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The Prognostic Value of Preoperative Serum Markers and Risk Classification in Patients with Hepatocellular Carcinoma

  • Hepatobiliary Tumors
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Abstract

Background

Complex hepatocellular carcinoma (HCC) prognostic biomarkers have been reported in various studies. We aimed to establish biomarkers that could predict prognosis, and formulate a simple classification using non-invasive preoperative blood test data.

Methods

We retrospectively identified 305 patients for a discovery cohort who had undergone HCC-related hepatectomy at four Japanese university hospitals between January 1, 2011 and December 31, 2013. Preoperative blood test parameter optimal cut-off values were determined using receiver operating characteristic curve analysis. Cox uni- and multivariate analyses were used to determine independent prognostic factors. Risk classifications were established using classification and regression tree (CART) analysis. Validation was performed with 267 patients from three other hospitals.

Results

In multivariate analysis, α-fetoprotein (AFP, p < 0.001), protein induced by vitamin K absence or antagonist-II (PIVKA-II, p = 0.006), and C-reactive protein (CRP, p < 0.001) were independent prognostic factors for overall survival (OS). AFP (p = 0.007), total bilirubin (p = 0.001), and CRP (p = 0.003) were independent recurrent risk factors for recurrence-free survival (RFS). CART analysis results formed OS (CRP, AFP, and albumin) and RFS (PIVKA-II, CRP, and total bilirubin) decision trees, based on machine learning using preoperative serum markers, with three risk classifications. Five-year OS (low risk, 80.0%; moderate risk, 56.3%; high risk, 25.2%; p < 0.001) and RFS (low risk, 43.4%; moderate risk, 30.8%; high risk, 16.6%; p < 0.001) risks differed significantly. These classifications also stratified OS and RFS risk in the validation cohort.

Conclusion

Three simple risk classifications using preoperative non-invasive prognostic factors could predict prognosis.

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Acknowledgement

We wish to thank Yuri Ito and Daisuke Nishioka in Osaka Medical and Pharmaceutical University for their valuable advice on the statistical methods. We would like to thank Editage (www.editage.com) for English language editing.

Funding

No funding was received.

Author information

Authors and Affiliations

  1. Department of General and Gastroenterological Surgery, Osaka Medical and Pharmaceutical University, Takatsuki, Osaka, Japan

    Masato Ota MD, Koji Komeda MD, PhD, Fumitoshi Hirokawa MD, PhD & Sang-Woong Lee MD, PhD

  2. Department of Surgery, Shiga University of Medical Science, Shiga, Shiga, Japan

    Hiroya Iida MD, PhD

  3. Second Department of Surgery, Wakayama Medical University, Wakayama, Wakayama, Japan

    Masaki Ueno MD, PhD

  4. Department of Surgery, Kansai Medical University, Hirakata, Osaka, Japan

    Hisashi Kosaka MD, PhD & Masaki Kaibori MD, PhD

  5. Department of Surgery, Nara Medical University, Kashihara, Nara, Japan

    Takeo Nomi MD, PhD & Daisuke Hokutou MD, PhD

  6. Department of Surgery, Uji-Tokusyukai Medical Center, Uji, Kyoto, Japan

    Takeo Nomi MD, PhD

  7. Department of Hepato-Biliary-Pancreatic Surgery, Osaka Metropolitan University of Graduate School of Medicine, Osaka, Osaka, Japan

    Shogo Tanaka MD, PhD & Shoji Kubo MD, PhD

  8. Department of Surgery, Faculty of Medicine, Kindai University, Higashiosaka, Osaka, Japan

    Takuya Nakai MD, PhD & Masataka Matsumoto MD, PhD

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  1. Masato Ota MD
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Correspondence to Masato Ota MD.

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Ota, M., Komeda, K., Iida, H. et al. The Prognostic Value of Preoperative Serum Markers and Risk Classification in Patients with Hepatocellular Carcinoma. Ann Surg Oncol 30, 2807–2815 (2023). https://doi.org/10.1245/s10434-022-13007-9

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  • DOI: https://doi.org/10.1245/s10434-022-13007-9

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