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

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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.

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Data are available on request to the corresponding author.

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Funding

All authors declare no sources of funding for this study.

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Author notes

  1. Yoshio Masuda and Mark Yeo Hao Xuan have shared first author.

Authors and Affiliations

  1. Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Yoshio Masuda & Mark Hao Xuan Yeo

  2. Ministry of Health Holdings Singapore, Singapore, Singapore

    Yoshio Masuda & Mark Hao Xuan Yeo

  3. Hepato Pancreato Biliary Division, Department of Hepato-Pancreato-Biliary Surgery, Hospital del Mar, Universitat Pompeu Fabra, Passeig Marítim de la Barceloneta, 25, 29, 08003, Barcelona, Spain

    Fernando Burdio, Patricia Sanchez-Velazquez, Marc Perez-Xaus, Amalia Pelegrina & Benedetto Ielpo

  4. Department of Hepato-Pancreato-Biliary and Transplant Surgery, Singapore General Hospital, Singapore, Singapore

    Ye Xin Koh, Brian K.P. Goh, Ek Khoon Tan & Jin Yao Teo

  5. Duke-National University of Singapore Medical School, Singapore, Singapore

    Ye Xin Koh, Brian K.P. Goh, Ek Khoon Tan & Jin Yao Teo

  6. Hepatobiliary Unit, Department of General and Digestive Surgery, Hospital Universitario La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP), Universidad Autónoma de Madrid (UAM), Madrid, Spain

    Marcello Di Martino

  7. Department of Surgery, School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy

    Fabrizio Romano

  8. Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Italy

    Simone Famularo

  9. HPB Surgical Unit, San Paolo Hospital, Savona, Italy

    Cecilia Ferrari & Guido Griseri

  10. Department of General and Digestive Surgery, Hôpital Robert Debré, Centre Hospitalier Universitaire de Reims, Université de Reims Champagne-Ardenne, Reims, France

    Tullio Piardi & Daniele Sommacale

  11. School of Medicine and Surgery, Milano-Bicocca University and HPB Unit, IRCCS San Gerardo Hospital, Monza, Italy

    Luca Gianotti

  12. Department of Clinical and Experimental Sciences, Surgical Clinic, University of Brescia, Brescia, Italy

    Sarah Molfino & Gianluca Baiocchi

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  1. Yoshio Masuda
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Contributions

Conceptualization, BI; Methodology, YM, MYHX, FB, MP, BI; Validation, PSV, AP, KYX, MDM, BI; Formal Analysis, YM, MYHX, FB; Investigation, YM, MYHX, BI; Resources, YM, MYX, BI; Data Curation, YM, MYHX, FB, PSV, MP, AP, KYX, MDM, FR, SF, CF, GG, TP, DS, LG, SM, GB, BI; Writing—Original Draft Preparation, YM, MY, FB, PSV, MP, AP, BI; Writing—Review and Editing, YM, MYHX, FB, PSV, MP, AP, KYX, MDM, GKPB, TEK, TJY, FR, SF, CF, GG, TP, DS, LG, SM, GB, BI; Visualization, BI; Supervision, BI; Project Administration, YM, MYHX, BI.

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Correspondence to Benedetto Ielpo.

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Masuda, Y., Yeo, M., Burdio, F. et al. Factors affecting overall survival and disease-free survival after surgery for hepatocellular carcinoma: a nomogram-based prognostic model—a Western European multicenter study. Updates Surg 76, 57–69 (2024). https://doi.org/10.1007/s13304-023-01656-8

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