Narrow-margin hepatectomy combined with external beam radiotherapy in patients with hepatocellular carcinoma: a systematic review and meta-analysis

There is still controversy regarding which adjuvant treatment should be used after hepatectomy to reduce recurrence and prolong survival. This study aims to compare the short-term and long-term outcomes between narrow margin hepatectomy combined with external beam radiotherapy (EBRT) and narrow margin hepatectomy alone in hepatocellular carcinoma (HCC) patients. We conducted comprehensive searches in PubMed, Embase, the Cochrane Library, and Web of Science from database inception to March 2025. Eligible studies were those comparing narrow-margin hepatectomy with EBRT versus narrow-margin hepatectomy alone in HCC patients and reporting recurrence or survival. Meta-analysis was subsequently performed to pool data and assess therapeutic efficacy. The analysis included eight studies with 1,057 patients, of whom 461 underwent narrow-margin hepatectomy with EBRT and 596 underwent narrow-margin hepatectomy alone. For disease-free survival (DFS), The pooled HRs (hazard ratios) was 0.6(95% CI: 0.49–0.74). The pooled ORs (odds ratios) for 1-, 3-, and 5-year outcomes were 2.47 (95% confidence interval [CI]: 1.75–3.49), 2.00 (95% CI: 1.52–2.63), and 2.20 (95% CI: 1.63–2.96), respectively. For overall survival (OS), the pooled HRs was 0.68(95% CI: 0.52–0.88). The pooled ORs for 1-, 3-, and 5-year outcomes were 3.86 (95% CI: 1.88–7.96), 1.97 (95% CI: 1.42–2.74), and 1.73 (95% CI: 1.29–2.33), respectively. In terms of recurrence, the OR for intrahepatic recurrence was 0.57 (95% CI: 0.42–0.78) in the EBRT combination group, while the OR for extrahepatic recurrence was 0.60 (95% CI: 0.37–0.96). Subgroup analyses showed that the combined treatment provided a significant advantage in all but two subgroup, which demonstrated a non-significant trend. Sensitivity analyses confirmed that these pooled results were robust. A total of 17 cases (4.42%) of grade 3 adverse events (AEs) were reported, with no grade ≥ 4 AEs observed. This study indicates that narrow-margin hepatectomy combined with adjuvant EBRT can reduce tumor recurrence and prolong survival in HCC patients. However, additional high-quality RCTs evaluating this combined strategy are required for validation.