Preoperative radioembolization versus chemoembolization and upfront resection for resectable hepatocellular carcinoma beyond the Milan criteria

Abstract Background As the role of transarterial radioembolization (TARE) in resectable hepatocellular carcinoma (HCC) beyond Milan criteria remains undefined, this study compared preoperative TARE and chemoembolization (TACE) with primary resection to establish the optimal management strategy. Materials and methods We retrospectively analyzed HCC patients who did not meet the Milan criteria and underwent primary liver resection, preoperative TACE, or preoperative TARE. Overall survival (OS), time to recurrence (TTR), and recurrence-free survival (RFS) were analyzed using Kaplan–Meier estimates and Cox regression with inverse probability of treatment weighting (IPTW). Results A total of 226 patients were included (primary resection, n = 127; preoperative TACE, n = 52; preoperative TARE, n = 47), with a median follow-up of 37.2 months. After IPTW, baseline characteristics were well balanced. Median OS was not reached in the primary resection and preoperative TARE, but was 60.7 months in the preoperative TACE group. Compared with primary resection, preoperative TACE was associated with worse OS (adjusted HR [aHR]: 2.72; 95% confidence interval [CI] 1.39–5.33; p = 0.004), whereas OS with preoperative TARE was comparable (aHR: 1.14; 95% CI: 0.50–2.55; p = 0.76) after IPTW. Similarly, TTR and RFS were significantly worse in the preoperative TACE (both p = 0.02), whereas no significant differences were observed between the preoperative TARE and primary liver resection groups after IPTW ( p = 0.59 and p = 0.57). Conclusion Preoperative TARE showed no significant difference in survival from primary liver resection in resectable HCC beyond the Milan criteria and may serve as a reasonable alternative strategy when upfront surgery is not feasible. Key Points Question Optimal treatment for resectable hepatocellular carcinoma (HCC) beyond the Milan criteria is controversial. The role of preoperative transarterial radioembolization (TARE) compared with chemoembolization (TACE) or upfront resection remains unclear . Findings Preoperative TARE achieved survival outcomes comparable to primary resection, whereas preoperative TACE was associated with significantly inferior overall and recurrence-free survival . Clinical relevance Preoperative TARE demonstrates survival outcomes comparable to primary resection. It serves as a reasonable therapeutic alternative for resectable hepatocellular carcinoma beyond the Milan criteria, offering effective local control when immediate surgery is not feasible .