Prognostic models for outcome prediction in patients with advanced hepatocellular carcinoma treated by systemic therapy: a systematic review and critical appraisal

Objective To describe and analyze the predictive models of the prognosis of patients with hepatocellular carcinoma (HCC) undergoing systemic treatment. Design Systematic review. Data sources PubMed and Embase until December 2020 and manually searched references from eligible articles. Eligibility criteria for study selection The development, validation, or updating of prognostic models of patients with HCC after systemic treatment. Results The systematic search yielded 42 eligible articles: 28 articles described the development of 28 prognostic models of patients with HCC treated with systemic therapy, and 14 articles described the external validation of 32 existing prognostic models of patients with HCC undergoing systemic treatment. Among the 28 prognostic models, six were developed based on genes, of which five were expressed in full equations; the other 22 prognostic models were developed based on common clinical factors. Of the 28 prognostic models, 11 were validated both internally and externally, nine were validated only internally, two were validated only externally, and the remaining six models did not undergo any type of validation. Among the 28 prognostic models, the most common systemic treatment was sorafenib ( n = 19); the most prevalent endpoint was overall survival ( n = 28); and the most commonly used predictors were alpha-fetoprotein ( n = 15), bilirubin ( n = 8), albumin ( n = 8), Child–Pugh score ( n = 8), extrahepatic metastasis ( n = 7), and tumor size ( n = 7). Further, among 32 externally validated prognostic models, 12 were externally validated > 3 times. Conclusions This study describes and analyzes the prognostic models developed and validated for patients with HCC who have undergone systemic treatment. The results show that there are some methodological flaws in the model development process, and that external validation is rarely performed. Future research should focus on validating and updating existing models, and evaluating the effects of these models in clinical practice. Systematic review registration PROSPERO CRD42020200187 .