Discriminative value of CA-125, HE4, Risk of Malignancy Index II (RMI-II) and Risk of Malignancy Algorithm (ROMA) in the differential diagnosis of pelvic masses: conclusions from a referral Centre in Portugal

Abstract

The major purpose of this article was to compare the discriminative value of different algorithms and serum biomarkers in the differential diagnosis of adnexal masses. We performed a retrospective study with 247 women with adnexal neoplasia, submitted to surgical treatment and with a histological diagnosis. The evaluation of the area under the curve (AUC) for isolated CA-125 and HE4, and for ROMA and RMI-II, showed a better specificity of HE4 and RMI-II in premenopausal women. In the postmenopausal group, ROMA and RMI-II were the algorithms with a better performance. Impact Statement What is already known on this subject? CA-125 remains the most commonly used biomarker used to predict the behaviour of an adnexal mass, but it has a low sensitivity for stage I tumours. Other isolated serum markers have emerged more recently, such as HE4, as well as more complex algorithms, such as RMI or ROMA. It remains unclear which is the best marker/algorithm to predict the behaviour of an adnexal mass. What do the results of this study add? Our findings showed that ROMA is a suitable marker for postmenopausal women, with no advantage found in the premenopausal women when compared with an isolated HE4. What are the implications of these findings for clinical practice and/or further research? The different algorithms of the preoperative discrimination of ovarian neoplasia appear to have different AUC, SN and SP in the pre- or the postmenopausal patients. For the premenopausal women, the use of ROMA does not seem to have any advantage over the isolated use of HE4, which does not lose specificity even when the borderline tumours are considered for discrimination. In the postmenopausal women, ROMA is a valid algorithm with a good sensitivity. The RMI-II showed a good performance in both groups, although it depends on the ultrasound findings and has an important interobserver variability. This information allows a more targeted selection of markers and algorithms to be requested prior to surgery of ovarian neoplasms regarding the menopausal status of each patient.

ESGO/ISUOG/IOTA/ESGE Consensus Statement on preoperative diagnosis of ovarian tumors

“…Multiple studies, including meta‐analyses, have highlighted the role of HE4 as a potential complement to CA 125, especially in differentiating benign endometriotic and inflammatory lesions in younger women 25,81–103 . Additional tumor markers (as in the ROMA test) have failed to improve significantly the discrimination between benign and malignant masses compared with CA 125 alone 53,81,84,91,96–109 .…”

“…Multiple studies, including meta‐analyses, have highlighted the role of HE4 as a potential complement to CA 125, especially in differentiating benign endometriotic and inflammatory lesions in younger women 25,81–103 . Additional tumor markers (as in the ROMA test) have failed to improve significantly the discrimination between benign and malignant masses compared with CA 125 alone 53,81,84,91,96–109 . The combination of a more extended tumor marker profile, including the addition of carcinoembryonic antigen (CEA) and/or carbohydrate antigen (CA 19‐9) to CA 125, is useful mainly for differentiating between metastatic tumors from the gastrointestinal tract or pancreas and primary ovarian malignancy 110–113 .…”

Diagnostic measures comparison for ovarian malignancy risk in Epithelial ovarian cancer patients: a meta-analysis

“…1 ) shows the stages of the studies screened and included for the analysis, and 32 studies 15 – 46 met the inclusion criteria. The number of studies included for HE4, CA125 and ROMA tests were 25 16 – 19 , 22 – 32 , 34 , 35 , 37 – 43 , 26 16 – 20 , 22 – 35 , 37 – 41 , 43 and 22 15 – 18 , 20 , 21 , 26 – 29 , 31 , 34 – 43 , 46 , respectively. The patients with EOC were taken as cases, and women with benign ovarian mass were taken as control, which was 2233/5682, 2315/5875 and 2281/5068, respectively, for the markers or algorithm (Table 1 ).…”

ESGO/ISUOG/IOTA/ESGE Consensus Statement on preoperative diagnosis of ovarian tumours

“…Multiple studies, including meta-analyses, have highlighted the role of HE4 as a potential complement to CA 125, especially in differentiating benign endometriotic and inflammatory lesions in younger women (Al Musalhi et al, 2016;Cao et al, 2018;Huang et al, 2018;Jacob et al, 2011;Jia et al, 2017;Kim et al, 2019;Kotowicz et al, 2015;Li et al, 2012;Lin et al, 2013;Lycke et al, 2018;Melo et al, 2018;Richards et al, 2015;Romagnolo et al, 2016;Sandri et al, 2013;Shin et al, 2020;Stiekema et al, 2014;Terlikowska et al, 2016;Van Gorp et al, 2012;Wang et al, 2014;Xu et al, 2016;Yanaranop et al, 2017;Yanaranop et al, 2018;Yu et al, 2012;Zhang et al, 2015). Additional tumour markers (as in the ROMA test) have failed to improve significantly the discrimination between benign and malignant masses compared with CA 125 alone (Chen et al, 2015;Choi et al, 2020;Cui et al, 2019;Huy et al, 2018;Kaijser, Van Gorp, et al, 2014;Kim et al, 2019;Kotowicz et al, 2015;Lycke et al, 2018;Melo et al, 2018;Piovano et al, 2017;Romagnolo et al, 2016;Sandri et al, 2013;…”