Abstract Objectives This study compared the efficacies of proton beam therapy (PBT) alone and PBT after transarterial chemoembolisation (TACE) in patients with hepatocellular carcinoma (HCC). Methods We retrospectively studied 917 patients with HCC treated with PBT alone (PBT group, n = 354) or PBT following TACE (TACE-PBT group, n = 563) between 2016 and 2024. Results Before propensity score matching (PSM), there were no significant differences in local control (LC) or overall survival (OS). After PSM, there was no difference in OS between the two groups (p = 0.124), while LC showed a trend toward favoring TACE-PBT group (2-year LC: 97.4% vs. 94.8%, p = 0.068). In the subgroup of patients with mALBI grade 1 and absence of portal vein tumor thrombus, both LC and OS were significantly improved (p = 0.017 and p = 0.002, respectively). Moreover, there were no significant differences in mALBI grade distribution at 1, 3, and 6 months post-treatment (p = 0.231, p = 0.158, and p = 0.683, respectively). Conclusions While adding TACE before PBT marginally improved LC, it did not confer any benefit in the OS. Given the excellent LC achieved with PBT alone, the modest absolute benefit of adding TACE should be carefully weighed against individual patient factors. Advances in knowledge This first large-scale study comparing PBT alone and TACE-PBT in HCC patients, demonstrating that PBT alone achieves excellent LC, with limited additional benefit from TACE except in selected subgroups. These findings help refine patient selection for combined therapy to maximize clinical benefit.
Cheng et al. (2026) studied this question.