Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for the management of primary advanced and recurrent ovarian cancer: a systematic review and meta-analysis of randomized trials

Introduction: Ovarian cancer is the most lethal gynecologic malignancy. Although treatment with hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results, its role remains elusive. Aim: To assess the comprehensive randomized evidence for the use vs non-use of HIPEC in primary (POC) and recurrent (ROC) ovarian cancer. Materials and Methods: The Medline, Embase and Cochrane databases, as well as the ESMO and ASCO conference abstracts of the last 5 years, were scrutinized in January 2022 for randomized controlled trials (RCTs) that studied the use of HIPEC in ovarian cancer. Overall survival (OS), disease- and progression-free survival (DFS/PFS), as well as postoperative morbidity were the outcomes of interest. This study was reported in accordance to the PRISMA reporting guideline. Results: Six RCTs that randomized 737 patients were included in our analysis, of these four studies (519 patients) pertained primary and two (218 patients) recurrent settings. In primary ovarian cancer, the combination of HIPEC with interval cytoreductive surgery (CRS) and neoadjuvant chemotherapy significantly improved the 5-year OS (393 patients, RR=0.77; 95%CI: 0.67-0.90; p-value=0.001) and DFS (HR=0.60; 95%CI: 0.41-0.87; p-value=0.008) compared with standard treatment alone. In the absence of neoadjuvant chemotherapy the use of HIPEC+CRS was not associated to any survival advantage (126 patients, 4-year OS, RR=0.93; 95% CI: 0.57-1.53; p-value=0.781), but the sample size was smaller in this subset. Use of HIPEC in recurrent ovarian cancer did not provide any survival advantage (5-years OS: 218 patients, RR=0.85; 95% CI= 0.45-1.62; p-value=0.626). The risk for grade≥3 adverse events was similar between HIPEC and no HIPEC (RR=1.08; 95%CI: 0.98-1.18; p-value=0.109). Conclusion: In primary ovarian cancer the combination of HIPEC with interval cytoreductive surgery and neoadjuvant chemotherapy is a safe option that significantly improved 5-year OS and DFS. Its use in other settings should continue to be considered investigational