Prognostic Factors of Advanced Ovarian Cancer in the Era of HIPEC: A Multicenter Retrospective Study from an ESGO-Certified Center and an ESPSO-Certified Center

<b>Background/Objectives</b>: Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) may modify the prognostic impact of established clinical and surgical factors in advanced ovarian cancer. A retrospective study was conducted to identify independent predictors of survival, recurrence patterns and major postoperative complications in the HIPEC setting. <b>Methods</b>: In total, 265 women with advanced-stage ovarian cancer operated on between 2015 and 2019 were included. Patients were treated with CRS, with or without HIPEC. Patients' characteristics, oncological and follow-up information were collected. <b>Results</b>: In total, 62.3% underwent primary CRS, and 39.2% received HIPEC, with complete or near-complete cytoreduction (CC-0/1) achieved in 85.6%. Major complications (≥grade III) were recorded in 16.6% of the patients. HIPEC, high peritoneal cancer index (PCI), and greater intraoperative blood loss were found to independently increase the odds of major postoperative complications, while prior surgery was the only independent predictor of local-regional recurrence. The median follow-up was 34 months, with a median progression-free (PFS) and overall survival (OS) of 26 and 77 months, respectively. Multivariable analysis identified systematic lymphadenectomy and serous histology as independent predictors for PFS and also for OS, with the addition of CC-3. Survival analysis with Kaplan-Meier curves revealed that CRS plus HIPEC was associated with significantly better OS, but not PFS, compared with CRS alone. <b>Conclusions</b>: Systematic lymphadenectomy, serous histology, and absence of macroscopic gross residual disease emerge as key independent favorable prognostic factors in the HIPEC era, while prior surgery adversely affects loco-regional control. CRS plus HIPEC improved OS in this specific regimen's perfusion protocol but was associated with higher major postoperative complications, underscoring the need for careful patient selection.