Liver cancer: Approaching a personalized care

Abstract

The knowledge and understanding of all aspects of liver cancer [this including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA)] have experienced a major improvement in the last decades. New laboratory technologies have identified several molecular abnormalities that, at the very end, should provide an accurate stratification and optimal treatment of patients diagnosed with liver cancer. The seminal discovery of the TP53 hotspot mutation [1,2] was an initial landmark step for the future classification and treatment decision using conventional clinical criteria blended with molecular data. At the same time, the development of ultrasound, computed tomography (CT) and magnetic resonance (MR) has been instrumental for earlier diagnosis, accurate staging and treatment advances. Several treatment options with proven survival benefit if properly applied are now available. Major highlights include: i) acceptance of liver transplantation for HCC if within the Milan criteria [3], ii) recognition of ablation as a potentially curative option [4,5], iii) proof of benefit of chemoembolization (TACE), [6] and iv) incorporation of sorafenib as an effective systemic therapy [7]. These options are part of the widely endorsed BCLC staging and treatment model (Fig. 1) [8,9]. This is clinically useful and it will certainly keep evolving to accommodate new scientific evidence. Fig. 1 BCLC staging and treatment strategy This review summarises the data which are the basis for the current recommendations for clinical practice, while simultaneously exposes the areas where more research is needed to fulfil the still unmet needs (Table 1). Table 1 Major unmet needs in the field of HCC. Keywords: Liver cancer, HCC, iCCA, Profiling, Personalised treatment Epidemiology Liver cancer (including HCC and iCCA) is the 2nd cause of cancer related death [10] and one of the cancers with a still increasing incidence rate [11]. Since risk factors are well known, prevention is an achievable aim. Control of hepatitis B (HBV) and C (HCV) infection, as well as reduction in alcohol consumption would have a huge impact if applied on a large scale. While health plans are implemented to achieve this goal, the epidemic of overweight and metabolic syndrome has emerged as a relevant risk factor [12]. Prospective follow-up data about incidence and specific high-risk individuals in this subset as compared to HBV, HCV or alcohol are still scarce. However, the future reduction in viral related cases because of HBV and HCV control is counterbalanced by the increase in such an etiologic group. Cancer related death will decrease due to a reduction in exposure to risk factors and because of a higher rate of early diagnosis leading to effective treatment with long term disease free survival. This is the basis to recommend screening for HCC in the population at risk [4,5]. Some restrictions should be in place to make screening cost-effective [13]. Risk should be high enough and modelling studies have placed such cut-offs at an annual rate of 1.5% [14]. Such a figure is exceeded in liver cirrhosis of most etiologies [15,16]. In addition, patients entering screening should be suitable for treatment if they would be diagnosed with HCC. If comorbidities or end-stage liver disease not leading to transplant exist, screening and diagnosis of HCC and its potential treatment will be of no benefit. Finally, diagnosis, accurate and effective options should be available. Unfortunately, an unknown proportion of patients with cirrhosis may not be yet diagnosed, and even so, implementation of screening is usually suboptimal. In the future, the evaluation of the specific risk in an individual patient and prognostic prediction will be refined by molecular profiling of the oncogenic cirrhotic liver and the tumor.