Liver cancer: Approaching a personalized care

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 [1Bressac B. Kew M. Wands J. Ozturk M. Selective G to T mutations of p53 gene in hepatocellular carcinoma from southern Africa.Nature. 1991; 350: 429-431https://doi.org/10.1038/350429a0Crossref PubMed Scopus (0) Google Scholar, 2Hsu I.C. Metcalf R.A. Sun T. Welsh J.A. Wang N.J. Harris C.C. Mutational hotspot in the p53 gene in human hepatocellular carcinomas.Nature. 1991; 350: 427-428https://doi.org/10.1038/350427a0Crossref PubMed Scopus (926) Google Scholar] 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]Mazzaferro V. Regalia E. Doci R. Andreola S. Pulvirenti A. Bozzetti F. et al.Liver transplantation for the treatment of small hepatocellular carcinomas in patients with cirrhosis.N Engl J Med. 1996; 334: 693-699Crossref PubMed Scopus (3775) Google Scholar], ii) recognition of ablation as a potentially curative option [4Bruix J. Sherman M. Management of hepatocellular carcinoma: an update.Hepatology. 2011; 53: 1020-1022Crossref PubMed Scopus (2550) Google Scholar, 5EASL-EORTC clinical practice guidelines: management of hepatocellular carcinoma.J Hepatol. 2012; 56 (pii: S0168-8278(11)00873-7): 908-943https://doi.org/10.1016/j.jhep.2011.12.001Abstract Full Text Full Text PDF PubMed Scopus (1359) Google Scholar], iii) proof of benefit of chemoembolization (TACE), [[6]Llovet J.M. Bruix J. Systematic review of randomized trials for unresectable hepatocellular carcinoma: chemoembolization improves survival.Hepatology. 2003; 37: 429-442Crossref PubMed Scopus (1665) Google Scholar] and iv) incorporation of sorafenib as an effective systemic therapy [[7]Llovet J.M. Ricci S. Mazzaferro V. Hilgard P. Gane E. Blanc J.F. et al.Sorafenib in advanced hepatocellular carcinoma.N Engl J Med. 2008; 359 (pii: 359/4/378): 378-390https://doi.org/10.1056/NEJMoa0708857Crossref PubMed Scopus (4330) Google Scholar]. These options are part of the widely endorsed BCLC staging and treatment model (Fig. 1) [8Forner A. Llovet J.M. Bruix J. Hepatocellular carcinoma.Lancet. 2012; 379: 1245-1255Abstract Full Text Full Text PDF PubMed Scopus (1143) Google Scholar, 9Reig M. Darnell A. Forner A. Rimola J. Ayuso C. Bruix J. Systemic therapy for hepatocellular carcinoma: the issue of treatment stage migration and registration of progression using the BCLC-refined RECIST.Semin Liver Dis. 2014; 34: 444-455Crossref PubMed Google Scholar]. This is clinically useful and it will certainly keep evolving to accommodate new scientific evidence.Fig. 1BCLC staging and treatment strategy [as per Semin Liver Dis. 2014 Nov;34(4):444–55]. The figure represents the first approach to the evaluation of the patients with expected prognosis and initial treatment option to be considered. As shown, the upper part of the scheme defines prognosis according to the relevant clinical and tumor related parameters. Bottom part depicts the decision process to select a treatment option for first consideration. As in all recommendations, final treatment indication should take into account a detailed evaluation of additional characteristics (age, comorbidities) of the patients that imply a personalized decision making. ∗Note that Child-Pugh classification is not sensitive to accurately identify those patients with advanced liver failure that would deserve liver transplant consideration. Some patients fitting into Child-Pugh B, and even A, may present a poor prognosis because of clinical events not captured by such system, i.e. spontaneous bacterial peritonitis, recurrent variceal bleeding, refractory ascites with or without hepatorenal syndrome, recurrent encephalopathy, severe malnutrition. ∗∗Patients with end-stage cirrhosis due to heavily impaired liver function (Child-Pugh C or earlier stages with predictors of poor prognosis, high MELD score) should be considered for liver transplantation. In them, HCC may become a contraindication if exceeding the enlistment criteria.View Large Image Figure ViewerDownload Hi-res image Download (PPT)