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The Role of HE4, a Novel Biomarker, in Predicting Optimal Cytoreduction After Neoadjuvant Chemotherapy in Advanced Ovarian Cancer
  1. Francesco Plotti*,
  2. Giuseppe Scaletta*,
  3. Stella Capriglione*,
  4. Roberto Montera*,,
  5. Daniela Luvero*,
  6. Salvatore Lopez*,
  7. Alessandra Gatti*,
  8. Carlo De Cicco Nardone*,
  9. Corrado Terranova* and
  10. Roberto Angioli*
  1. * Department of Obstetrics and Gynaecology, Campus Bio-Medico University of Rome, Rome; and
  2. Unit of Obstetrics and Gynecology, Magna Graecia University of Catanzaro, Catanzaro, Italy.
  1. Address correspondence and reprint requests to Stella Capriglione, MD, Department of Obstetrics and Gynecology, Campus Bio-Medico University of Rome, Via Alvaro del Portillo, 200-00128 Rome, Italy. E-mail: s.capriglione{at}


Objectives This study aimed to evaluate serum human epididymis protein 4 (HE4) changes during neoadjuvant chemotherapy (NACT) to establish HE4 predebulking surgery cutoff values and to demonstrate that CA125, HE4, and computed tomography (CT) taken together are better able to predict complete cytoreduction after NACT in advanced ovarian cancer patients.

Methods From January 2006 to November 2015, patients affected by epithelial advanced ovarian cancer (International Federation of Gynecology and Obstetrics stage III–IV), considered not optimally resectable, were included in this prospective study. After 3 cycles of NACT, all patients underwent debulking surgery and were allocated, according to residual tumor (RT), into group A (RT = 0) and group B (RT > 0). Serum CA125, HE4, and CT images were recorded during NACT and compared singularly and with each other in term of accuracy, sensitivity, specificity, and positive and negative predictive value.

Results A total of 94 and 20 patients were included in group A and group B, respectively. The HE4 values recorded before debulking surgery correlated with RT. The identified HE4 cutoff value of 226 pmol/L after NACT was able to classify patients at high or low risk of suboptimal surgery, with a sensitivity of 75% and a specificity of 85% (positive predictive value, 0.87; negative predictive value, 0.70). The combination of CA125, HE4, and CT imaging resulted in the best combination with a sensitivity of 96% and a specificity of 92% (positive predictive value, 0.96; negative predictive value, 0.94).

Conclusions The novel biomarker HE4, in addition to CA125 and CT, is better able to predict the RT at debulking surgery and the prognosis of patients.

  • Neoadjuvant chemotherapy
  • HE4
  • Ovarian cancer
  • Optimal cytoreduction

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  • The authors declare no conflicts of interest.