Abstract
BACKGROUND: Although hepatic resection is the most effective curative treatment for hepatocellular carcinoma (HCC) in selected patients, survival outcomes can vary significantly depending on tumor burden and biology. To provide a standardized framework, the oncological resectability classification introduced in 2023 stratifies patients into resectable (R), borderline resectable 1 (BR1), or borderline resectable 2 (BR2). However, the optimal management of patients with BR1 and BR2 in the era of novel systemic therapies remains uncertain. The present study evaluated the surgical validity and treatment strategies for patients with BR1 and BR2, based on this classification. METHODS: A retrospective analysis was conducted on 184 patients who underwent initial hepatic resection for HCC at Nagasaki University Hospital between 2014 and 2024. Clinical variables, perioperative outcomes, the recurrence-free survival (RFS), and the overall survival (OS) were then compared across the 3 groups: R (n = 149), BR1 (n = 21), and BR2 (n = 14). Subgroup analyses were performed to assess the impact of vascular invasion and preoperative systemic therapy. RESULTS: The 5-year RFS rates were 43.9% for R, 39.3% for BR1, and 20.0% for BR2 (p < 0.001). The 5-year OS rates were 75.1% for R, 76.9% for BR1, and 33.8% for BR2 (p < 0.001). Among BR1 patients without vascular invasion, no cancer-related deaths occurred, and recurrence was largely controllable with repeated hepatectomy, radiofrequency ablation, transarterial chemoembolization, or stereotactic radiotherapy in patients even with recurrence. Conversely, BR1 patients with vascular invasion who underwent upfront surgery exhibited poor survival outcomes, whereas those received preoperative systemic therapy demonstrated at least comparable survival outcomes despite a higher tumor burden, with a lower incidence of cancer-related death. BR2 patients had uniformly poor results regardless of vascular invasion. However, two cases who received systemic therapy before surgery achieved a long-term survival, including one with complete pathological necrosis. CONCLUSIONS: BR1 patients, particularly those without vascular invasion, may achieve survival comparable to that of R. In contrast, BR2 patients generally show dismal outcomes with surgery alone, underscoring the necessity of systemic or multimodal approaches. Tailored strategies are essential for optimizing outcomes in patients with borderline resectable HCC.