Simmons AR, et al. - The notion that multiple biomarkers could detect ovarian cancer cases missed by CA125 led researchers to assess the sensitivity and lead time of a multi-marker panel (CA125, HE4, MMP-7, and CA 72-4) vs CA125 alone. For this purpose, they analyzed selected preclinical longitudinal specimens from 75 women who developed invasive epithelial ovarian cancer and 547 corresponding healthy controls recruited from the UKCTOCS trial. Using single-marker longitudinal algorithms (risk of ovarian cancer algorithm-like) developed in this study, 16% (4/25) of screen-negative cases were identified by HE4 and CA72-4, while MMP-7 identified none, all at 98% specificity. Overall, they concluded that the use of HE4 and CA72-4 as complementary biomarkers to CA125 has promise for longitudinal screening.