Is the cancer of the liver italian program system an adequate weighting for survival of hepatocellular carcinoma? Evaluation of intrascore prognostic value among 36 subgroups

Background: The Cancer of the Liver Italian Program (CLIP) staging system for hepatocellular carcinoma (HCC) was subdivided into 36 subgroups. We aimed to validate the prognostic value of CLIP scoring. Methods: This study included 3868 HCC cases treated between 1986 and 2002. Survival and prognostic impact of all subgroups were analysed. Results: In primary CLIP, comparisons of each score showed a significant difference (P < 0.001) and exhibited a linear trend (P < 0.001). A CLIP score of 0 was used as control group. Portal vein thrombosis, Child-Pugh B, α-fetoprotein (AFP) ≥ 400 ng/ml and multinodular with tumour extension ≤ 50% of the four subgroups with a CLIP score of 1 exhibited decreasing univariate hazard ratios and 95% confidence intervals, with values of 2.99 (2.05-4.37), 2.39 (2.00-2.86), 1.66 (1.40-1.96) and 1.39 (1.18-1.63) respectively. Homogeneity in the same score was evaluated by comparing subgroup survival curves. For scores 1-5, 83.3% (5/6), 57.1% (16/28), 24.4% (11/45), 3.6% (1/28) and 16.7% (1/6) pairs of survival curves significantly differed, respectively, with decreasing linear trend (P < 0.001). Conclusion: Different prognostic weighting of four predictive factors caused intrascore heterogeneity. Lower CLIP scores were associated with increased differences in intrascore. In conclusion, the CLIP staging scoring system is a reasonable ordinal scale, but the clinician must be aware of the heterogeneity of mortality risk within a given score.