Why has ovarian cancer screening eluded researchers for 4 decades?

No FDA-approved screening test for ovarian cancer currently exists, despite roughly 4 decades of research aimed at developing one, according to Dawn Mattoon, PhD, CEO of Mercy BioAnalytics, Inc. The investigational Evident Ovarian Cancer Screening Test, a blood-based assay that analyzes tumor-derived extracellular vesicles, was developed to address that gap, and its clinical validation drew directly on samples from one of the most visible failures in ovarian cancer screening research.

That trial, the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), evaluated serum CA-125 and transvaginal ultrasound as candidate screening modalities. Approximately 200,000 women enrolled, and each provided a blood sample at the time of enrollment. Participants were then followed through National Health Service health records for 20 years, Mattoon said. Of those enrolled, 100,000 women were randomly assigned to no screening, 50,000 to annual pelvic imaging with transvaginal ultrasound, and 50,000 to annual CA-125 testing interpreted through the risk of ovarian cancer algorithm.¹

UKCTOCS was designed to establish a mortality benefit for 1 or both screening modalities, and it did not reach that end point.¹ Because the trial was so large, a substantial number of ovarian cancer cases were diagnosed across the randomization arms, Mattoon noted. The research community has mourned the result, and screening with these modalities is not currently recommended in guidelines.² According to Mattoon, guideline communications have also explicitly called for tests with better performance and the potential to deliver the mortality benefit that UKCTOCS sought.

The archived UKCTOCS samples, collected at enrollment and linked to long-term follow-up records, have since served as the foundation for clinical validation of the Evident test. That work was conducted through a collaboration with University College London and the investigators who ran the original trial, which Mattoon described as highly productive.

“We’ve had the opportunity now to demonstrate superior performance relative to the modalities that were used in the trial, in the actual samples from the trial,” Mattoon said.

Mattoon framed this approach as a way to recover value from the substantial investment of resources and participants that UKCTOCS represented. Rather than treating the trial solely as evidence that screening does not work, her team has used its banked samples to compare a newer modality directly against the approaches the trial tested.

“I think it’s such an amazing opportunity to take the hundreds of millions of dollars and 200,000 women who participated in that trial and transform it from a failed trial to actually the enabling study that will, we think, ultimately support our FDA approval,” Mattoon said.

The Evident test has not been approved or cleared by the FDA. In September 2026, the FDA approved an investigational device exemption allowing Mercy BioAnalytics to begin SOARA, a prospective pivotal study of the test in average-risk women.

References

1. Menon U, Gentry-Maharaj A, Burnell M, et al. Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. 2021;397(10290):2182-2193. doi:10.1016/S0140-6736(21)00731-5

2. US Preventive Services Task Force; Grossman DC, Curry SJ, Owens DK, et al. Screening for ovarian cancer: US Preventive Services Task Force recommendation statement. JAMA. 2018;319(6):588-594. doi:10.1001/jama.2017.21926