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Abstract Ovarian cancer is the 5th leading cause of death for women with cancer worldwide. In more than 70% of cases, it is only diagnosed at an advanced stage. Our study aims to give an update on the biological markers for diagnosing ovarian cancer, specifically HE4, CA 125, RMI and ROMA algorithms. Serum CA125 assay has low sensitivity in the early stages and can be increased in certain conditions such as menstruation or endometriosis. The level of HE4 is overexpressed in ovarian tumors. Its specificity is 94% and its level is not affected by endometriosis cysts. The combined measures of CA125 and HE4 have proved to be highly efficient with an area under the curve (AUC) of up to 0.96. Furthermore, this combined measure of CA125 can correct the variations in HE4 which are due to smoking or contraception combining estrogen plus progestin. While the specificity of RMI sometimes reaches 92%, the rather low AUC of 0.86 does not make it the best diagnostic tool. The specificity of ROMA is lower than HE4 (84% compared to 94%). To date, the most efficient biological diagnostic tool to diagnose ovarian cancer is the combination of CA125 and HE4.

Introduction: Our primary objective was to test the hypothesis that human epididymal protein 4 (HE4) and risk of ovarian malignancy index outperform the CA 125 and risk of malignancy index tests in categorizing a pelvic mass into high or low risk of malignancy in a Swedish population. Furthermore, cut-off values needed to be defined for HE4 and ROMA in premenopausal and postmenopausal women prior to their introduction to clinical practice. A third objective was to investigate the correlation between HE4 levels in serum and urine.Material and Methods: Women with a pelvic mass scheduled for surgery were recruited from nine hospitals in south-east Sweden. Preoperative blood samples were taken for analyzing CA125 and HE4 as well as urine samples for analyzing HE4.Results: We enrolled a total of 901 women, of whom 784 were evaluable. In the premenopausal and postmenopausal groups, no significant differences were found for sensitivity, positive and negative predictive value, either for RMI vs ROMA or for CA125 vs HE4 using a fixed specificity of 75%. Cut-off values indicating malignancy were established for HE4 and ROMA in premenopausal and postmenopausal women. We found no correlation between HE4 concentration in serum and urine.Conclusions: We could not confirm that ROMA had diagnostic superiority over RMI in categorizing women with a pelvic mass into low-risk or high-risk groups for malignancy in a Swedish population. We have defined cut-off values for HE4 and ROMA. The lack of correlation between serum and urine HE4 obviates the introduction of urine HE4 analysis in clinical diagnostics. [ABSTRACT FROM AUTHOR]

Background: Distinguishing between malignant and benign ovarian masses is necessary to refer patients to centers with experience in the surgical. Objectives: The aim of this study was to analyze the diagnostic value of the tumor markers, including risk of malignancy index (RMI), human epididymis protein 4 (HE4), cancer antigen125 (CA125), and risk of ovarian malignancy algorithm (ROMA) in ovarian mass. Methods: One hundred patients with ovarian masses were assessed for the tumor markers ROMA, HE4, RMI, and CA125. The sensitivity and specificity of each parameter were calculated, using receiver-operating characteristic curves (ROCs) according to the area under the curve (AUC) for each method. Results: The median CA125, HE4, RMI, and ROMA serum levels had significant difference between malignant and benign masses in the overall assessment (P < 0.001). The AUCs were 0.83 (CA125), 0.88 (HE4), 0.85 (RMI), and 0.92 (ROMA) for benign vs. malignant masses in all the patients. The comparison of ROC curves was carried out, using a pairwise comparison method, and no differences were found among 4 methods. Conclusions: The results based on the AUC markers of CA125, HE4, RMI, and ROMA revealed that the accuracy trend of ROMA was higher than that of CA125, HE4, and RMI in all the patients and each group of pre- and post-menopausal patients. [ABSTRACT FROM AUTHOR]

Context: Pelvic masses are a prevalent cause for referral to gynecologic oncology departments to evaluate the possibility of benign or malignant conditions. Pelvic mass often was found in pelvic examinations among females with ovarian. Tumor markers are advantageous biomarker in tumor diagnosis. Evidence Acquisition: We performed a computerized search in Medline/PubMed databases and Google Scholar with key words: "Cancer antigen 125 (CA125), Human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm(ROMA), Risk of malignancy index (RMI), and Pelvic mass". Results: The usage of tumor marker CA125 alone is associated with serious limitations like low sensitivity for early or stage I dis- ease and lack of specificity especially in pre-menopausal women. Serum HE4 is a good biomarker for discriminating ovarian cancer from benign pelvic disease, but could be affected by several factors including pregnancy, age, and smoking. ROMA has a high sensitivity, specificity, and negative predictive value to predict the presence of ovarian cancer in women with a pelvic mass. RMI could differentiate between benign and malignant pelvic masses, but RMI expression was higher in women with 55 years or more. Conclusions: According to the results of this study, combination of these biomarkers or at least 2 or 3 biomarkers are suggested for early stage diagnosis of pelvic mass with high sensitivity and specificity. [ABSTRACT FROM AUTHOR]

