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

Ovarian cancer has the highest mortality among gynecologic malignancies. Despite cytoreductive surgery (CRS) and systemic therapy, peritoneal recurrence remains common. Hyperthermic intraperitoneal chemotherapy (HIPEC) delivers heated chemotherapy directly to the peritoneal cavity, enhancing local cytotoxicity and offering a potential therapeutic strategy. We searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) comparing CRS plus HIPEC versus CRS alone. Hazard ratios (HR), odds ratios (OR), and mean differences (MD) were pooled using Review Manager 5.4. Heterogeneity was assessed using I statistics. Primary outcomes were overall survival (OS) and progression-free survival (PFS); secondary outcomes included operative time, Grade 3-5 adverse events, time to adjuvant chemotherapy, and hospital length of stay (LOS). Subgroup analyses were performed for primary vs. recurrent cancer, neoadjuvant chemotherapy (NACT) vs. no NACT, HIPEC duration (60 vs. 90 min), and high-grade serous vs. other histologies. Eight RCTs (1259 patients) were included; 636 (50.52%) received CRS with HIPEC. HIPEC significantly improved OS (HR 0.79; 95% CI 0.67-0.94; p = 0.006; I = 9%), especially in primary ovarian cancer (HR 0.75; 95% CI 0.60-0.94; p = 0.01; I = 0%). No OS benefit was observed in recurrent disease (HR 0.87; 95% CI 0.63-1.19; p = 0.38; I = 39%). PFS showed no overall difference (HR 0.86; p = 0.30). HIPEC increased operative time (MD 127.75 min; p < 0.00001), LOS (MD 1.49 days; p = 0.03), and Grade 3-5 adverse events (OR 1.50; p = 0.03). In ovarian cancer, HIPEC significantly improved OS, especially in primary disease and following NACT. However, increased morbidity was observed. Further studies should refine patient selection and optimize protocols.