Preoperative HE4 and ROMA values do not improve the CA125 diagnostic value for borderline tumors of the ovary (BOT) – a study of the TOC Consortium

Abstract

BackgroundBorderline tumors of the ovary (BOT) are a distinct entity of ovarian tumors, characterized by lack of stromal invasion. Recent studies postulated that the presence of invasive implants, incomplete staging, fertility sparing surgery and residual tumor after surgery are major prognostic factors for BOT. There are no biomarkers that can predict BOT or the presence of invasive implants.ObjectiveThe aim of our study was to assess the value of CA125 and HE4 alone, or within ROMA score for detecting BOT, and for predicting the presence of invasive implants.MethodsRetrospective, monocentric study on 167 women diagnosed with BOT or benign ovarian masses. Serum HE4, CA125 levels and ROMA were assessed preoperatively. Due to low number of BOT with invasive implants, we performed an unmatched analysis (consecutive patients) and a matched analysis (according to age and histology) to compare BOT with invasive implants, BOT without invasive implants and benign disease.ResultsThere were no significant differences in the HE4 and CA125 expressions in the three groups of patients (p = 0.984 and p = 0.141, respectively). The ROC analysis showed that CA125 alone is superior to ROMA and HE4 in discriminating patients with BOT with invasive implants from patients with benign diseases and BOT without invasive implants. A newly established score, ROMABOT, did not perform better than ROMA. The analysis of the matched groups revealed similar results as the analysis of all samples.ConclusionsBoth HE4 and CA125 are not reliable biomarkers for the diagnosis of BOT or for predicting the presence of invasive implants.

Comparison of HE4, CA125, and Risk of Ovarian Malignancy Algorithm in the Prediction of Ovarian Cancer in Korean Women

“…A recent prospective study suggested that ROMA, and also HE4 alone, showed similar performance to CA125 alone in pre-menopausal women, but worse performance in postmenopausal women ( 22 ). In another retrospective study, HE4 was not superior to CA125 in predicting borderline ovarian tumors or presence of invasive implants ( 35 ).…”

Physiopathological factors affecting the diagnostic value of serum HE4-test for gynecologic malignancies

“…Divergent results were reported by Braicu and his colleagues [69]. Studies on subjects covering 63 BOT patients and 104 patients with benign diseases of ovarian fibrothecoma and uterine leiomyomata found that serum HE4 was elevated only in postmenopausal BOT cases, but not in premenopausal BOT patients.…”

Validation of a Novel Biomarker Panel for the Detection of Ovarian Cancer

“…The serum-based Risk of Malignancy Algorithm (ROMA) and OVA1 ™ tests also represent relatively new multimarker algorithms for the management of ovarian cancer. Although both tests have seen some success leading up to FDA-approval, there are still conflicting results as to how well they truly perform compared to CA125 [30–34]. Furthermore, due to the fact that the algorithms rely heavily on serum levels of CA125 and/or HE4, they are susceptible to bias towards patients with late-stage cancers and/or serous carcinoma (most often high-grade serous carcinoma) [35].…”