BACKGROUND: Patients with recurrent hepatocellular carcinoma (HCC) following liver resection can often receive curative treatment, including repeat hepatic resection and local ablative therapy
however, recurrence typically becomes increasingly aggressive during the clinical course characterized by cycles of recurrence and repeated treatment, ultimately resulting in non-curative patterns. METHODS: We defined non-curative recurrences as those involving ≥ 4 liver nodules, macroscopic vascular invasion, and extrahepatic lesions. We first investigated the incidence of non-curative recurrences and survival after non-curative recurrence. We subsequently examined the survival following the initial recurrence separately in patients with curative and non-curative recurrences and compared them. Finally, we investigated whether the time to non-curative recurrences serves as a surrogate for overall survival (OS) in 266 patients undergoing initial curative hepatectomy. RESULTS: The 3-year cumulative incidences of non-curative recurrences were 15.6%, 6.0%, and 11.0% for ≥ 4 liver nodules, macroscopic vascular invasion, and extrahepatic lesions, respectively. Median post-recurrence survivals following these non-curative recurrences were 21, 17, and 8 months, respectively (P =.006). When analyzed exclusively in patient developing initial recurrence, the 3-year post-recurrence survivals were 68.3% and 27.8% for patients with curative and non-curative recurrences, respectively (P =.003). The 3-year survival rate without non-curative recurrences was 71.9%, compared to recurrence-free survival (RFS) and OS of 49.2% and 87.9%, respectively. The concordance index with OS was higher for time to non-curative recurrences (0.88) than RFS (0.67). CONCLUSIONS: These findings suggest that time to non-curative recurrences is a more suitable surrogate for OS than RFS.