Enhancing Recurrence-Free Survival Prediction in Hepatocellular Carcinoma: A Time-Updated Model Incorporating Tumor Burden and AFP Dynamics.

BACKGROUND

Existing models to predict recurrence-free survival (RFS) after hepatectomy for hepatocellular carcinoma (HCC) rely on static preoperative factors such as alpha-fetoprotein (AFP) and tumor burden score (TBS). These models overlook dynamic postoperative AFP changes, which may reflect evolving recurrence risk. We sought to develop a dynamic, real-time model integrating time-updated AFP values with TBS for improved recurrence prediction.

PATIENTS AND METHODS

Patients undergoing curative-intent hepatectomy for HCC (2000-2023) were identified from an international, multi-institutional database with RFS as the primary outcome. AFP trajectory was monitored from preoperative to 6- and 12-month postoperative values, using time-varying Cox regression with AFP as a time-dependent covariate. The predictive accuracy of this time-updated model was compared with a static preoperative Cox model excluding postoperative AFP.

RESULTS

Among 1911 patients, AFP trajectories differed between recurrent and nonrecurrent cases. While preoperative AFP values were similar, recurrent cases exhibited higher AFP at 6 and 12 months. Multivariable analysis identified TBS (hazard ratio (HR):1.043 [95% confidence interval (CI): 1.002-1.086]; p = 0.039) and postoperative log AFP dynamics (HR:1.216 [CI 1.132-1.305]; p < 0.001) as predictors. Contour plots depicted TBS's influence decreasing over time, while postoperative AFP became more predictive. The time-varying Cox model was created to update RFS predictions continuously on the basis of the latest AFP values. The preoperative Cox model, developed with age, AFP, TBS, and albumin-bilirubin score, had a baseline C-index of 0.61 [0.59-0.63]. At 6 months, the time-varying model's C-index was 0.70 [0.67-0.73] versus 0.59 [0.56-0.61] for the static model; at 12 months, it was 0.70 [0.66-0.73] versus 0.56 [0.53-0.59]. The model was made available online ( https://nm49jf-miho-akabane.shinyapps.io/AFPHCC/ ).

CONCLUSIONS

Incorporating postoperative AFP dynamics into RFS prediction after HCC resection enhanced prediction accuracy over time, as TBS's influence decreased. This adaptive, time-varying model provides refined RFS predictions throughout follow-up.