HE4, CA125 and risk of ovarian malignancy algorithm (ROMA) as diagnostic tools for ovarian cancer in patients with a pelvic mass: An Italian multicenter study

Gynecol Oncol. 2016 May;141(2):303-311. doi: 10.1016/j.ygyno.2016.01.016. Epub 2016 Jan 19.

Abstract

Objective: This multicenter study aims to evaluate HE4, CA125 and risk of ovarian malignancy algorithm (ROMA) performance in the differential diagnosis of epithelial ovarian cancer (EOC).

Methods: A total of 405 patients referred to gynecological oncologist with suspicious pelvic mass requiring a surgery for identification of EOC were consecutively enrolled; 387 patients satisfied inclusion criteria: 290 benign diseases; 15 borderline neoplasia and 82 tumors (73 EOC).

Results: Good diagnostic performance in discriminating benign from EOC patients was obtained for CA125, HE4 and ROMA when calculating optimal cut-off values: premenopause, specificity (SP) >86.6, sensitivity (SN) >82.6, area under the curves (AUC)≥0.894; postmenopause, SP>93.2, SN>82, AUC≥0.928. Fixing SP at 98%, performance indicators obtained for benign vs EOC patients were: premenopause, SN:65.2%, positive predictive value (+PV): 75%, positive likelihood ratio (+LR): 26.4 for CA125; SN:69.6%, +PV:76.2%, +LR:28.1 for HE4; SN:69.6%, +PV: 80%; +LR:35.1 for ROMA; postmenopause, SN:88%, +PV: 95.7%, +LR:38.7 for CA125; SN:78%, +PV:95.1%, +LR:34.3 for HE4; SN:88%, +PV:97.8%, +LR:77.4 for ROMA. When using routine cut-off thresholds, ROMA showed better well-balanced values of both SP and SN (premenopause, SN:87%, SP:86.1%; postmenopause, SN:90%; SP:94.3%).

Conclusions: Overall, ROMA showed well balanced diagnostic performance to differentiate EOC from benign diseases. Meaningful differences of +PVs and +LRs between HE4 and CA125 suggest that the two markers may play at least in part different roles in EOC diagnosis, with HE4 seeming to be more efficient than CA125 in ruling in EOC patients in the disease group, also in early stages tumors, both in pre and postmenopause.

Keywords: CA125; Epithelial ovarian cancer; HE4; Pelvic mass; ROMA; Tumor markers.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adult
  • Algorithms
  • CA-125 Antigen / blood*
  • Carcinoma, Ovarian Epithelial
  • Diagnosis, Differential
  • Female
  • Humans
  • Immunoassay
  • Membrane Proteins / blood*
  • Neoplasm Staging
  • Neoplasms, Glandular and Epithelial / blood*
  • Neoplasms, Glandular and Epithelial / diagnosis*
  • Neoplasms, Glandular and Epithelial / pathology
  • Neoplasms, Glandular and Epithelial / surgery
  • Ovarian Neoplasms / blood*
  • Ovarian Neoplasms / diagnosis*
  • Ovarian Neoplasms / pathology
  • Ovarian Neoplasms / surgery
  • Proteins / metabolism*
  • Risk Factors
  • 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