Predictive Value of Dynamic Changes in Serum AFP for Survival in Hepatocellular Carcinoma Patients Treated With TACE Combined With Immunotherapy

Background: Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer-related death worldwide. Serum alpha-fetoprotein (AFP) is widely used as a tumor biomarker for HCC, and its dynamic changes during treatment may reflect tumor response and prognosis. However, the predictive value of AFP dynamics in patients receiving transarterial chemoembolization (TACE) combined with immunotherapy has not been fully clarified. This study aimed to investigate the predictive value of dynamic changes in AFP for survival outcomes in HCC patients treated with TACE combined with immunotherapy. Methods: Clinical data of 267 HCC patients who received TACE combined with immune checkpoint inhibitors at the Second Hospital of Nanjing from January 2021 to January 2024 were retrospectively analyzed. Patients in the AFP–elevated group (n = 199) were divided into an AFP decline group, an AFP stable group, and an AFP progression group according to the dynamic changes in AFP at 8 weeks after the first TACE procedure. Kaplan–Meier method and Cox proportional hazards regression model were used to analyze the relationship between dynamic changes in AFP and overall survival (OS) and progression–free survival (PFS). Restricted cubic spline analysis was used to analyze the nonlinear relationship between AFP change rate and survival outcomes, and the efficacy of predictive models was evaluated using time–dependent receiver operating characteristic (ROC) curves. Results: With a median follow–up of 24.5 months, the median OS and PFS for all patients were 18.5 and 10.2 months, respectively. For patients in the AFP–elevated group, median OS was 20.5 months in the AFP decline group, 14.2 months in the AFP stable group, and 8.5 months in the AFP progression group (p < 0.001). The AFP sustained response group (AFP decline ≥50% from baseline at both 8 and 12 weeks after the first TACE) had significantly longer OS and PFS than the non–sustained response group (26.8 vs 15.5 months for OS, p < 0.001; 14.8 vs 8.2 months for PFS, p < 0.001). Multivariate Cox regression analysis showed that AFP sustained response was independently associated with both OS (hazard ratio [HR] = 0.42, 95% confidence interval [CI] = 0.28–0.63, p < 0.001) and PFS (HR = 0.35, 95% CI = 0.24–0.51, p < 0.001). Barcelona Clinic Liver Cancer (BCLC) stage C, portal vein tumor thrombus, extrahepatic metastasis, and NLR >3.5 were also independent prognostic factors. The combined predictive model predicted 12–month and 24–month OS with AUCs of 0.782 and 0.776, respectively, and Harrell's C–index was 0.748. Subgroup analysis showed that the prognostic value of AFP sustained response was consistent across different clinical subgroups (all p for interaction > 0.05). Competing risk analysis showed that the 24–month cumulative incidence of tumor–related death was 32.8% in the AFP sustained response group and 58.6% in the non–sustained response group (subdistribution HR = 0.38, 95% CI = 0.25–0.58, p < 0.001). Conclusion: Serum AFP sustained response is independently associated with both OS and PFS in HCC patients treated with TACE combined with immunotherapy and may serve as a simple and practical prognostic marker for clinical risk stratification.