Pre-operative circulating tumor cells predict worse treatment outcome in patients with high-grade serous ovarian cancer

High-grade serous ovarian cancer (HGSOC) is the most lethal gynecological malignancy. Pre- and post-operative, non-invasive biomarkers for reliable treatment outcome prediction, (minimal) residual disease detection, and prognosis are not yet established in clinical practice for these patients. This prospective study quantified circulating tumor cells (CTCs) in 7.5 ml peripheral blood in 56 women with FIGO stages IIIC and IV HGSOC before and after primary cytoreductive surgery and in 9 women with benign ovarian disease. Clinical outcomes were assessed during the median follow-up of 35.4 months. CTCs were detected in 48.2% (27/56) of patients pre-operatively and in 46.4% (26/56) post-operatively, but not in benign controls. Pre-operative CTCs were associated with suboptimal cytoreductive surgery (OR = 15.6, 95% CI: 2.97-127.0, p = 0.0031), worse platinum response (p = 0.0173), lymph node metastases (p = 0.0151), and shorter progression-free (p = 0.0045) and overall survival (p = 0.0241). Post-operative CTC-augmented residual tumor was significantly associated with worse OS (p = 0.047). In multivariable analyses, pre-operative CTCs remained an independent surrogate marker for incomplete debulking, platinum resistance, and poor survival in HGSOC. Therefore, the quantification of CTCs in HGSOC pre- and post-operatively may be used to guide treatment selection, reduce surgical morbidity, improve the healthcare provider's resource allocation and planning, and enhance patient counseling.