Human epididymis protein 4 offers superior specificity in the differentiation of benign and malignant adnexal masses in premenopausal women.

OBJECTIVE: We sought to assess the ability of human epididymis protein 4 (HE4) and CA-125 to distinguish among benign, borderline, and malignant pelvic masses in premenopausal women. STUDY DESIGN: We conducted a subset analysis of data from a prospective clinical trial that enrolled women undergoing surgery for an adnexal mass. Diagnostic performance of CA-125 and HE4 for epithelial ovarian cancer (EOC) detection in premenopausal women was determined. RESULTS: Of 229 premenopausal patients, 195 (85%) had benign masses, 18 (8%) had EOC, and 16 (7%) had borderline ovarian tumor. The sensitivity of CA-125 and HE4 for EOC detection was 83.3% and 88.9%, respectively. The specificity of CA-125 and HE4 was 59.5% and 91.8%, respectively. A normal HE4 level ruled out invasive cancer in 98% of women with an elevated CA-125. CONCLUSION: HE4 offers superior specificity compared to CA-125 for the differentiation of benign and malignant adnexal masses in premenopausal women.

Calculation of the risk of ovarian cancer from serial CA-125 values for preclinical detection in postmenopausal women.

PURPOSE: Previous studies of CA-125 levels from screening trials for ovarian cancer have indicated that serial CA-125 levels may identify cases better than a fixed CA-125 cutoff. We conducted a study to assess the screening performance of the risk of ovarian cancer calculation based on serial CA-125 levels from prospectively collected serum samples compared with a fixed CA-125 cutoff. PATIENTS AND METHODS: The calculation was applied to data from a prospective trial of screening for ovarian cancer involving 22,000 postmenopausal women older than 45 years. The analysis was performed using 33,621 CA-125 results from 9,233 women for whom two or more serial samples were available. All serum samples from the patients with ovarian cancer were obtained before clinical detection. Sensitivity and specificity levels for preclinical detection of index cancers were calculated for various cutoffs for the risk and a single CA-125 measurement, and receiver operator curves were constructed. RESULTS: The risk calculation significantly improved the area under the curve from 84% to 93% compared with a fixed cutoff for CA-125 (P =.01). For a target specificity of 98%, the risk achieved a sensitivity of 86% for preclinical detection of ovarian cancer, whereas CA-125 achieved a sensitivity of 62%. The estimates of performance are unbiased, because the risk calculation was derived independent of the data from this trial. CONCLUSION: These results provide the first evidence that preclinical detection of ovarian cancer using serial CA-125 levels interpreted with the risk calculation significantly improves screening performance compared with a fixed cutoff for CA-125. The results justify the incorporation of the risk calculation in a prospective, randomized, controlled trial.