Time-to-Interventional Failure as a New Surrogate Measure for Survival Outcomes after Resection of Hepatocellular Carcinoma.

Purpose: This study sought to investigate the clinical impact of repeated interventions for recurrent hepatocellular carcinoma (HCC) and to establish a new surrogate measure for survival: the time-to-interventional failure (TIF).
Methods: Based on a retrospective review of 1158 patients who underwent curative resection for HCC, the abilities of recurrence-free survival (RFS) and TIF, which was defined as the elapsed time from resection to unresectable/unablatable recurrence, to predict overall survival (OS) were compared.
Results: Within a median follow-up period of 84.9 months, 676 (59.0%) recurrence events occurred, 78.1% of which were resectable/ablatable recurrences. Of these, 99.1% of the patients underwent repeated treatments. TIF had a stronger correlation than RFS (r = 0.921 vs. r = 0.631) in prediction of OS. Patients who underwent curative-intent treatment (i.e., resection or ablation) for recurrence showed significantly better survival outcomes compared with those who underwent non-curative treatment (e.g., TACE, chemotherapy) (median OS, 89.1 months vs. 55.0 months; P < 0.0001). This tendency was constant across the AJCC stages and multivariate analysis confirmed that curative-intent treatment is associated with improved survival after initial recurrence (hazard ratio, 0.55; 95% CI, 0.37-0.81; P = 0.003).
Conclusions: OS after HCC resection is more strongly dependent on TIF than on RFS. Aggressive curative-intent interventions for recurrent HCC may prolong survival regardless of the cancer stage.