Use of HE4 and CA125 to predict surgical outcome and for prognostic value for progression-free survival (PFS) and overall survival (OS) in primary epithelial ovarian cancer (EOC) patients (pts).

Abstract

5034 Background: Optimal surgical cytoreduction and response to platinum (P) based chemotherapy (ChTh) remain the cornerstones of therapeutic management of primary EOC. Aim of this study was to analyze the predictive role of HE4 and CA125 as biomarkers (BM) for clinical outcome in primary EOC pts at diagnosis and during subsequent follow-up. Methods: In the European OVCAD project 275 pts with primary EOC were enrolled. Pts were eligible if radical cytoreductive surgery and P-based ChTh were applied. Plasma collected at first diagnosis and 6 months after 1st line ChTh in P-sensitive pts was analyzed for HE4 and CA125 levels using ELISA and Luminex technique, respectively. Results: Complete cytoreduction with no residual tumor disease (RTD) was obtained in 69.9% pts. HE4 and CA125 expression in plasma at first diagnosis correlated with RTD, p = 0.002 and p=0.002, respectively. The sensitivity (SE) and specificity (SP) of the combinative use of both BM in predicting RTD was 64.8% and 73.5%, respectively. Pts having over-expression of both BM in plasma had a 6.1 greater risk for RTD (p<0.001, OR: 6.107, 95% CI 2.41-15.46). P-resistance occurred more frequently when both BM were over-expressed (p=0.028, OR= 3.1, 95%CI 1.13-8.46). Elevated BM levels during follow-up predicted recurrence (SE 90% and SP 71% for CA125 ≥55U/ml; SE 72.7% and SP 81.4% for HE4 ≥150pM) and when HE4 or CA125 were positive, a SE of 86.4% and SP of 72.9% were achieved. Elevated CA125 and HE4 at 6 months following adjuvant therapy was associated with significantly poorer PFS (p<0.001, HR 9.6, 95%CI 3.93-23.44 with elevated HE4 or CA125, and HR=50.52, 95%CI 14.44-176.78, with elevated HE4 and CA125) and OS (p<0.001, HR=7.42 95%CI 1.43-38.42 with elevated HE4 or CA125 and HR=28.38 95%CI 6.50-123.97 with elevated HE4 and CA125). Conclusions: The combinative use of HE4 and CA125 appears to have a significant value in predicting optimal surgical outcome and development of P resistance disease in EOC pts. Elevated plasma levels 6 months after 1st line ChTh significantly correlate with OS and PFS in P-sensitive pts.