Objectives: We sought to determine the joint predictive value of tumor molecular subtype and CT imaging data in predicting surgical outcomes prior to primary debulking surgery (PDS) in Stage IIIC/IV high-grade serous ovarian cancer patients. Methods: Patients undergoing PDS for Stage IIIC/IV were included. Based on CT imaging, a continuous CT-score indicative of overall disease burden was defined based on six CT measurements of anatomic involvement: (1) diaphragm disease; (2) gastrohepatic/porta hepatis; (3) root of superior mesenteric artery; (4) presence of moderate to severe ascites; (5) intrahepatic lesion, and (6) diffuse peritoneal thickening > 4mm. Patients were then classified as CT-low or CT-high if their score was ≤2 or ≥3, respectively. Molecular subtypes were derived from mRNA profiling of chemo-naïve tumors; women were classified as having mesenchymal (MES) subtype or non-MES subtype tumors. Patients were classified as having no gross residual disease (RD0) or any gross residual disease less than 1 cm (RD1), or gross residual disease greater than 1 cm (RD2). Multivariate regression models were fit to predict RD. The four cohorts, (i) non-MES & CT-low, (ii) non-MES & CT-high, (iii) MES & CT-low, and (iv) MES & CT-high, were compared with Fisher’s exact tests to examine the association with RD and surgical complexity. Graphical Abstract View Large Image Figure Viewer Download Hi-res image Conclusions: Preoperative CT imaging combined with tumor molecular subtyping can identify a subset of women for whom successful primary surgery is unlikely. Preoperative tumor sampling may be useful in advanced OC to better triage these cases to alternative approaches. Objectives: We sought to determine the joint predictive value of tumor molecular subtype and CT imaging data in predicting surgical outcomes prior to primary debulking surgery (PDS) in Stage IIIC/IV high-grade serous ovarian cancer patients. Methods: Patients undergoing PDS for Stage IIIC/IV were included. Based on CT imaging, a continuous CT-score indicative of overall disease burden was defined based on six CT measurements of anatomic involvement: (1) diaphragm disease; (2) gastrohepatic/porta hepatis; (3) root of superior mesenteric artery; (4) presence of moderate to severe ascites; (5) intrahepatic lesion, and (6) diffuse peritoneal thickening > 4mm. Patients were then classified as CT-low or CT-high if their score was ≤2 or ≥3, respectively. Molecular subtypes were derived from mRNA profiling of chemo-naïve tumors; women were classified as having mesenchymal (MES) subtype or non-MES subtype tumors. Patients were classified as having no gross residual disease (RD0) or any gross residual disease less than 1 cm (RD1), or gross residual disease greater than 1 cm (RD2). Multivariate regression models were fit to predict RD. The four cohorts, (i) non-MES & CT-low, (ii) non-MES & CT-high, (iii) MES & CT-low, and (iv) MES & CT-high, were compared with Fisher’s exact tests to examine the association with RD and surgical complexity. Conclusions: Preoperative CT imaging combined with tumor molecular subtyping can identify a subset of women for whom successful primary surgery is unlikely. Preoperative tumor sampling may be useful in advanced OC to better triage these cases to alternative approaches.