The time to non-curative recurrence following liver resection as an appropriate surrogate measure for overall survival in patients with hepatocellular carcinoma.

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.