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.

Plain language summary

Surgery combined with heated chemotherapy inside the abdomen may improve survival for people with ruptured hepatocellular carcinoma

Background:

Spontaneous rupture of hepatocellular carcinoma (HCC) is rare but life-threatening. The optimal post-surgical management is unclear. Hyperthermic intraperitoneal chemotherapy (HIPEC), which delivers heated chemotherapy into the abdomen during surgery, may help prevent cancer spread, but its benefit in ruptured HCC is uncertain.

Objective:

To assess whether adding HIPEC to surgery improves survival and is safe in patients with ruptured HCC.

Design:

This multicenter retrospective study (four centers, 2018–2024) included 208 patients who underwent surgery for ruptured HCC. Patients received either surgery alone or surgery plus HIPEC. Survival outcomes were compared between groups.

Methods:

Patients were divided into a resection-only group (R) and a resection plus HIPEC group (R-HIPEC). Statistical methods were used to balance baseline characteristics. Recurrence-free survival (RFS) and overall survival (OS) were analyzed.

Results:

Patients in the R-HIPEC group had significantly better outcomes. Median OS was 45.6 months with HIPEC versus 26.4 months without it; median RFS was 15.5 versus 7.7 months. These advantages persisted after adjustment. Subgroup analysis showed greater RFS benefit from HIPEC in early-stage HCC (BCLC 0/A) than in more advanced stages (B/C). HIPEC also appeared to lower the risk of intraperitoneal spread without increasing perioperative complications.

Conclusion:

Adding HIPEC to surgery for ruptured HCC improves survival without increasing complications. Combined with targeted therapy, it may be a promising treatment strategy for these patients.