Resection combined with hyperthermic intraperitoneal chemotherapy in the treatment of spontaneously ruptured hepatocellular carcinoma: a multicenter retrospective study

Background: Spontaneous tumor rupture is a unique and life-threatening presentation of hepatocellular carcinoma (HCC). The optimal postoperative management of patients with spontaneously ruptured HCC (srHCC) remains controversial. Hyperthermic intraperitoneal chemotherapy (HIPEC) has been proposed to reduce peritoneal dissemination, but its clinical benefit in srHCC is uncertain. Objectives: This study aimed to evaluate the survival benefit and safety of postoperative HIPEC combined with hepatic resection in patients with srHCC. Design: A retrospective multicenter cohort study was conducted, including patients with srHCC who underwent curative hepatectomy with or without postoperative HIPEC between 2018 and 2024. Methods: A total of 208 srHCC patients from 4 institutions were enrolled and categorized into the resection group (R) and the resection plus HIPEC group (R-HIPEC). Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were applied to minimize baseline differences. The primary endpoint was recurrence-free survival (RFS), and the secondary endpoint was overall survival (OS). Survival outcomes were assessed using Kaplan–Meier analysis, Cox proportional hazards models, and subgroup analysis. Results: Across the primary, PSM, and IPTW cohorts, patients in the R-HIPEC group achieved significantly longer median RFS (mRFS) and OS than those in the R group. The median OS was 45.6 versus 26.4 months in the primary cohort ( p = 0.025), 48.2 versus 26.4 months in the PSM cohort ( p = 0.025), and 42.9 versus 26.5 months in the IPTW cohort ( p = 0.012). The mRFS was 15.5 versus 7.7 months ( p = 0.002), 18.2 versus 8.3 months ( p = 0.002), and 14.7 versus 7.4 months ( p = 0.014), respectively. Subgroup analysis indicated that patients with Barcelona Clinic Liver Cancer stage 0/A derived significantly greater RFS benefit from HIPEC than those with stage B/C (interaction p = 0.0264). For OS, a significant interaction was observed with postoperative immunotherapy (interaction p = 0.0054). The R-HIPEC group showed a lower incidence of peritoneal implantation metastasis, without an increase in perioperative complications. Conclusion: HIPEC combined with resection for srHCC can effectively prolong survival time. Resection combined with HIPEC and targeted therapy may be a promising strategy for srHCC.