Alpha-fetoprotein as a prognostic factor in alpha-fetoprotein-negative hepatocellular carcinoma - integration into...

This study aimed to validate the prognostic value of alpha- fetoprotein (AFP) in AFP-negative hepatocellular carcinoma (HCC) and develop an AFP-integrated nomogram for post-resection recurrence-free survival (RFS) and overall survival (OS).

This retrospective study analyzed 453 HCC patients with preoperative AFP ≤ 20 ng/ml who underwent curative resection, divided into training (n = 317) and validation (n = 136) cohorts. The optimal AFP cutoff was determined using maximized χ² values. Nomograms were developed with repeated least absolute shrinkage and selection operator variable selection and stepwise Cox regression. Model performance was assessed using concordance (C-) indices, time-dependent area under the receiver operating characteristic curves (AUCs), calibration plots, and Kaplan-Meier (KM) curves.

An alpha-fetoprotein cutoff of 7 ng/ml stratified patients for both RFS and OS (p < 0.001). The recurrence-free survival nomogram included AFP, age, sex, multiple tumors, and cirrhosis, while the OS nomogram incorporated AFP, albumin-bilirubin score, the up-to-7 criterion, des-γ-carboxy prothrombin, vascular invasion, and histological grade. In the training cohort, the nomograms demonstrated C-indices of 0.64 (95% CI: 0.60-0.68) for RFS and 0.72 (0.67-0.76) for OS. Validation cohort C-indices were 0.64 (0.62-0.65) for RFS and 0.67 (0.65-0.68) for OS. Time-dependent AUCs and calibration plots confirmed the predictive accuracy of the nomograms, and KM curves showed clear separation between high- and low-risk groups, further highlighting their clinical utility.

Alpha-fetoprotein retains prognostic value even within the clinically normal range for HCC. The AFP-integrated post-resection nomograms demonstrated acceptable predictive performance for AFP-negative patients, potentially enhancing personalized management strategies.