Exploring the frontier: promising survival in selected patients after CRS and HIPEC for peritoneal metastases from hepatocellular carcinoma—a systematic review

Hepatocellular carcinoma with peritoneal metastases (HCC-PM) is a rare and aggressive disease with limited therapeutic options and poor prognosis under systemic treatments. Recent evidence suggests that cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) may provide a survival benefit in selected patients. This systematic review aims to assess the effectiveness and safety of CRS + HIPEC in the management of HCC-PM. This study was conducted according to PRISMA guidelines and registered in PROSPERO(CRD42024627130). We systematically searched MEDLINE, Web of Science, and Scopus up to December 17, 2024. Eligible studies included adults with HCC-PM treated with CRS + HIPEC, reporting outcomes on postoperative complications, overall survival (OS), and disease-free survival (DFS). Risk of bias was assessed using the Newcastle-Ottawa Scale. Six retrospective studies, encompassing 57 patients, were included. Peritoneal Cancer Index (PCI) ranged from 2 to 35. The most used HIPEC agents were mitomycin-C and cisplatin, although none are standard systemic therapies for HCC. Major postoperative complications ranged from 16.6 to 47.6%. No intraoperative deaths were reported, but one perioperative death occurred in a patient with high PCI and incomplete cytoreduction. Median OS ranged from 15.7 to 49.9 months, while DFS ranged from 5.0 to 26.3 months. Lower PCI, complete cytoreduction (CCR-0/1), preserved liver function and good performance status were associated with improved outcomes. CRS + HIPEC appears to be a feasible therapeutic option for selected HCC-PM patients, potentially offering superior survival outcomes compared to systemic therapy alone. However, high morbidity rates, recurrence risk, and heterogeneous protocols highlight the need for standardized approaches and prospective clinical trials to define its role in this population.