Introduction/Background Several studies has shown no advantages of Risk of Ovarian Malignancy Algorithm (ROMA) over CA125 and/or HE4 tumor markers alone when ROC-AUC were analyzed. However, the best way of clinical interpretation of CA125/HE4 levels remains unclear. The goal of the study was to comprehensively evaluate several ways of clinical interpretation of CA125/HE4 serum levels in patients with pelvic mass.

Methodology We analyzed Ca125 and HE4 serum levels in 145 healthy females and in 1019 patients with pelvic mass, scheduled to have surgery.

Results In healthy women 95th percentile (90% Confidence Interval) of HE4 levels were 38.5(37.5–41.2) and 45.8(41.6–48.1) pmol/L in pre- and post-menopause respectively. When the manufacturer’s reference limits were used as a threshold, HE4 showed a sensitivity for epithelial ovarian cancer of 54% and a specificity of 98.8%. When our local reference population’s reference limits were used, the sensitivity and specificity of HE4 were of 94.7% and of 55.9% respectively. CA125 showed a sensitivity of 96.7% and a specificity of 73.7% according to the 35 U/ml threshold. The sensitivity and specificity of ROMA according to its standard cut-off limits were 89.2 and 88% respectively. Even when calculated optimal cut-off levels of CA125 and HE4 and standard cut-off level for ROMA were used, ROMA showed a tendency to a higher performance and a more balanced sensitivity/specificity than CA125/HE4 alone.

Conclusion Reference limits of CA125/HE4 (not proposed by the manufacturer, not determined in a reference population) do not correspond to the optimal cut-off levels and are not of clinical significance in patients with pelvic mass. ROMA performs better in a clinical setting than CA125/HE4 alone even if optimized cut-off levels (instead of reference limits) of these markers are used.

Disclosure Nothing to disclose.