Comment on “The Role of Hyperthermic Intraperitoneal Chemotherapy in Newly Diagnosed and Recurrent Ovarian Cancer: A Time-to-Event Meta-analysis of Randomized Trials”

Ovarian cancer remains a challenge due to its high mortality rate and high prevalence worldwide. Cytoreductive surgery (CRS) followed by platinum-based chemotherapy is the current standard of treatment for ovarian cancer, with an objective of the achievement of microscopic residual disease. Unfortunately, recurrence rates are still high, thus emphasizing the need for more effective treatment options for recurrent disease. Recently, hyperthermic intraperitoneal chemotherapy (HIPEC) has been put forward as a promising adjunct to CRS for both advanced and recurrent ovarian cancer. Previous studies have shown that adding HIPEC to CRS can significantly prolong recurrence-free and overall survival rates; though this is promising, aspects of the delivery of HIPEC treatment have been inconsistent across studies and institutions. Previous meta-analyses have focused on summary hazard ratios or median survival values rather than time-to-event analyses. This study was designed to address this gap and provide an individual patient data (IPD)-level meta-analysis to evaluate the survival impact of HIPEC on ovarian cancer.

A literature search was conducted using Scopus, PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov through June 2025. Inclusion criteria for studies were those that enrolled patients with newly diagnosed or recurrent ovarian cancer with evidence of peritoneal carcinomatosis, those that compared CRS (primary, interval, or secondary) alone to CRS with HIPEC, and those that reported at least one relevant outcome from the following: overall survival (OS), progression-free survival (PFS), or treatment-related adverse events. Only randomized controlled trials were included in this review and meta-analysis. Risk of bias was assessed using the Cochrane Risk of Bias tool for randomized trials.

Final analysis included 8 publications corresponding to 7 randomized controlled trials. A total of 1300 patients with epithelial ovarian cancer were enrolled, with 653 receiving CRS only and 647 receiving CRS and HIPEC. Of the 1300 patients, 500 had new ovarian cancer diagnoses and 800 had recurrent diagnoses. Three of the 8 trials were at low risk of bias, 4 of them had some risk of bias, and 1 had high risk of bias. Pooled analysis of IPD showed that adding HIPEC to interval CRS significantly improved PFS and OS in newly diagnosed ovarian cancer [hazard ratio (HR) 0.653, 95% CI: 0.517-0.824, P < 0.001 for PFS; HR: 0.667, 95% CI: 0.535-0.855, P = 0.001 for OS]. For recurrent disease, there was a nonsignificant trend toward lower mortality in the combination group versus CRS alone, and these results were confirmed by sensitivity analysis excluding the trial at high risk of bias. PFS was also not significantly affected in recurrent disease.

Subgroup analysis in recurrent disease that stratified by the use of neoadjuvant chemotherapy (NACT) showed that HIPEC was associated with significantly improved survival in those who received NACT (HR: 0.77, 95% CI: 0.60-0.98). This effect was not seen in patients who did not receive NACT. When stratified by HIPEC technique, newly diagnosed patients who received open HIPEC had the highest survival benefit (HR: 0.70, 95% CI: 0.54-0.90), with no significant benefit shown in patients with recurrent disease. In terms of PFS, benefits of HIPEC varied widely based on treatment setting and duration.

Serious toxicity was not significantly higher with HIPEC, though this result had substantial heterogeneity. Other adverse events had problems with heterogeneity as well, with no serious adverse events appearing significant after correction for interactions. The only consistent significant adverse event was acute renal failure, which was increased with HIPEC [risk ratio (RR): 3.36, 95% CI: 1.55-7.30, P = 0.002], which supports the implementation of perioperative renal protection.

These results indicate that HIPEC is most effective at improving survival in the context of newly diagnosed ovarian cancer with NACT. Various subgroup analyses showed that there is little benefit in recurrent ovarian cancer, but significant heterogeneity may be affecting these results. Together, the results of this study support a selective, case-by-case tailored approach to the use of HIPEC in ovarian cancer, with careful consideration of risks and benefits to each individual patient. Future studies should focus on standardizing reporting and methods to improve comparability and generalizability of results. Future research should also aim to optimize outcomes for patients as well as identify the patients who will receive the most significant benefit from this treatment.

(Summarized from Altayf A, Nelson G, Chiva LM, et al. The role of hyperthermic intraperitoneal chemotherapy in newly diagnosed and recurrent ovarian cancer: A time-to-event meta-analysis of randomized trials. Gynecol Oncol . 2026;208:22-31. doi:10.1016/j.ygyno.2026.03.002)