Treatment Interval as a Prognostic Marker in Patients Undergoing Repeated Curative‐Intent Local Treatment for Recurrent Hepatocellular Carcinoma

PURPOSE: This study aimed to investigate the prognostic impact of the interval between curative-intent local treatments in patients undergoing repeated therapies for recurrent hepatocellular carcinoma after hepatectomy. METHODS: The present retrospective cohort study included 890 patients who underwent hepatectomy for HCC at our hospital between 2001 and 2020. Overall survival (OS) was evaluated from the time of each curative-intent local treatment, according to the number of treatments received and the intervals between consecutive curative-intent treatments for intrahepatic recurrence, up to the fourth session. RESULTS: During follow-up, 625 patients (65.9%) developed intrahepatic recurrence. The median intervals gradually shortened to 24.9, 14.5, 12.4, and 12.8 months from hepatectomy to the first curative treatment, from the first to the second, from the second to the third, and from the third to the fourth treatments, respectively. For the first and second curative treatments, the pretreatment interval was not an independent predictor of OS. At the third curative treatment, an interval < 18.6 months between the second and third curative treatments independently predicted poorer OS (hazard ratio [HR] 2.280 and 95% confidence interval [CI] 1.046-4.967). For the fourth curative treatment, an interval < 14.1 months between the third and fourth treatments was an independent adverse prognostic factor (HR 4.961, 95% CI 1.607-15.319). The prognostic impact of treatment interval was more pronounced in patients who underwent ≥ 3 treatments, with a significant interaction compared with < 3 treatments. CONCLUSIONS: Among patients who remained eligible for repeated curative-intent local treatment, a shortened interval between treatments in late-phase recurrence was an independent predictor of poor prognosis.