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Page 6 of 18 Karademir. Hepatoma Res 2018;4:58 I http://dx.doi.org/10.20517/2394-5079.2018.40

early stage HCC (stages 0 and A) (median OS > 60 mo). For stage B patients, palliation with transarterial
chemoembolization (TACE) is recommended with median OS of 20 months. Sorafenib, multikinase
inhibitor, was added to treatment repertoire in 2008 for patients with advanced disease (stage C) (median
OS = 11 mo). And, for patients at terminal stage with life expectancy of < 3 months, best supportive care is
recommended.

Compared to Okuda and CLIP systems, early stage HCC is defined in more details (number and size of
nodules, the associated comorbidities and the portal vein pressure) in BCLC which makes it more suitable to
select early stage patients who could benefit from curative therapies [15,33] . However, the BCLC has shown to
have lower prognostic ability than CLIP score regarding advance HCC [34,35] .

BCLC has been externally validated in several Western countries where main etiologies are hepatitis C virus
[2]
(HCV) infection and alcohol abuse and are found to have a better ability to predict survival than most
other staging systems [23,36] . Although BCLC has been widely used in Western countries, many Asian experts
find its treatment modalities to be too conservative. In contrast to BCLC, Asian guidelines indicate surgical
resection and TACE for more advanced tumors. Even then, some studies by Asian groups proved BCLC to
[37]
be a superior staging system .
Despite its popularity, several studies have shown that BCLC staging system has some limitations. These
are mainly related to the heterogeneity of BCLC stages B and C patients in respect to tumor burden
[38]
and liver function . For example, patients with multinodular disease without vascular invasion are
assigned to intermediate stage (BCLC B) and only a single therapeutic option, TACE is offered. However,
resectability of multifocal HCC is closely related to location of tumors. A patient with multiple small
tumors confined to the same lobe may still be considered as a good candidate for resection, instead of
transarterial chemoembolization. Additionally, tumors with portal invasion (BCLC C) are recommended
[29]
to be treated only with sorafenib . For these patients, there are studies which suggest extending the
indication for surgery [39-41] or chemoembolization [42,43] . Even for a Child-Pugh C patient with HCC within
the Milan criteria, the possibility of liver transplantation may be considered. On the other end, in BCLC 0
and A patients with early stage HCC, a single liver tumor is resected only in absence of portal hypertension
where it might not affect survival in many resected patients. In current practice, sequential or combined
treatments are highly preferred in the multidisiplinary management of HCC (TACE followed by resection
or LT, TACE + RF or sorafenib). Under these circumstances, BCLC’s one-to-one correspondence treatment
recommendations for each stage may not be suitable for use in actual clinical practice [26,44] . Another critic on
BCLC is regarding the controversial prognostic role of variable ECOG PS which is somewhat subjective and
[45]
may affected by liver function and cancer symptoms .
The BCLC has shown to have lower prognostic ability than CLIP score regarding advance HCC [36,46,47] . A new
[48]
score, advanced liver cancer prognostic system (ALCPS) was proposed by Yau et al. aiming at improving
patients selection but found to be too complex for daily clinical practice as it includes eleven variables with
[9]
different coefficient as in the Chinese University Prognostic Index (CUPI) score .

TNM (AJCC)
The TNM classification was developed by the American Joint Committee on Cancer (AJCC) and
International Union for Cancer Control (UICC) and has been updated regularly since the first edition was
published in 1977. This system is successfully used by oncologists in several fields. However, the classical
staging system based on TNM is not used for HCC. It assesses the extension of the primary tumor, lymph
node involvement and extrahepatic metastasis but does not include any measurements of liver function or
the health status of the patient. Because of this it has often been used in combination with other criteria such
as the Child-Pugh classification or included in other grading systems such as the CLIP score. TNM staging