Abstract Objective To validate, in a multicenter clinical trial, the performance of biomarkers and algorithms for differential diagnosis in a population of women diagnosed with an unknown ovarian cyst or pelvic tumor. Methods Six hospitals in Western Sweden consecutively enrolled 638 women from September 2013 to February 2016. Serum, transvaginal ultrasound data, and basic patient characteristics were collected preoperatively. Biomarker levels, risk of malignancy algorithm (ROMA), and risk of malignancy index (RMI) were calculated and compared with the final pathology report. Results Our sample of 638 patients had 445 benign, 31 borderline, and 162 malignant tumors recorded, and the overall incidence of epithelial ovarian cancer was 21%. In postmenopausal women, RMI (>200), ROMA (≥29.9), CA125 (>35 U/mL), and HE4 (>140 pmol/L) showed sensitivity at 89%, 91%, 92%, and 72%, respectively, and specificity at 80%, 77%, 80%, and 92%. In premenopausal women, sensitivity of RMI, ROMA (≥11.6), CA125, and HE4 (>70 pmol/L) was 87%, 87%, 96%, and 83%, respectively, and specificity was 90%, 81%, 60%, 91%. Diagnostic accuracy (ROC AUC) of RMI and ROMA in postmenopausal women was 0.85 and 0.84, and in premenopausal women, 0.90 and 0.81. Conclusion Our results suggest that CA125 is superior to HE4 as a biomarker to identify women with ovarian cancer. HE4 more correctly identifies benign lesions, which may help in differential diagnoses to guide the level of care and decrease overtreatment. This study confirms prior results from single-center studies and suggests the implementation of HE4 measurement in daily practice. Highlights • At recommended cut-off, CA125 outperforms HE4 in correctly diagnosing EOC. • At recommended cut-off, HE4 increases specificity and detects the benign cases. • At recommended cut-offs, the algorithms RMI and ROMA are equally good for triage. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the most lethal gynecologic cancer. Pre-diagnostic testing lacks sensitivity and specificity, and surgery is often the only way to secure the diagnosis. Exploring new biomarkers is of great importance, but the rationale of combining validated well-established biomarkers and algorithms could be a more effective way forward. We hypothesized that we can improve differential diagnostics and reduce false positives by combining (a) risk of malignancy index (RMI) with serum HE4, (b) risk of ovarian malignancy algorithm (ROMA) with a transvaginal ultrasound score or (c) adding HE4 to CA125 in a simple algorithm. With logistic regression modeling, new algorithms were explored and validated using leave-one-out cross validation. The analyses were performed in an existing cohort prospectively collected prior to surgery, 2013–2016. A total of 445 benign tumors and 135 ovarian cancers were included. All presented models improved specificity at cut-off compared to the original algorithm, and goodness of fit was significant (p < 0.001). Our findings confirm that HE4 is a marker that improves specificity without hampering sensitivity or diagnostic accuracy in adnexal tumors. We provide in this study "easy-to-use" algorithms that could aid in the triage of women to the most appropriate level of care when presenting with an unknown ovarian cyst or suspicious ovarian cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the 5th leading cause of death for women with cancer worldwide. In more than 70% of cases, it is only diagnosed at an advanced stage. Our study aims to give an update on the biological markers for diagnosing ovarian cancer, specifically HE4, CA 125, RMI and ROMA algorithms. Serum CA125 assay has low sensitivity in the early stages and can be increased in certain conditions such as menstruation or endometriosis. The level of HE4 is overexpressed in ovarian tumors. Its specificity is 94% and its level is not affected by endometriosis cysts. The combined measures of CA125 and HE4 have proved to be highly efficient with an area under the curve (AUC) of up to 0.96. Furthermore, this combined measure of CA125 can correct the variations in HE4 which are due to smoking or contraception combining estrogen plus progestin. While the specificity of RMI sometimes reaches 92%, the rather low AUC of 0.86 does not make it the best diagnostic tool. The specificity of ROMA is lower than HE4 (84% compared to 94%). To date, the most efficient biological diagnostic tool to diagnose ovarian cancer is the combination of CA125 and HE4. [ABSTRACT FROM AUTHOR]