Objective There are no current guidelines regarding evaluation of patients with normal CA125 at initial diagnosis during routine surveillance after completion of treatment. Thus, the purpose of this study was to evaluate the role of human epididymis protein 4 (HE4) in the detection of recurrence in patients with ovarian cancer and a negative CA125 at diagnosis.

Methods All patients with ovarian cancer with a negative CA125 referred to the Division of Gynecologic Oncology of the University Campus Bio-Medico of Rome were included in the study. Inclusion criteria were: age between 18 and 70 years old, diagnosis of epithelial ovarian cancer, optimal primary surgery (residual tumor <1 cm), and normal CA125 at initial diagnosis. Patients with other malignancies or chronic diseases were excluded from the study. Statistical analysis was based on the calculation of percentages, means, medians, and ranges of the values.

Results A total of eight patients were included in the study. The median age was 53 years (range 40–75). All patients had a normal CA125 at initial diagnosis while seven (87.5%) patients had abnormal HE4 levels at diagnosis. The International Federation of Gynecology and Obstetrics (FIGO) stages at enrollment varied from IC to IIIC (IB (1), IC (3), IIC (1), IIIC (3)). The most common histologic subtype was serous (62.5%). Seven patients recurred and had abnormal HE4 and normal CA125 values. The median HE4 at recurrence was 107 pmol/L. The median disease-free interval was 55 months (range 5–108) and all the patients underwent optimal cytoreductive surgery.

Conclusions HE4 levels may serve as a marker for recurrence in patients with a normal CA125 at initial diagnosis. Future studies are needed to evaluate the role of HE4 levels in earlier detection of recurrent ovarian cancer.