title: Are serum HE4 or ROMA scores useful to experienced examiners for improving characterization of adnexal masses after transvaginal ultrasonography?
abstract: OBJECTIVE
  To determine whether serum human-epididymis protein-4 (HE4) levels or Risk of Ovarian Malignancy Algorithm (ROMA) scores are useful second-stage tests for tumors thought to be difficult to characterize as benign or malignant on the basis of ultrasound findings by experienced examiners, and to investigate whether adding information on serum HE4 levels or ROMA scores to ultrasound findings improves diagnostic performance.
  
  
  METHODS
  This was a prospective cross-sectional diagnostic accuracy study conducted in a tertiary referral center that enrolled consecutive women with a known adnexal mass scheduled for surgery. Experienced level III examiners classified each mass as certainly or probably benign, difficult to classify, or probably or certainly malignant after preoperative ultrasound examination. Serum HE4 and CA 125 levels were measured before surgery.
  
  
  RESULTS
  The final database comprised 360 women, of whom 216 (60%) had benign and 144 (40%) had malignant disease. Examiners were highly confident in 196 cases (54%), moderately confident in 135 (38%) and completely uncertain about their diagnosis in 29 (8%) cases. With a sensitivity of 67% and specificity of 70%, subjective assessment outperformed HE4 and ROMA in the subgroup of difficult tumors. Both tests had low discriminatory capacity with poor areas under the receiver-operating characteristics curve of 0.536 (95% CI, 0.302-0.771) and 0.565 (95% CI, 0.294-0.836), respectively. A strategy that incorporates sequential testing of serum HE4 or ROMA scores after transvaginal ultrasonography resulted in a deterioration in overall test performance.
  
  
  CONCLUSIONS
  Measurement of serum HE4 or calculating scores using the ROMA as secondary tests does not seem useful for classifying adnexal tumors after subjective assessment with transvaginal ultrasonography.
authors.affiliation: KU Leuven Department of Development and Regeneration, Leuven, Belgium; Department of Obstetrics and Gynecology and Leuven Cancer Institute, University Hospitals, KU Leuven, Leuven, Belgium.
authors.forename: J
authors.initials: J
authors.lastname: Kaijser
authors.forename: T
authors.initials: T
authors.lastname: Van Gorp
authors.forename: M-E
authors.initials: ME
authors.lastname: Smet
authors.forename: C
authors.initials: C
authors.lastname: Van Holsbeke
authors.forename: A
authors.initials: A
authors.lastname: Sayasneh
authors.forename: E
authors.initials: E
authors.lastname: Epstein
authors.forename: T
authors.initials: T
authors.lastname: Bourne
authors.forename: I
authors.initials: I
authors.lastname: Vergote
authors.forename: B
authors.initials: B
authors.lastname: Van Calster
authors.forename: D
authors.initials: D
authors.lastname: Timmerman
mesh_terms: D000291:Adnexal Diseases / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D000328:Adult; D000465:Algorithms; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood*; D003430:Cross-Sectional Studies; D003661:Decision Support Techniques; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D011446:Prospective Studies; D011506:Proteins / Q000378:metabolism*; D015203:Reproducibility of Results; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D014463:Ultrasonography; D014621:Vagina; D000081102:WAP Four-Disulfide Core Domain Protein 2
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D011506:Proteins; D000081102:WAP Four-Disulfide Core Domain Protein 2; C569698:WFDC2 protein, human
keywords: CA 125 protein; HE4 protein, human; diagnostic test; ovarian neoplasms; ultrasonography