The time interval from surgery to start of chemotherapy significantly impacts prognosis in patients with advanced serous ovarian carcinoma - analysis of patient data in the prospective OVCAD study.

OBJECTIVE: Cytoreductive surgery and platinum-based systemic therapy constitute the standard treatment of patients with advanced ovarian cancer. The aim of the present study was to evaluate whether the time interval from surgery to start of chemotherapy has an impact on clinical outcome. METHODS: Data of 191 patients with advanced serous (FIGO III-IV) ovarian cancer from the prospective multicenter study OVCAD (OVarian CAncer Diagnosis) were analyzed. All patients underwent primary surgery followed by platinum-based chemotherapy. RESULTS: The 25%, 50%, and 75% quartiles of intervals from surgery to start of chemotherapy were 22, 28, and 38 days, respectively (range, 4-158 days). Preoperative performance status (P<0.001), extent of surgery (P<0.001), and perioperative complications (P<0.001) correlated with intervals from surgery to initiation of chemotherapy. Timing of cytotoxic treatment [≤ 28 days versus >28 days; hazard ratio (HR) 1.73 (95% confidence interval 1.08-2.78), P=0.022], residual disease [HR 2.95 (95% confidence interval 1.87-4.67), P<0.001], and FIGO stage [HR 2.26 (95% confidence interval 1.41-3.64), P=0.001] were significant prognostic factors for overall survival in multivariate analysis. While the interval from surgery to start of chemotherapy did not possess prognostic significance in patients without postoperative residual disease (n=121), it significantly correlated with overall survival in patients with postoperative residual disease [n=70, HR 2.24 (95% confidence interval 1.08-4.66), P=0.031]. CONCLUSION: Our findings suggest that delayed initiation of chemotherapy might compromise overall survival in patients with advanced serous ovarian cancer, especially when suboptimally debulked.

Preoperative HE4 expression in plasma predicts surgical outcome in primary ovarian cancer patients: results from the OVCAD study.

OBJECTIVES: Epithelial ovarian cancer (EOC) is the major cause of death due to gynecological malignancies. The most important prognostic factors are residual tumor mass after surgery and platinum-response. No predictive biomarkers are available to identify patients who will benefit from standard treatment. The aim of our study was to analyze the role of HE4 in predicting surgical and clinical outcome in primary EOC. METHODS: In the European multicentric project "OVCAD", 275 consecutive patients with primary EOC were enrolled. Patients were eligible if radical cytoreductive surgery was performed and platinum-based chemotherapy was applied. Plasma and ascites samples were collected before or during surgery. The concentrations of HE4 and CA125 was determined using ELISA and Luminex technique, respectively. RESULTS: Median age at first diagnosis was 58 years (range 18-85 years). Most patients presented with advanced stage disease, FIGO III or IV (94.6%), grades II-III (96%) and serous histology (86.2%). In most cases a complete cytoreduction to no residual tumor mass was achieved (68.4%). Higher plasma HE4 levels correlated with poor surgery outcome in terms of macroscopically residual tumor mass (p<0.001) and platinum-resistance (p=0.009). Plasma CA125 and the risk index (HE4 and CA125) were independent predictive factors for surgical outcome (p=0.001, OR=3.37, 95% CI=1.61-7.06 and p<0.001, OR=6,041, 95% CI=2.33-15.65, respectively). FIGO stage III was an independent predictive factor for platinum response (p=0.039, OR=0.436, 95% CI=0.198-0.960). CONCLUSIONS: The presented data are showing that the combination of HE4 and CA125 expression in plasma might predict the surgical outcome in EOC and by this may have a prognostic impact on PFS and OS.