Estimating the Opportunity for Early Detection of Ovarian Cancer Using Individual-Patient Data from a Large Randomized Controlled Trial.

The UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) did not detect a reduction in ovarian cancer (OC) mortality with either multimodal screening (MMS) or transvaginal ultrasound screening (USS) compared to no screening. The trial data provide an invaluable resource to quantify the opportunity for interception in OC. We used Bayesian inference to estimate OC natural history based on individual screening and cancer diagnosis records from UKCTOCS, a randomized controlled OC screening trial conducted in England, Wales, and Northern Ireland. The trial included 202,638 women aged 50 to 74 years with no family history of OC, randomized in a 1:1:2 ratio to annual MMS (serum CA125 interpreted using the Risk of Ovarian Cancer Algorithm), annual USS, or no screening. The current analysis included 199,499 women, with 674,806 screens and 2,025 cancer diagnoses. Among high-grade serous cancers (HGSCs), the estimated preclinical detectable phase (PCDP) was 1.7 years (95% credible interval CI, 1.3-2.2), compared with 7.8 years (95% CI, 5.7-10.6) for non-HGSCs. The PCDP depended on screening modality: for HGSCs, it was longer in the MMS arm (2.2 years) compared with the USS arm (0.8 years), whereas for non-HGSCs, it was shorter in the MMS arm (2.7 years) compared with the USS arm (8.2 years). The interception opportunity for OC strongly depends on histological subtype and screening modality. Achieving a clinically significant benefit of OC early detection will require prolonging the interception window through judicious combination of first- and second-line tests.