Personalizing CA125 levels for ovarian cancer screening

Abstract

Screening trials for the early detection of ovarian cancer in the general population and in patients at a high risk for this disease have so far failed to show a reduction of ovarian cancer-specific mortality. Current screening modalities include pelvic examinations, transvaginal ultrasounds, and cancer antigen 125 (CA125) serum marker levels, which are associated with a high false-positive rate. The last decade has witnessed significant modifications in the interpretation of serum CA125 that extend beyond a static CA125 cutoff point. The Risk of Ovarian Cancer Algorithm (ROCA) incorporates changes of CA125 levels over time and an individual's age-specific risk. Ongoing screening trials have incorporated ROCA, but it is still unclear whether the algorithm will increase the sensitivity and specificity of early ovarian cancer diagnosis. A very recent study analyzed baseline CA125 serum marker levels from high-risk patients included in ovarian cancer screening trials conducted by the Cancer Genetics Network and the Gynecologic Oncology Group. The findings show that the distribution of CA125 serum marker levels in this population is significantly affected by various demographic and clinical factors, in particular menopausal status and oral contraceptive use in premenopausal patients. The data suggest that CA125 cutoff points might have to be stratified for subgroups of patients to reduce false-positive results. These intriguing observations will need to be validated in future screening trials for ovarian cancer.