Early detection of ovarian cancer through regularly repeated screening tests offers hope for mortality reduction. Over 75% of ovarian cancers are detected in late stage when prognosis is very poor, while detection when disease is limited to the ovaries has excellent prognosis, making ovarian cancer an ideal target for disease interception. Serum CA125 is an ovarian cancer biomarker approved for clinical management of ovarian cancer, typically interpreted using a cutoff level. However, using each woman as her own control and detecting significant rises above her baseline CA125 level may detect ovarian cancer earlier than using a single cutoff. Over the past 20 years, multiple screening trials applied personalized CA125 testing and found a significant increase in early stage detection. Longitudinal interpretation works best when the cancer arises after a baseline has already been measured, and less well for prevalent cases where the CA125 is already on the rise at the first screen. Therefore evaluation of this approach should analyze results grouped separately into incident and prevalent cases, similar to the evaluation of targeted therapies grouped by breast cancers with and without EGFR mutations. In contrast to trials using a fixed cutoff, all trials using the personalized approach increased the proportion detected in early stages, with evidence in the largest trial of a mortality reduction in the incident cases.