Secondary cytoreductive surgery (S-CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in recurrent ovarian cancer: Current evidence and clinical perspectives

Recurrent epithelial ovarian cancer (rOC) remains a major therapeutic challenge because of its high relapse rate and the progressive development of chemoresistance. Secondary cytoreductive surgery (S-CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been explored as locoregional strategies to overcome the limitations of systemic therapy, but their clinical value varies substantially according to platinum sensitivity, surgical completeness, and patient selection. In platinum-sensitive rOC (PS-rOC), evidence from randomized controlled trials (RCTs) demonstrates that S-CRS provides survival benefit only when completeness of CRS (C-CRS) to CCR0 is achieved in rigorously selected patients using validated selection tools. Meta-analytic data further confirmed that incomplete resection confers little clinical advantage and may fail to offset surgical morbidity. The addition of HIPEC to S-CRS in this setting is supported by a biologically plausible rationale and has been associated with an overall survival (OS) benefit, although no consistent improvement in progression-free survival (PFS) has been demonstrated and treatment-related adverse events (TRAEs), particularly hematologic and renal AEs, are increased. These findings support a selective, center-experienced, and protocol-conscious application of HIPEC rather than routine use. In contrast, high-level evidence supporting S-CRS or S-CRS plus HIPEC in platinum-resistant rOC (PR-rOC) remains lacking. Available data are derived primarily from small retrospective series and systematic reviews with substantial heterogeneity and selection bias, precluding definitive conclusions regarding survival benefit. Several ongoing phase III RCTs are expected to clarify the optimal role, timing, and patient selection for HIPEC-based strategies across different disease settings. Overall, current evidence supports an individualized, biology-driven approach to rOC, integrating surgical feasibility, anticipated systemic treatment efficacy, and careful risk-benefit assessment within a multidisciplinary framework.