Lentz SE, Powell CB, Haque R, et al. - A longitudinal algorithm combining two biomarkers, CA125 and HE4, was developed that may allow early detection of ovarian cancer in women with BRCA mutations. Researchers conducted a novel ovarian cancer early detection prospective study including 149 women with BRCA mutations and intact ovaries. Every 4 months, they performed the Risk of Ovarian Cancer Algorithm (ROCA) identifying significant increases above each woman's baseline in serum CA125 and HE4; abnormal risks triggered a subsequent ultrasound. In this study, first a risk algorithm for only CA125 was used, then a second algorithm for HE4 was created and finally a risk algorithm combining the two biomarkers was applied. They performed enrollment of a total of 149 women in the ROCA arm while 43 women in the SOC arm. Observations revealed lower call-back rates in correlation with administration of the newly developed two-marker ROCA every 4 months vs SOC surveillance. The two-marker ROCA score was established to have high specificity, deserves further evaluation for sensitivity in a larger trial.