New Multimodal Ovarian Cancer Screening Tactic Shows Promise

A new method of screening utilizing CA-125 and a risk assessment algorithm could drop risk of mortality from ovarian cancer in certain women, according to findings from the UK Collaborative Trial of Ovarian Cancer Screening.

Ian Jacobs, MBBS, MD, BA, MA, FRCOG

A new method of screening utilizing CA-125 and a risk assessment algorithm could drop risk of mortality from ovarian cancer in certain women, according to findings from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

The findings, published in The Lancet, showed that when compared to women who receieved no screening there, was a 20% reduction in the risk of death for women screened using CA-125 and risk assessment tools. This is after excluding those in the trial who were diagnosed with cancer prior to being screened (P = .021).

In the full population, however, a statistically significant reduction in mortality from ovarian cancer was not seen with screening using ultrasound alone or for risk assessment with CA-125 testing.

“The evidence from UKCTOCS suggests that carefully conducted screening using a multimodal strategy detects ovarian cancer sufficiently early to alter the natural history of the disease and reduce mortality,” co-principal investigator Ian Jacobs, MBBS, MD, BA, MA, FRCOG, president and vice-chancellor of University of New South Wales, Australia, said in a statement.

“We are excited and encouraged by these results, demonstrating an estimated mortality reduction attributable to ovarian cancer screening of 15% to 28%. Further follow up in UKCTOCS will provide greater confidence about the precise reduction in mortality which is achievable.”

In the study, 202,638 postmenopausal women were randomized in 1:1:2 ratios to annual multimodal screening (n = 50,640), annual transvaginal ultrasound screening (n = 50,639), or no screening (n = 101,359). The multimodal screening approach included serum CA-125 testing and interpretation using the risk of ovarian cancer algorithm (ROCA). For those ranked as intermediate or elevated risk, repeat CA-125 was conducted with or without ultrasound, based on risk.

Patients in the trial were ages 50 to 85 and those with an increased risk of familial ovarian cancer were excluded from the study. Patient characteristics were well balanced between the arms, including race, number of children, oral contraceptive pill use, hormonal replacement therapy use, maternal history of cancer, and personal history of cancer.

The primary endpoint of the study was a comparison of death rates between each arm. Screening in the study ended on December 31, 2011. A secondary endpoint looked at mortality reduction in women with prevalent cases, defined as ovarian cancer that occurred before screening started.

After a median follow-up of 11.1 years, ovarian cancer was diagnosed in 0.6% (n = 1282) of women in the full population of the study. Of those diagnosed, 338 were identified in the multimodal group (26.4%), 314 were seen by ultrasound (24.5%), and 630 were identified in the group without screening (49.1%).

At the follow-up period, 739 women had died from ovarian cancer, 148 in the multimodal arm (20%), 154 in the ultrasound group (20.9%), and 437 without screening (59.1%). Overall mortality was reduced by multimodal screening by 15% over years 0 to 14; however, this was not statistically significant (95% CI, -3-30; P = .10). Additionally, in the ultrasound arm, a non-statistically significant 11% reduction in mortality was seen (95% CI, -7-27; P = .21).

During the first 7 years of the study, the reduction in mortality rate with multimodal screening was 8% compared with 23% for years 7 to 14. Similar findings were observed in the ultrasound cohort, with a reduction in mortality of 2% and 21% during years 0 to 7 and 7 to 14, respectively.

For the secondary analysis that removed prevalent cases, which accounted for 18% to 19% of diagnoses, there was an 8% reduction in mortality during years 0 to 7 with multimodal screening versus no screening. During years 7 to 14, the reduction in mortality with multimodal screening was 28% versus no screening.

More patients in the multimodal arm were diagnosed with low-volume invasive epithelial ovarian and peritoneal cancer compared with the group without screening. In the multimodal group, 40% of diagnoses were low volume disease versus 26% in the group without screening (P <.0001). In the ultrasound arm, 24% of patients were diagnosed with low volume disease.

“I am delighted that the UKCTOCS results suggest that early detection by screening may reduce mortality,” study coauthor Steven Skates, PhD, Massachusetts General Hospital, said in a statement. “We look forward to ongoing analysis of this study population in order to more fully understand how a multimodal, algorithm-dependent ovarian cancer screening program might specifically affect disease diagnosis and management.”


  1. Jacobs IJ, Menon U, Ryan A, et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial [Published online December 17, 2015]. Lancet. S0140-6736(15)01224-6.