Real-world Efficacy of CyberKnife Combined with Systemic Therapy for Primary Liver Cancer: Early Dynamic Changes in Alpha-Fetoprotein as a Core Prognostic Factor

Abstract Background: CyberKnife combined with systemic therapy has been increasingly administered to patients with liver cancer, yet its survival benefits in the real world remain unclear. Moreover, the prognostic value of early dynamic changes in alpha-fetoprotein (AFP) following CyberKnife treatment requires further validation. Methods: This retrospective study included 175 patients with liver cancer who received their first CyberKnife treatment between January 2018 and March 2025. Subjects were stratified into the CyberKnife monotherapy group (n=87) and the CyberKnife plus systemic therapy group (n=88) based on treatment modalities. The study compared overall survival, progression-free survival, and objective response rates between the two groups of patients, using multivariate Cox regression to adjust for baseline confounders and identify independent prognostic factors. Results: The median follow-up was 23.6 months. Kaplan-Meier analysis showed that the median overall survival (OS) in the CyberKnife monotherapy group was significantly longer than that in the combination therapy group (57.5 vs. 19.8 months, p=0.005). The median progression-free survival (PFS) was 35.1 vs. 11.3 months (p=0.003). However, after adjustment for baseline confounders via multivariate Cox regression, combination therapy showed no independent association with OS (95% CI: 0.63–2.32, P=0.564) or PFS (95% CI: 0.64–2.46, P=0.518). Post-treatment AFP elevation (versus AFP decline) was an independent adverse prognostic factor for OS (95% CI: 1.23–5.19, P=0.012) and PFS (95% CI: 1.32–5.50, P=0.006). In addition, we conducted several sensitivity analyses, and the results were consistent with the main analysis: there was no significant difference in survival rates between the two groups, and elevated AFP levels remained a significant factor for poor prognosis. Conclusions: Among patients with liver cancer treated with CyberKnife, changes in AFP levels 2–3 months after treatment are a stronger independent prognostic factor than the treatment modality itself; combination with systemic therapy did not provide additional survival benefits.