.D.

(This article was first printed in the September 2004 issue of the Harvard Women's Health Watch. For more information or to order, please go to www.health.harvard.edu/womens.)

Some of my patients have received an alarming e-mail urging women to have a CA-125 test for ovarian cancer. CA-125 is a protein often made by ovarian cancer that circulates in the blood. Levels of CA-125 are elevated in about 80% of women with advanced ovarian cancer and 50% of those with early-stage disease. I understand why patients ask me to be tested. Ovarian cancer is the fifth leading cause of cancer death among women in the United States. When detected early, it can be successfully treated. However, most ovarian cancer is found only after it has spread beyond the ovaries. It makes sense to look for a simple test that detects the cancer an early stage. Unfortunately, the CA-125 blood test does not qualify.

What’s a good screening test?

A screening test is done in a person with no symptoms in order to find disease early enough that diagnosis will improve survival. A good screening test should be very sensitive, meaning it’s positive when an illness is present. In this case, a test that’s 100% sensitive would detect all cases of ovarian cancer. A screening test should also be very specific; that is, it’s negative when there’s no cancer. 

As a screening test, CA-125 is generally not useful. First, it can miss as many as half of all women with early-stage cancer. Second, it’s not specific enough. Other conditions, such as endometriosis, fibroids, and pelvic infections, or even ovulation, can elevate CA-125.

Specificity is extremely important in ovarian cancer screening, because the condition affects a relatively small number of women — 1 in 2,500 every year. To understand the problem, consider an imaginary representative group of 2,500 women, and suppose our test is 100% sensitive (it will identify every woman with the disease). Now suppose the specificity is 99%, meaning that 1% of the women would test positive even though they didn’t have ovarian cancer.

In testing our group of 2,500 women, we would identify one woman with ovarian cancer, but we’d also get false positive results for 25 women. And, unfortunately, invasive surgery is the only way to find out for sure if a woman has ovarian cancer. In other words, to locate the one woman in 2,500 who actually had the disease, we’d subject 25 others to unnecessary abdominal surgery.

If you expand our test group to include all U.S. women, the number of unnecessary surgeries would be huge. Thus, the risk of testing would outweigh the benefits.

Testing with CA-125

The CA-125 blood test can be useful, but only for women known to be at higher risk, so that there are fewer false positives. CA-125 testing along with transvaginal ultrasound can help evaluate women with suspected ovarian cancer. It’s also used to monitor ovarian cancer treatment. (Transvaginal ultrasound involves inserting a transducer into the vagina to obtain ultrasound images of the ovaries.) In addition, many experts recommend the combination test for women who are genetically at high-risk for ovarian cancer. This includes women who have a mother, sister, daughter, grandmother, aunt, or niece with ovarian cancer. Carriers of the BRCA1 or BRCA2 gene mutations are also at increased risk.

Among these women, a positive CA-125 test is more likely to be a true positive, possibly making the risk of invasive surgery one worth taking.

On the horizon

A new method of cancer detection is proteomic pattern recognition, which identifies patterns of proteins in the blood characteristic of cancer. Researchers from the National Cancer Institute (NCI), the FDA, and a company called Correlogic Systems, Inc., have discovered a pattern of proteins apparently unique to ovarian cancer. The researchers looked for the pattern in 116 women with and without ovarian cancer. They correctly classified 95% of healthy women as not having cancer and identified 100% of cancer samples, including a few with early disease (Lancet, Feb. 16, 2002).

Based on these results, Correlogic developed a blood test called OvaCheck, but it’s been stalled in moving into the marketplace. Although it appears to be more sensitive than combined CA-125 and ultrasound, OvaCheck hasn’t been compared to the combination “head-to-head.” Also, other researchers have been unable to replicate the results reported in the Lancet study. Finally, very few women have been tested with OvaCheck. Before it’s made available to all women, OvaCheck needs to be tested in larger groups and proven effective in detecting the cancer at an early stage, when it’s curable. Meanwhile, the FDA, NCI, and scientists around the world are honing the new technique.

What now?

In the absence of a good screening test, I encourage women to pay attention to new abdominal or pelvic symptoms. If you have a sudden increase in your abdominal size, bloating, or very frequent and severe urinary urgency or pelvic pain, see your doctor. One survey of women in a general practice clinic found that cluster of symptoms tended to occur suddenly, frequently (20–30 times per month), and severely in women who were ultimately diagnosed with ovarian cancer. These symptoms are common and easy to ignore. But if they persist, you should have a pelvic examination and possibly transvaginal ultrasound.

(This article was first printed in the September 2004 issue of the Harvard Women's Health Watch. For more information or to order, please go to www.health.harvard.edu/womens.)

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