Thrombocytosis and hyperfibrinogenemia are predictive factors of clinical outcomes in high-grade serous ovarian cancer patients

Abstract

Background: Over 20 % of ovarian cancer patients have preoperative thrombocytosis or hyperfibrinogenemia. We aimed to demonstrate the clinical and prognostic significance of thrombocytosis and hyperfibrinogenemia in high-grade serous ovarian cancer (HGSC). Methods: We retrospectively investigated HGSC patients who underwent primary staging or debulking surgery between April 2005 and June 2013 in our institution. None of these patients had received neoadjuvant chemotherapy. Data, including age, performance status, FIGO stage, serum CA125, platelet count, fibrinogen level, and surgical residual disease, were collected. Thrombocytosis was defined as a platelet count greater than 450 × 109/L, and hyperfibrinogenemia was defined as a fibrinogen level higher than 4.00 g/L. Progression-free survival (PFS) and overall survival (OS) were analyzed with the Kaplan-Meier method and log-rank tests for univariate analyses. For the multivariate analyses, Cox regression analysis was used to evaluate the effects of the prognostic factors, which are expressed as hazard ratios (HRs). Results: A total of 875 consecutive HGSC patients were identified. The median follow-up time was 29 (1-115) months. The median (interquartile range, IQR) preoperative platelet count was 301 (235-383) × 109/L, and 121 (13.8 %) women had thrombocytosis. The median (IQR) preoperative fibrinogen level was 3.85 (3.19-4.45) g/L, and 332 (45.9 %) of the patients had hyperfibrinogenemia. Both preoperative thrombocytosis and hyperfibrinogenemia were associated with an advanced FIGO stage (p = 0.008 and <0.001, respectively), an increased CA125 level (p = 0.004 and 0.001, respectively), more extensive ascites (p < 0.001 and <0.001, respectively), more extensive residual disease (p < 0.001 and <0.001, respectively) and chemosensitivity (p = 0.043 and <0.001, respectively). In the univariate analyses, hyperfibrinogenemia was associated with reduced PFS (p < 0.001) and OS (p < 0.001). However, thrombocytosis was not found to be a potential predictor of PFS (P = 0.098) or OS (p = 0.894). In the multivariate analyses, hyperfibrinogenemia was an independent predictor of OS (p = 0.014) but not PFS (p = 0.062). Conclusion: Preoperative thrombocytosis and hyperfibrinogenemia reflected tumor burden to some extent and thus influenced treatment outcomes, and the fibrinogen level was found to be useful as a prognostic predictor in the HGSC patients.