Time to Recurrence and BCLC Stage at Recurrence as Critical Variables in Guiding Treatment Decisions for Early-Recurrent Hepatocellular Carcinoma after Liver Resection

Jian-Xi Zhang¹Luo-Bin Guo²Chong-Shi Zeng³Qi-Zhen Huang³Zi-Sen Lai³Meng-Meng Wu³Qingjing Chen³Yong-Ping Lai³Xin-Feng Qiu³Bing Zhang³Jia-Cheng Zhang³Jia-Hui Lv³Li-Ming Huang³Wu-Yi You³Bin Wang³Kong-Ying Lin^3*Alfred Wei Chieh Kow^4*Yongyi Zeng^1*

• ¹The First Affiliated Hospital of Fujian Medical University, Fuzhou, China
• ²Department of Hepatobiliary and Pancreatoscopic Surgery, Mengchao Hepatobiliary Hospital, Fuzhou, China
• ³Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, China
• ⁴National University Hospital, Singapore, Singapore

Background: Patients with Barcelona Clinic Liver Cancer (BCLC) stage 0/A hepatocellular carcinoma (HCC) represent the guideline-recommended population for liver resection; however, treatment strategies for early recurrence after resection remain debated. This study aimed to analyze prognostic factors for survival after recurrence (SAR) in patients with early recurrence following R0 resection of BCLC stage 0/A HCC and to develop evidence-based treatment recommendations integrating time to recurrence (TTR) and BCLC stage at recurrence. Methods: We conducted a retrospective review of 544 patients with early recurrence after R0 resection of BCLC stage 0/A HCC at a tertiary hepatopancreatobiliary academic hospital. Curative treatments included repeat liver resection and ablation, while non-curative treatments comprised transarterial chemoembolization and systemic therapy. Kaplan–Meier methods were applied to estimate SAR, and independent prognostic factors were identified with multivariable Cox regression analysis. Results: The median SAR was 39.4 months, with 1-year, 3-year, and 5-year SAR rates of 81.8%, 52.6%, and 39.0%, respectively. Patients receiving curative treatments demonstrated significantly improved SAR compared with those undergoing non-curative therapies (P < 0.001). Multivariable analysis identified TTR, alpha-fetoprotein level, albumin level, BCLC stage at recurrence, treatment modality, and microvascular invasion in initial tumors as independent prognostic factors for SAR. Subgroup analysis showed that integrating TTR and BCLC stage effectively guided treatment allocation: for BCLC stage A or C disease, treatment should follow current BCLC guidelines, whereas for stage B disease, curative therapy conferred survival benefit when TTR was >6 months but offered no benefit when TTR was ≤6 months. Conclusions: Curative treatments remain an effective option for selected patients with early-recurrent HCC. Treatment allocation based on TTR and BCLC stage at recurrence may optimize outcomes for this population.