Comparative efficacy and safety of postoperative adjuvant therapies after curative resection for hepatocellular carcinoma: a network meta-analysis

Purpose Hepatocellular carcinoma (HCC) has a high risk of recurrence even after curative-intent hepatic resection. Although several postoperative adjuvant therapies have been investigated, the optimal strategy remains uncertain because direct head-to-head comparisons are limited. This study aimed to compare and rank the efficacy and safety of adjuvant therapies for HCC using a network meta-analysis (NMA). Methods A systematic search of MEDLINE via PubMed, Embase, CENTRAL, Web of Science, Scopus, regional databases, clinical trial registries, and conference proceedings was conducted to identify randomized controlled trials evaluating postoperative adjuvant therapies after curative-intent hepatic resection for HCC. The primary outcome was recurrence-free survival (RFS); secondary outcomes included overall survival (OS) and safety. A frequentist NMA was performed to estimate pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Treatments were ranked using P -scores. Results Twenty-eight randomized controlled trials involving 4,830 participants were included. Most patients had hepatitis B virus-related HCC and preserved liver function (Child–Pugh A). For OS, adjuvant 125 I-brachytherapy (HR = 0.36, 95%CI 0.17–0.78), IMRT (HR = 0.44, 95%CI 0.23–0.86), and 131 I-metuximab (HR = 0.46, 95%CI 0.28–0.77) were associated with the greatest reductions in mortality compared with observation. For RFS, autologous formalin-fixed tumor vaccine (AFTV) ranked highest ( P -score = 0.92), followed by adjuvant Cidan capsule plus TACE (0.90), 125 I-brachytherapy (0.84), and IMRT (0.80). Most therapies showed manageable toxicity. Immune checkpoint inhibitors demonstrated a favorable benefit-risk profile, while locoregional therapies were associated with expected procedure-related adverse events. Conclusion Internal radiation and brachytherapy approaches ( 125 I-brachytherapy, IMRT, and 131 I-metuximab) were associated with the greatest OS benefit, whereas AFTV and adjuvant Cidan capsule plus TACE showed the strongest RFS in the network. However, this finding is based on limited evidence (single small trial) and should be considered hypothesis-generating rather than definitive. These findings support risk-adapted integration of radiotherapy and immunotherapy after resection, although further large-scale head-to-head trials are needed.