Ovarian cancer is the fourth-leading cause of cancer deaths among women in the U.S., but unlike with breast cancer, there is no mammogram equivalent that can seek out early lesions before they become difficult to treat.
A blood test, called CA125, can pick up signs of tumors in the ovaries, but it’s not very specific or sensitive for these growths. CA125 levels can rise not just because of ovarian tumors but during menstruation and pregnancy as well. That may explain why the test only picks up 60% to 65% of cancers.
But scientists report in The Lancet that there may be a way to pick up early ovarian tumors and potentially save lives. Ian Jacobs, president and vice chancellor of the University of New South Wales, and his colleagues conducted the largest study to date on an innovative way to use CA125 testing to screen women for ovarian cancer. Jacobs created an algorithm that incorporated several CA125 readings over time, with a woman’s age, to tighten the blood test’s connection to ovarian cancer risk.
A single CA125 reading may not be helpful, he notes, since women may have varying baseline levels of the substance. Even if the cutoff for possible ovarian cancer is any result above 35microns/ml, for example, some women may simply have higher circulating CA125 and not have cancer. But if several readings over a few years show that the CA125 is increasing rapidly, that’s a signal that a tumor could be growing.
Jacobs randomly assigned more than 202,000 women to get either no screening, only ultrasound screening or a combination of CA125 using the algorithm every year for an average of 11 years. He wanted to test whether the CA125 test along with its algorithm could be an effective way to screen women for ovarian cancer, so after a follow up of about 14 years, he compared these three groups of women on whether they had developed ovarian cancer or not, and whether they had died from the disease.
Overall, the women who received the CA125 screening with the algorithm lowered their risk of dying from ovarian cancer by 15%, while those who relied only on ultrasound reduced their risk of dying by 11%. That wasn’t a statistically significant difference, but when the researchers adjusted those results for the effect from women who might have already had ovarian cancer before starting the study but didn’t know it, the reduction was even more dramatic for women screened with CA125: 28%.
“The exciting thing about this paper is that it’s the first evidence that suggests if you catch the cancer early enough, perhaps it can save lives,” says Jacobs.
Dr. Karen Lu, chair of gynecologic oncology and reproductive medicine at University of Texas MD Anderson Cancer, welcomes the results. “I’m tired of seeing women come to me with late-stage disease,” says Lu, who was not involved in the study but has conducted trials on using annual CA125 and other markers to screen for ovarian cancer. “It’s devastating. About 70% of the time, if not more, we see women come to us with very advanced stage disease. What this study clearly shows is that with the CA125 test and the algorithm, we are detecting cancers at an earlier stage. And we’re seeing fewer deaths in women who get the screening. We’ve never had a study before that showed that early detection [of ovarian cancer] can save lives.”
Lu points out, however, that the data on CA125 screening and lower deaths from ovarian cancer is still preliminary, and that longer follow-up of the women, which Jacobs is doing, will be needed to solidify the survival benefit.
Still, the findings represent a rare glimmer of optimism in diagnosing and treating a cancer that usually has poor prognosis. If the results are confirmed, then additional studies will have to be performed to determine which women should be getting screened. The target population may be as wide as all post-menopausal women, says Lu. (Women who have the BRCA1 or BRCA2 mutations that put them at higher risk of both breast and ovarian cancers wouldn’t likely need the screening, since they already know they are at high risk.) As with mammography, the costs of screening, including the false positives that result in additional testing and procedures, need to be weighed against the benefits in detecting cancer earlier. If the CA125 does become part of the cancer screening regimen, then women would get the blood test on an annual basis, and if their levels are rising, they would get an ultrasound to see if there are any abnormal growths in the ovaries. If the ultrasound finds lesions, then she could get surgery to remove them and significantly lower her risk of dying from the disease.
Jacobs is currently working with a company to develop the CA125 algorithm into a commercial test. He sees this study as “a key step in the jigsaw [puzzle] that is about 85% assembled now,” he says. “It is a paradigm shift in showing that you can actually intervene by screening and change the natural history of the disease and likely save lives.” But even he acknowledges that it may be a while before the test becomes part of national screening recommendations like the mammogram. “We need longer follow up,” he says. “But we are not that far away.”