Hyperthermic intraperitoneal chemotherapy (HIPEC) for primary advanced-stage or recurrent ovarian cancer: A systematic review and meta-analysis of randomized controlled trials.

Abstract

5583 Background: Ovarian cancer is the gynecologic malignancy with the highest mortality rate. Despite cytoreductive surgery (CRS) and adjuvant or neoadjuvant systemic therapy, the rate of peritoneal recurrence remains high. Hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a potential treatment option, delivering high concentrations of heated chemotherapy directly to the tumor site, enhancing local cytotoxicity. Methods: We searched PubMed, Embase, and Cochrane for randomized clinical trials (RCTs) comparing CRS plus HIPEC versus CRS alone. Hazard ratios (HR), odds ratios (OR) and mean differences (MD) were pooled using Review Manager software version 5.4. Heterogeneity was assessed with I 2 statistics. The main outcomes were overall survival (OS), median OS, progression-free survival (PFS), median PFS, operative time in minutes, Grade 3 or higher adverse events, time from surgery to adjuvant chemotherapy and length of hospital stay (LOS) in days. Subgroup analysis was performed for primary and recurrent cancer outcomes. Results: A total of 1,259 patients from 8 RCTs were included, with 636 (50.52%) undergoing CRS with HIPEC. The median follow-up period ranged from 32 to 121.2 months. CRS plus HIPEC significantly improved OS (HR 0.76; 95% CI 0.62-0.93; p = 0.009; I² = 27%), with a significant benefit also observed in the subgroup analyses of primary ovarian cancer (HR 0.66; 95% CI 0.52-0.85; p = 0.001; I² = 0%). However, no significant difference was observed for recurrent ovarian cancer (HR 0.87; 95% CI 0.63-1.19; p = 0.38; I² = 39%). Median OS also significantly favored CRS plus HIPEC (MD 9.99; 95% CI 2.40-17.58; p = 0.01; I² = 0%). PFS was not significantly different between groups (HR 0.74; 95% CI 0.52-1.06; p = 0.10; I² = 76%). In subgroup analysis, PFS was significantly improved for primary ovarian cancer (HR 0.62; 95% CI 0.49-0.79; p = 0.0001; I² = 0%), but not for recurrent ovarian cancer (HR 0.80; 95% CI 0.41-1.56; p = 0.52; I² = 84%). Median PFS showed no statistical difference (MD 1.98; 95% CI -1.20-5.15; p = 0.22; I² = 29%). Time from surgery to adjuvant chemotherapy was not statistically different (MD -0.13; 95% CI -4.49-4.23; p = 0.95; I² = 0%). Operative time was significantly shorter in the control group (MD 127.75; 95% CI 89.61-165.89.; p < 0.00001; I² = 51%), as were LOS (MD 1.49; 95% CI 0.12-2.87; p = 0.03; I² = 0%) and Grade 3-5 adverse events (OR 1.50; 95% CI 1.05-2.16; p = 0.03; I² = 40%). Conclusions: In patients with ovarian cancer, HIPEC significantly improved OS, particularly in the subgroup of primary ovarian cancer. PFS was also significantly improved in this subgroup. However, these benefits were associated with higher rates of adverse events and longer LOS. Our analysis supports the use of HIPEC in the treatment of ovarian cancer, especially for patients with primary ovarian cancer.