Estimation of prognosis estimation is one of the main issues facing physicians when a patient is diagnosed with hepatocellular carcinoma (HCC). Years ago, it was not difficult to estimate prognosis, because the majority of HCC patients were diagnosed at an advanced, symptomatic stage that usually coincided with liver decompensation. At that point, treatment was not feasible, and the short-term prognosis was dismal. Accordingly, HCC patients with impaired performance status or who fit into the Child-Pugh class C category with no chance for being transplanted were classified as end-stage, and these patients were easily recognized in daily clinical practice. This pessimistic scenario has changed completely. More patients receive an early diagnosis of HCC on account of surveillance practices and effective therapy of patients treated at an early stage is associated with a median survival beyond 5 years. Therefore, our aim today, once an HCC has been identified, is to accurately predict the expected outcome and help physicians and their patients to select the best treatment option.
HCC is frequently associated with chronic liver disease and, therefore, any attempt to determine the prognosis should consider not only the tumor burden but also the degree of liver function impairment. Moreover, the assessment of cancer-related symptoms, a well-established procedure in oncology practice, should be incorporated in the prognosis, since symptoms have shown an unquestionable predictive value.[2, 3] Several proposals have been raised to stratify patients according to the expected outcome. Table 1 describes the proposals that have gained more visibility. Most of these proposals resulted from an analysis of the association of any clinical or pathological parameter with survival, ultimately resulting in a division according to an equation derived from the multivariate Cox regression analysis or to a score obtained by the sum of the values allocated to the significant parameters. Unfortunately, in most of these staging systems, there is no assessment of the presence of cancer-related symptoms. Furthermore, any system aimed to be clinically successful should optimally attempt to link prognostic prediction and treatment indication. Regrettably, this is not the case with any of the scoring or category allocation systems, which, to some extent, may include in the same category patients who would be candidates for curative therapy and patients who would merely receive palliation.
|Prognostic System (Year)||N||Tumor Stage||Liver Function||Health Status||Stages/Scores|
|Okuda (1985)||850||Tumor involvement >50%||Bilirubin, albumin, ascites||—||I, II, III|
|CLIP (1998)||435||Tumor morphology, AFP, portal vein invasion||Child-Pugh||—||0-6|
|GRETCH (1999)||761||Portal vein invasion, AFP||Bilirubin, alkaline phosphatase||Karnofsky||A-C|
|BCLC (1999)||Number of nodules, tumor size, portal vein invasion, metastases||Child-Pugh, portal hypertension||Performance status||0, A-D|
|CUPI (2002)||926||TNM, AFP||Bilirubin, ascites, alkaline phosphatase||Symptoms||0-12 (3 risk groups)|
|JIS (2003)||722||TNM by LCSGJ||Child-Pugh||—||0-5|
|SLIDE (2004)||177||TNM by LCSGJ||Liver damage by LCSGJ, PIVKA||—||0-3|
|AJCC TNM (2002)||Number of nodules, tumor size, portal vein invasion, metastases||—||—||I, II, III, IV|
|Tokyo (2005)||403||Number of nodules, tumor size||Albumin, bilirubin||—||0-8|
|Taipei Integrated (2010)||2030||Total tumor volume, AFP||Child-Pugh||—||0-6|
The intent of the Barcelona Clinic Liver Cancer (BCLC) staging system is to surpass the limitations of previous systems. The BCLC classification, which was introduced in 1999 and subsequently refined and updated,[1, 6] is the only system that stratifies patients according to outcome and, simultaneously, links it with treatment indication (Fig. 1). It has been validated in different settings, establishes treatment recommendations for different evolutionary HCCs, and has been supported by prominent scientific societies in the United States and Europe.[7, 8] Finally, a recent meta-analysis analyzing the outcome of 1,927 patients with untreated HCC externally validated the prognostic ability of the BCLC system and confirmed that Eastern Cooperative Oncology Group performance status, degree of liver function impairment, and portal vein thrombosis are robust predictors of death in untreated HCC patients. More interestingly, although a remarkable difference in survival was found between occidental (North American and European) and oriental (Asia-Pacific, with high prevalence of hepatitis B virus–related liver disease) populations, the potential role of hepatitis B virus as a prognostic factor disappeared in the multivariate analysis.