Impact of Prior Treatment History on Recurrence After Complete Response to Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma

AIM: Integration of locoregional treatments (LRTs) with atezolizumab plus bevacizumab (atezo/bev) has improved treatment outcomes, enabling an increasing number of patients with unresectable hepatocellular carcinoma (HCC) to achieve a complete response (CR). A comprehensive analysis of recurrence following CR may provide insights into prognosis. This study aimed to identify the factors associated with post-CR recurrence in unresectable HCC. METHODS: This retrospective study included 15 patients with unresectable HCC who achieved CR with atezo/bev therapy. The incidence and characteristics of post-CR recurrence were analyzed. RESULTS: Ten patients achieved CR by combining LRT with atezo/bev, whereas five achieved CR with atezo/bev alone. The post-CR recurrence rate was 53.3% (recurrence group, n = 8; non-recurrence group, n = 7). No significant differences were observed between the recurrence and non-recurrence groups in HCC treatment history prior to atezo/bev initiation, predictive factors for treatment response, including the neutrophil-to-lymphocyte ratio, hepatic functional reserve, and tumor burden at the initiation of atezo/bev, treatment progress, or frequency of atezo/bev maintenance therapy post-CR. In multivariate analysis, a history of ≥ 2 HCC treatments prior to atezo/bev initiation was independently associated with post-CR recurrence (hazard ratio, 6.744; 95% confidence interval, 1.189-38.25; p = 0.031); conversely, predictive factors for atezo/bev response, treatment progress, and maintenance therapy did not contribute to post-CR recurrence. CONCLUSIONS: Given the high post-CR recurrence rate with atezo/bev in unresectable HCC, vigilant surveillance remains essential even after achieving CR, particularly in patients with ≥ 2 prior HCC treatments before atezo/bev initiation.