Efficacy of HE4, CA125, Risk of Malignancy Index and Risk of Ovarian Malignancy Index to Detect Ovarian Cancer in Women with Presumed Benign Ovarian Tumours: A Prospective, Multicentre Trial.

Vincent Dochez,Edouard Vaucel,Hélène Caillon,Norbert Winer,Jérôme Dimet,Guillaume Ducarme,Thibault Thubert,Céline Renaudeau,Aurélie Le Thuaut,Mélanie Randet

doi:10.3390/jcm8111784

Abstract

Background: Presumed benign ovarian tumours (PBOT) are defined by the International Ovarian Tumour Analysis (IOTA) group, without suspected sonographic criteria of cancer, without ascites or metastasis. The aim is to evaluate the efficacy of human epididymis protein 4 (HE4), cancer antigen 125 (CA125), the risk of malignancy index (RMI) and the risk of ovarian malignancy index (ROMA) to predict ovarian cancer in women with PBOT. Methods: It is a prospective, observational, multicentre, laboratory-based study including women with PBOT in four hospitals from 11 May 2015 through 12 May 2016. Preoperative CA125 and HE4 plasma levels were measured for all women. The primary endpoint was the specificity of CA125 and HE4 for diagnosing ovarian cancer. The main secondary endpoints were specificity and likelihood ratio of RMI, ROMA and tumours markers. Results: Two hundred and fifty patients were initially enrolled and 221 patients were finally analysed, including 209 benign ovarian tumours (94.6%) and 12 malignant ovarian tumours (5.4%). The malignant group had significantly higher mean values of HE4, CA125, RMI and ROMA compared to the benign group (p < 0.001). Specificity was significantly higher using a combination of HE4 and CA125 (99.5%) compared to either HE4 or CA125 alone (90.4% and 91.4%, respectively, p < 0.001). Moreover, the positive likelihood ratio for combination HE4 and CA125 was significantly higher (104.5; 95% CI 13.6–800.0) compared to HE4 alone (5.81; 95% CI 2.83–11.90) or CA125 alone (6.97; 95% CI 3.91–12.41). Conclusions: The combination of HE4 and CA125 represents the best tool to predict the risk of ovarian cancer in patients with a PBOT.

Highlights

Presumed benign ovarian tumours (PBOT) are defined by the International Ovarian Tumour Analysis (IOTA) group, without suspected sonographic criteria of cancer, without ascites or metastasis
To determine the specificity of the association of human epididymis protein 4 (HE4) and cancer antigen 125 (CA125), we considered as abnoSrmpeaclifaicCitAy 1f2o5r CscAor1e25a,bHovEe4,thReMthI raensdhoRldOMofA35wUas/L9a0s.4s%oc,ia91te.4d%w, i9t9h.0a%n HanEd4 8v3a.3lu%e,grreesapteecrtitvhealny 7(S0epemTaobl/lLe iSn2)p. rTeomdeentoeprmauinsaeltphaetsiepnetcsifaicnidty1o4f0thpemaosls/oLciinatipoonstomf eHnEo4paaundsaCl pAa1t2ie5n, tws.e Icfoantsildeaesrtedonaes oafbnthoermtwaloamCaArk12e5rsscwoerreeabbeolvoewththe ethtrhersehsohlodldosf,3t5hUe /rLesauslstowciaastecdownsiitdhearnedHnEo4rvmaalul.eSgpreeacitfiercitthyawn a70s spimgnoilfi/cLainntlpyrheimgheneropuasiunsgalapcaotmiebnitnsaatinodn1o4f0HpEm4oaln/Ld iCnAp1o2s5tm(9e9n.5o%pa) ucosaml ppaarteiednttos.HIfEa4t oleraCstAo1n2e5 oaflotnhee two markers were below the thresholds, the result was considered normal
We find an area under the curve (AUC) for risk of malignancy index (RMI) lower than the area of HE4, the risk of ovarian malignancy index (ROMA) algorithm or the CA125 and HE4 association (0.91, 0.92 and 0.92, respectively) which means that the RMI algorithm is not the best aid tool for the diagnosis of ovarian cancer

Summary

Introduction

Presumed benign ovarian tumours (PBOT) are defined by the International Ovarian Tumour Analysis (IOTA) group, without suspected sonographic criteria of cancer, without ascites or metastasis. The aim is to evaluate the efficacy of human epididymis protein 4 (HE4), cancer antigen 125 (CA125), the risk of malignancy index (RMI) and the risk of ovarian malignancy index (ROMA) to predict ovarian cancer in women with PBOT. The main secondary endpoints were specificity and likelihood ratio of RMI, ROMA and tumours markers. The malignant group had significantly higher mean values of HE4, CA125, RMI and ROMA compared to the benign group (p < 0.001). PBOT is an ovarian tumour (more often a cyst but not always) that is not classified by ultrasound findings as a polycystic ovary nor a malignant or borderline tumour, and whose diagnosis requires complementary explorations (imaging examination, serum markers like Carbohydrate Antigen 125) that must be prioritized in order to propose an adapted management (abstention, monitoring, surgical treatment) [5,6,7]

Objectives

Methods

Results

Discussion

Conclusion