Adjuvant HAI Oxaliplatin Improves Liver Control After CRLM Surgery : J Clin Oncol | May 2026

Introduction

Recurrence after curative-intent surgery for Colorectal Liver Metastases remains common, particularly in patients with high metastatic burden. The liver represents the dominant site of relapse, even after modern systemic chemotherapy and complete resection or ablation. Hepatic Arterial Infusion allows selective administration of high-dose chemotherapy directly to hepatic tumors while limiting systemic exposure and has shown promising activity in metastatic colorectal cancer. However, prospective randomized data evaluating adjuvant HAI after resection of extensive CRLM have been limited.

Problem Statement

Patients undergoing surgery for four or more colorectal liver metastases remain at extremely high risk for hepatic recurrence despite perioperative systemic chemotherapy. Whether postoperative HAI chemotherapy can improve hepatic disease control and survival outcomes compared with standard intravenous chemotherapy alone has remained uncertain.

Summary

This randomized phase II trial evaluated adjuvant hepatic arterial infusion of oxaliplatin combined with systemic LV5FU2 following curative-intent surgery or ablation of at least four colorectal liver metastases. Ninety-nine high-risk patients previously treated with preoperative systemic chemotherapy were randomized to receive oxaliplatin via hepatic arterial infusion or standard intravenous administration, both combined with intravenous fluorouracil/leucovorin.

After nearly five years of median follow-up, hepatic arterial infusion significantly improved hepatic recurrence-free survival, doubling median liver-specific disease control compared with standard intravenous therapy. Median hepatic recurrence-free survival reached 25 months in the HAI arm versus 12 months with intravenous chemotherapy alone. Overall recurrence-free survival was also significantly prolonged, demonstrating broader disease-control benefits beyond isolated liver recurrence reduction.

Although overall survival did not reach statistical significance, clinically meaningful improvements were observed. Median overall survival approached 74 months in the HAI group compared with 57 months in the intravenous chemotherapy group, with five-year overall survival rates of 62% versus 47%, respectively. These findings suggest a potentially important long-term survival advantage that may become clearer in larger phase III validation studies.

As expected, intensified regional chemotherapy was associated with higher toxicity. Grade 3–4 adverse events occurred more frequently in the HAI arm, although treatment remained feasible overall, with comparable completion rates between groups and no treatment-related deaths. Importantly, toxicity appeared manageable within experienced multidisciplinary hepatobiliary oncology programs.

The study reinforces the concept that recurrence after CRLM surgery is predominantly liver-driven and that intensified liver-directed adjuvant strategies may substantially alter postoperative disease biology in selected high-risk patients. The findings are particularly relevant for patients with extensive bilobar disease or multiple metastases, who remain at greatest risk for early hepatic relapse despite technically curative surgery.

Overall, this important randomized study supports postoperative oxaliplatin-based hepatic arterial infusion as a promising adjuvant strategy for high-risk colorectal liver metastases and provides strong justification for ongoing phase III evaluation of regional chemotherapy intensification after CRLM resection.