Abstract Ovarian cancer is a leading cause of gynecological cancer mortality. Despite the widespread use of cancer antigen 125 (CA125), its sensitivity for early-stage detection is limited. This review evaluates the diagnostic accuracy of CA125, Human epididymis protein 4 (HE4), Risk of Ovarian Malignancy Algorithm (ROMA), and the Assessment of Different Neoplasia's in the adneXa (ADNEX) model in distinguishing benign from malignant ovarian masses. A systematic review was conducted using PubMed, Embase, and Scopus, selecting studies published up to June 2025. Studies were included if they provided data on the diagnostic accuracy of HE4, CA125, ROMA, or ADNEX in women with pelvic masses. A total of seven studies met the inclusion criteria. ROMA demonstrated high diagnostic performance, with sensitivity ranging from 64.8 to 93.75% and specificity from 72.8 to 94.9%, particularly in postmenopausal women. Although CA125 showed a sensitivity of 85.07% in one study, several other studies reported higher sensitivity for ROMA, particularly in postmenopausal women, as well as higher specificity (92.31%). HE4 exhibited very high specificity (up to 97.87%) but demonstrated variable sensitivity across studies, outperforming ROMA in some cohorts, such as Montagnana et al. ROMA performed comparably to Risk of Malignancy Index (RMI) in some studies, although RMI demonstrated slightly higher overall accuracy in Anton et al and outperformed CA125 in several studies. The ADNEX model showed higher sensitivity (91.9%) but lower specificity (65.7%) compared with ROMA. ROMA is a valuable diagnostic tool, especially in postmenopausal women, offering better diagnostic accuracy than CA125 alone, with sensitivity as high as 93.75% and specificity up to 94.9%. However, its sensitivity in premenopausal women is limited. Further research is needed to optimize ROMA's cutoff values and improve its integration with other diagnostic methods.
Mirzaeva et al. (Mon,) studied this question.