CLINICAL EVALUATION OF EARLY SCREENING STRATEGIES FOR OVARIAN CANCER IN HIGH‑RISK WOMEN

Abstract

Background: Ovarian cancer is the deadliest gynecologic cancer with only a five-year survival rate of less than 30 percent when the cancer is advanced and survival is over 90 percent when the cancer is detected at an early stage. Women who are at high risk such as those with BRCA1/2 and Lynch syndrome have a considerably high lifetime risk, but no screening protocol has clearly shown to reduce mortality. Methods: This systematic review and meta-analysis involved 47 eligible studies (12,843 high-risk women) to compare the diagnostic performance, stage distribution, mortality outcomes, and adverse events among six screening strategies: CA-125 alone, transvaginal ultrasound alone, Risk of Ovarian Cancer Algorithm (annual or semi-annual ultrasound), HE4 combined with CA-12 The bivariate random-effects models were used to compute pooled sensitivity, specificity, positive predictive value, and mortality rate ratios. Findings: The liquid biopsy panel had the highest diagnostic accuracy  and then HE4 with CA-125. Cancers detected by the screen were much more likely to be at an early stage than those detected by clinic. The liquid biopsy panel had the highest mortality reduction. False-positive rates between 38.5 and 245.2 per 1,000 screens have been found, however, with 22.4% of women in multimodal screening. BRCA1 carriers exhibited better positive predictive values and faster biomarker kinetics as compared to BRCA2 carriers. Conclusion: Liquid biopsy panel is the most precise and successful screening method in the high-risk women that could produce significant stage shift and mortality rates, but false positives and psychological morbidity are also a concern and should be implemented individually.