Common methods used in the preoperative risk of malignancy assessment in patients with an ovarian mass perform suboptimal, leading to incorrect (non-)referral of patients to a specialized center. Serum biomarker human epididymis protein 4 (HE4) is considered as an alternative for the common used biomarker Cancer Antigen 125 (CA125). We observed that current literature on HE4 for this purpose was not performed in a population from general centers and therefore not reflecting the second line population in which a risk of malignancy assessment is relevant. In our study in a second-line population, we observed that HE4 was more cost-effective compared to common methods for the risk of malignancy assessment in patients with an ovarian mass from a second-line population. Additionally, circulating tumor DNA seemed to perform better compared to common methods as well. Besides the use of biomarkers in patients with an ovarian mass, we also investigated their usefulness in predicting surgical outcome in patients with advanced-stage ovarian cancer who have an indication for cytoreductive surgery. We observed that HE4 as part of a non-invasive model predicted well the successful surgery (less than 1 cm residual disease) in patients who underwent interval cytoreductive surgery. Diagnostic laparoscopy can also be considered as an invasive ‘’biomarker’’. Although a randomized controlled trial showed that the diagnostic laparoscopy can be useful in guiding primary treatment in patients with advanced-stage ovarian cancer, we observed that Dutch gynecologic-oncologists do not support routine implementation in clinical practice. Main reasons were centralization of care leading to a better preoperative selection and the availability of non-invasive alternative diagnostics
