5550 Background: Complete resection (CR) at primary debulking surgery is the single most important prognostic factor in AOC. It has been demonstrated, that suboptimal debulking (residual disease > 1cm) might be associated with TCGA molecular subtypes and de novo generated gene expression (GE) signatures. The aim of this study was to validate previous findings and to investigate the impact whole transcriptome GE analyses might have on postoperative residual tumor prediction in a phase III ovarian cancer frontline trial. Methods: Core biopsies from formalin fixed paraffin embedded tumor tissue of FIGO stage IIIC/IV AGO-OVAR 11/ICON7 pts were used to generate whole-genome DASL GE data. TCGA molecular subtype and two previously published GE debulking signatures (7 genes and 11 genes) were correlated with size of residual disease (CR vs. any residual disease). Logistic Regression (LR), support vector machine with polynomial kernel, and random forest were used as classifiers. We built models with all GE features as well as gene selected with HITON-PC, a method that select the markov blanket of the outcome. Results: 283 pts met inclusion criteria, of those 114 (40.3%) had complete resection. Previous reported debulking signatures using 7 and 11 genes respectively did not predict residual disease in this cohort. Best Area under the Curve (AUC) for 7 gene signature was generated using LR 0.50 ± 0.05, while 11 gene signature had an AUC of 0.53 ± 0.04. Similarly, TCGA molecular subtypes (AUC = 0.56 ± 0.04), an independent de novo developed signature (AUC = 0.51 ± 0.04) and the total gene expression data set using all 21,000 genes (AUC = 0.55 ± 0.03) were not able to predict residual disease status. Conclusions: In contrast to previous findings, we were not able to predict residual disease using GE in tumor samples from the AGO-OVAR11/ICON7 phase III trial. A standardized radical surgical approach resulting in a higher frequency of complete resection might allow detection of biologic factors responsible for sub-optimal debulking. The ongoing AGO-OVAR TRUST trial might be able to address this important clinical question.