Background
Prognostic assessment in patients with hepatocellular carcinoma (HCC) remains controversial. Using the Italian Liver Cancer (ITA.LI.CA) database as a training set, we sought to
develop and validate a new prognostic system for patients with HCC.
Methods and Findings
Prospective collected databases from Italy (training cohort, n = 3,628; internal validation
cohort, n = 1,555) and Taiwan (external validation cohort, n = 2,651) were used to develop the ITA.LI.CA prognostic system. We first defined ITA.LI.CA stages (0, A, B1, B2, B3, C)
using only tumor characteristics (largest tumor diameter, number of nodules, intra- and
extrahepatic macroscopic vascular invasion, extrahepatic metastases). A parametric multivariable survival model was then used to calculate the relative prognostic value of ITA.LI.
CA tumor stage, Eastern Cooperative Oncology Group (ECOG) performance status, Child\u2013
Pugh score (CPS), and alpha-fetoprotein (AFP) in predicting individual survival. Based on
the model results, an ITA.LI.CA integrated prognostic score (from 0 to 13 points) was constructed, and its prognostic power compared with that of other integrated systems (BCLC,
HKLC, MESIAH, CLIP, JIS). Median follow-up was 58 mo for Italian patients (interquartile
range, 26\u2013106 mo) and 39 mo for Taiwanese patients (interquartile range, 12\u201361 mo).
The ITA.LI.CA integrated prognostic score showed optimal discrimination and calibration
abilities in Italian patients. Observed median survival in the training and internal validation
sets was 57 and 61 mo, respectively, in quartile 1 (ITA.LI.CA score 1), 43 and 38 mo in
quartile 2 (ITA.LI.CA score 2\u20133), 23 and 23 mo in quartile 3 (ITA.LI.CA score 4\u20135), and 9
and 8 mo in quartile 4 (ITA.LI.CA score > 5). Observed and predicted median survival in the
training and internal validation sets largely coincided. Although observed and predicted survival estimations were significantly lower (log-rank test, p < 0.001) in Italian than in Taiwanese patients, the ITA.LI.CA score maintained very high discrimination and calibration
features also in the external validation cohort.
The concordance index (C index) of the ITA.LI.CA score in the internal and external validation cohorts was 0.71 and 0.78, respectively. The ITA.LI.CA score\u2019s prognostic ability was
significantly better (p < 0.001) than that of BCLC stage (respective C indexes of 0.64 and
0.73), CLIP score (0.68 and 0.75), JIS stage (0.67 and 0.70), MESIAH score (0.69 and 0.77),
and HKLC stage (0.68 and 0.75). The main limitations of this study are its retrospective
nature and the intrinsically significant differences between the Taiwanese and Italian groups.
Conclusions
The ITA.LI.CA prognostic system includes both a tumor staging\u2014stratifying patients with
HCC into six main stages (0, A, B1, B2, B3, and C)\u2014and a prognostic score\u2014integrating
ITA.LI.CA tumor staging, CPS, ECOG performance status, and AFP. The ITA.LI.CA prognostic system shows a strong ability to predict individual survival in European and Asian populations
