Based on a study that began in 2001, researchers have concluded that ovarian cancer screening increases survival. Disease-related mortality was 20% lower among women who received multimodal screening—annual testing of CA125 blood levels and, if CA125 was abnormal, additional CA125 tests and perhaps transvaginal ultrasound—than among those who weren't screened. When researchers factored in the delayed benefits of screening, the mortality reduction was 22%.

One of the largest and longest cancer screening studies suggests that ovarian cancer screening reduces mortality in postmenopausal women.

Ovarian cancer screening is not routine, and its effectiveness remains unclear. The only randomized study that has reported mortality data, the influential Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, completed in 2006, concluded that annual screening using transvaginal ultrasound and levels of CA125, a blood biomarker that may indicate ovarian cancer, did not reduce disease mortality.

The new trial, which began in 2001, included more than 202,000 women from the United Kingdom between the ages of 50 and 74. Researchers randomly assigned participants to receive no screening, annual transvaginal ultrasound, or multimodal screening, which involved different screening procedures depending on trends in CA125 levels. Women who had normal CA125 levels continued with annual tests; women with moderate levels had the test every 3 months; women with high levels had another CA125 measurement and a transvaginal ultrasound after 6 weeks. Screening continued through 2011, and the trial results, published recently in The Lancet, include survival data through 2014.

The researchers initially compared ovarian cancer mortality using two different statistical models and didn't find any significant differences between the unscreened patients and either of the screened groups. However, when they removed patients who already had ovarian cancer (but were unaware of it) when the trial began and reanalyzed the data with one of their models, they detected a significant benefit. Compared with no screening, multimodal screening resulted in a 20% decrease in ovarian cancer mortality.

When the researchers analyzed mortality over time, they detected a trend. “On average, it took 8 to 9 years before [the patients] developed ovarian cancer and deaths started to occur,” notes coauthor Ian Jacobs, MD, of the University of New South Wales in Australia. The statistical models the team first applied didn't account for this delay. A different statistical model that did factor in the effect showed that ovarian cancer mortality declined by 22% in patients who underwent multimodal screening. Annual transvaginal ultrasound also reduced mortality but didn't reach the threshold for statistical significance.

“The study is the first ever to suggest that the outcome of ovarian cancer can be changed through early detection by screening,” says Jacobs. “We need to continue to follow the women who took part in the trial for another 2 to 3 years to definitely confirm the mortality reduction.”

Women at high risk of the disease may want to consider annual screening after consulting their doctors, Jacobs adds. Before large-scale or national programs can begin, further evidence that screening is beneficial and cost-effective is necessary, he says.

“With longitudinal screening, we may be able to impact mortality by 15% to 25% or more,” says Ronny Drapkin, MD, PhD, of the University of Pennsylvania in Philadelphia, who wasn't connected to the research. That the mortality reduction increased in the latter half of the study is encouraging, he says. “The hope is that with a few more years of follow-up, the results will be more compelling and significant.”

“It's a very, very hopeful trial,” says John van Nagell, MD, of the University of Kentucky College of Medicine in Lexington. The results support further research into screening, he says, but the data aren't yet sufficient to warrant widespread screening. The trial is “not saying that everyone with an ultrasound in their office should open up a screening clinic.” –Mitch Leslie

©2016 American Association for Cancer Research.
2016
American Association for Cancer Research.