Prognostic Nomograms for Patients with Hepatocellular Carcinoma After Curative Hepatectomy, with a Focus on Recurrence Timing and Post-Recurrence Management

Abstract

Wei Xu,* Fei Liu,* Xianbo Shen,* Ruineng Li Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital, The First Hospital Affiliated with Hunan Normal University, Changsha, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei XuDepartment of Hepatobiliary Surgery, Hunan Provincial People’s Hospital, The First Hospital Affiliated with Hunan Normal University, Changsha, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: Prognoses of patients with hepatocellular carcinoma (HCC) after curative hepatectomy remain unsatisfactory because of the high incidence of postoperative recurrence. Published predictive systems focus on pre-resection oncological characteristics, ignoring post-recurrence factors.Purpose: This study aimed to develop prognostic nomograms for 3- and 5-year overall survival (OS) of patients with HCC after curative hepatectomy, focusing on potentially influential post-recurrence factors.Patients and Methods: Clinicopathological and postoperative follow-up data were extracted from 494 patients with HCC who underwent curative hepatectomy between January 2012 and June 2019. Early recurrence (ER) and late recurrence (LR) were defined as recurrence at ≤ 2 and > 2 years, respectively, after curative hepatectomy. Nomograms for the prediction of 3- and 5-year OS were established based on multivariate analysis. The areas under time-dependent receiver operating characteristic curves (AUCs) for the nomograms were calculated independently to verify predictive accuracy. The nomograms were internally validated based on 2000 bootstrap resampling of 75% of the original data.Results: In total, 494 patients with HCC who underwent curative hepatectomy met the eligibility criteria. Cox proportional hazard regression analysis identified factors potentially influencing 3- and 5-year OS. Multivariate analysis indicated that patient age, Hong Kong Liver Cancer stage, γ-glutamyl transferase (γ-GGT) level, METAVIR inflammation activity grade, ER and post-recurrence treatment modality were influencing factors for 3-year OS (AUC, 0.891; 95% CI, 0.8364– 0.9447). γ-GGT > 60 U/L, hepatectomy extent, LR and post-recurrence treatment modality were influencing factors for 5-year OS (AUC, 0.864; 95% CI, 0.8041– 0.9237). Calibration plots showed satisfactory concordance between the predicted and actual observation cohorts.Conclusion: We propose new prognostic nomograms for OS prediction with a focus on the differentiation of recurrence timing and post-recurrence management. These nomograms overcome the shortcomings of previous predictive nomograms and significantly improve predictive accuracy.Keywords: hepatocellular carcinoma, hepatectomy, post-recurrence management, overall survival, nomogram

Keywords

• hepatocellular carcinoma
• hepatectomy
• post-recurrence management
• overall survival
• nomogram