Prognostic Implications of Recurrence Patterns and Time to Recurrence in Post-Hepatectomy Hepatocellular Carcinoma...

Post-recurrence survival (PRS) after hepatectomy for hepatocellular carcinoma (HCC) varies widely, yet the prognostic significance of the recurrence pattern and time to recurrence (TTR) for PRS remains incompletely defined. This single-center retrospective study included 126 patients with first HCC recurrence after curative hepatectomy (2018-2024) and aimed to explore the prognostic role of recurrence pattern, classified as low-risk (oligo-recurrence: ≤3 intrahepatic nodules, each ≤3 cm) or high-risk (multiple/large intrahepatic, tumor in vein, or extrahepatic), for PRS. In the overall cohort, the recurrence pattern independently predicted PRS (hazard ratio 2.13, p = 0.015); the preoperative Barcelona Clinic Liver Cancer (BCLC) stage, gamma-glutamyl transferase, and total bilirubin were also independent predictors. A sensitivity analysis, including post-recurrence treatment, attenuated the hazard ratio for high-risk pattern to 1.82 (95% CI 0.93-3.55, p = 0.079), consistent with partial mediation. Kaplan-Meier analyses suggested an association between shorter TTR and worse overall survival (OS), but this finding is descriptive because OS measured from surgery is mathematically coupled with TTR. In an exploratory subgroup analysis of patients with early-stage primary HCC (BCLC 0/A, n = 98), the recurrence pattern showed a borderline association with PRS (p = 0.053). Late detection was associated with high-risk recurrence but did not independently affect survival. These findings highlight the prognostic value of the recurrence pattern for PRS and support the consideration of TTR as a descriptive prognostic indicator, which together may inform risk-adapted follow-up and treatment strategies.