Submitted:
23 September 2026
Posted:
23 September 2026
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Abstract
Background/Objectives: Hepatocellular carcinoma ³10 cm has a poor prognosis after surgical resection, largely because of extrahepatic recurrence. Neoadjuvant systemic therapy may improve long-term outcomes. We evaluated neoadjuvant systemic therapy followed by hepatectomy versus upfront surgery for large hepatocellular carcinoma. Methods: We retrospectively analyzed the data of 38 consecutive patients with hepatocellular carcinoma ³10 cm who underwent hepatectomy between April 2011 and October 2025. The patients were divided into neoadjuvant systemic therapy (n = 17; atezolizumab plus bevacizumab, n = 8; lenvatinib, n = 9) and upfront surgery (n = 21) groups. Clinicopathological features, perioperative outcomes, recurrence-free survival, and overall survival were compared. Tumor response was assessed using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 and modified RECIST. Results: Baseline characteristics were summarized. Perioperative outcomes, including blood loss, operative time, and morbidity, were similar. The systemic therapy group showed higher 5-year recurrence-free survival (45.2% vs. 16.1%, p = 0.016) and overall survival (75.8% vs. 30.6%, p = 0.037) rates than the upfront surgery group. Overall recurrence was lower in the systemic therapy group (35.3% vs. 90.5%, p < 0.001). Extrahepatic recurrence alone occurred in 42.9% of upfront surgery patients versus none in the systemic therapy group. Descriptive analyses suggested differences in tumor marker and radiological responses between the Atezolizumab plus bevacizumab and lenvatinib subgroups, while overall oncological outcomes were comparable. Liver function remained within acceptable ranges during systemic therapy. Conclusions: Neoadjuvant systemic therapy followed by hepatectomy for hepatocellular carcinoma ≥10 cm was associated with favorable recurrence and survival outcomes compared with historical upfront surgery cases, without an apparent increase in perioperative risk.
Keywords:
bevacizumab
; carcinoma
; hepatocellular
; hepatectomy
; neoadjuvant therapy
; treatment outcome
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