Factors affecting overall survival and disease-free survival after surgery for hepatocellular carcinoma: a nomogram-based prognostic model-a Western European multicenter study

Abstract

Few studies have assessed the clinical implications of the combination of different prognostic indicators for overall survival (OS) and disease-free survival (DFS) of resected hepatocellular carcinoma (HCC). This study aimed to evaluate the prognostic factors in HCC patients for OS and DFS outcomes and establish a nomogram-based prognostic model to predict the DFS of HCC. A multicenter, retrospective European study was conducted through the collection of data on 413 consecutive treated patients with a first diagnosis of HCC between January 2010 and December 2020. Univariate and multivariate Cox regression analyses were performed to identify all independent risk factors for OS and DFS outcomes. A nomogram prognostic staging model was subsequently established for DFS and its precision was verified internally by the concordance index (C-Index) and externally by calibration curves. For OS, multivariate Cox regression analysis indicated Child-Pugh B7 score (HR 4.29; 95% CI 1.74-10.55; p = 0.002) as an independent prognostic factor, along with Barcelona Clinic Liver Cancer (BCLC) stage ≥ B (HR 1.95; 95% CI 1.07-3.54; p = 0.029), microvascular invasion (MVI) (HR 2.54; 95% CI 1.38-4.67; p = 0.003), R1/R2 resection margin (HR 1.57; 95% CI 0.85-2.90; p = 0.015), and Clavien-Dindo Grade 3 or more (HR 2.73; 95% CI 1.44-5.18; p = 0.002). For DFS, multivariate Cox regression analysis indicated BCLC stage ≥ B (HR 2.15; 95% CI 1.34-3.44; p = 0.002) as an independent prognostic factor, along with multiple nodules (HR 2.04; 95% CI 1.25-3.32; p = 0.004), MVI (HR 1.81; 95% CI 1.19-2.75; p = 0.005), satellite nodules (HR 1.63; 95% CI 1.09-2.45; p = 0.018), and R1/R2 resection margin (HR 3.39; 95% CI 2.19-5.25; < 0.001). The C-Index of the nomogram, tailored based on the previous significant factors, showed good accuracy (0.70). Internal and external calibration curves for the probability of DFS rate showed optimal consistency and fit well between the nomogram-based prediction and actual observations. MVI and R1/R2 resection margins should be considered as significant OS and DFS predictors, while satellite nodules should be included as a significant DFS predictor. The nomogram-based prognostic model for DFS provides a more effective prognosis assessment for resected HCC patients, allowing for individualized treatment plans.

Keywords: HCC; Hepatocellular carcinoma; Liver surgery; Nomogram.