Early and very early hepatocellular carcinoma: when and how much do staging and choice of treatment really matter? A multi-center study

Background: A consensus on the most reliable staging system for hepatocellular carcinoma (HCC) is still lacking but the most used is a revised Barcelona Clinic Liver Cancer (BCLC) system, adopted by the American Association for the Study of Liver Diseases (AASLD). We investigated how many patients are diagnosed in very early and early stage, follow the AASLD guidelines for treatment and whether their survival depends on treatment. Methods: Data were collected in 530 very early and early HCC patients recruited by a multicentric Italian collaborative group (ITA.LI.CA). The Kaplan-Meier method was used to estimate overall survival and the log rank to test the statistical significance of difference between groups. Cox's multivariate stepwise regression analysis was used to pinpoint independent prognostic factors and the adjusted relative risks (hazard ratios) were calculated as well. A statistical analysis based on the chi-square test was used to identify significant differences in clinical or pathological features between patients. A P-value < 0.05 was considered statistically significant. Results: Very early HCC were 3%; Cox multivariate analysis did not identify variables independently associated with survival. The patients following AASLD recommendations (20%) did not show longer survival. In early HCC patients (25%), treatment significantly modulated survival (p = 0.0001); the 28% patients treated according to the AASLD criteria survived longer (p = 0,004). The Cox analysis however identified only age, gender, number of lesions and Child class as independent predictors of survival. Conclusion: patients with very early HCC were very few in this analysis. In most instances they were not treated with the treatment suggested as the most appropriate by the AASLD guidelines and the type of treatment had no impact on survival, even though the number of patients was relatively low and part of the patients were diagnosed before the introduction of the guidelines: this analysis, therefore, might not be considered as conclusive and should be validated. The early stage group involved more patients, rarely treated according to the guidelines, both overall and also in those diagnosed after their publication; the survival was in part predicted by the type of treatment, with better results in those treated according to AASLD indications.