A multicenter clinical trial validating the performance of HE4, CA125, risk of ovarian malignancy algorithm and risk of malignancy index

Gynecol Oncol. 2018 Oct;151(1):159-165. doi: 10.1016/j.ygyno.2018.08.025. Epub 2018 Aug 24.

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.

Keywords: CA125; HE4; Multicenter study; Ovarian cancer diagnostics; RMI; ROMA.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Algorithms
  • CA-125 Antigen / blood*
  • Carcinoma, Ovarian Epithelial
  • Diagnosis, Differential
  • Female
  • Humans
  • Incidence
  • Membrane Proteins / blood*
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / blood
  • Neoplasms, Glandular and Epithelial / diagnosis*
  • Neoplasms, Glandular and Epithelial / epidemiology
  • Neoplasms, Glandular and Epithelial / pathology
  • Ovarian Cysts / blood
  • Ovarian Cysts / diagnosis*
  • Ovarian Cysts / pathology
  • Ovarian Cysts / surgery
  • Ovarian Neoplasms / blood
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / epidemiology
  • Ovarian Neoplasms / pathology
  • Ovary / pathology
  • Ovary / surgery
  • Pelvic Neoplasms / blood
  • Pelvic Neoplasms / diagnosis*
  • Pelvic Neoplasms / pathology
  • Pelvic Neoplasms / surgery
  • Proteins / analysis*
  • Risk Assessment
  • Sensitivity and Specificity
  • Sweden / epidemiology
  • WAP Four-Disulfide Core Domain Protein 2

Substances

  • CA-125 Antigen
  • MUC16 protein, human
  • Membrane Proteins
  • Proteins
  • WAP Four-Disulfide Core Domain Protein 2
  • WFDC2 protein, human