Prognosis of patients with hepatocellular carcinoma. Validation and ranking of established staging-systems in a large western HCC-cohort

Abstract

Background: HCC is diagnosed in approximately half a million people per year, worldwide. Staging is a more complex issue than in most other cancer entities and, mainly due to unique geographic characteristics of the disease, no universally accepted staging system exists to date. Focusing on survival rates we analyzed demographic, etiological, clinical, laboratory and tumor characteristics of HCC-patients in our institution and applied the common staging systems. Furthermore we aimed at identifying the most suitable of the current staging systems for predicting survival.

Methodology/principal findings: Overall, 405 patients with HCC were identified from an electronic medical record database. The following seven staging systems were applied and ranked according to their ability to predict survival by using the Akaike information criterion (AIC) and the concordance-index (c-index): BCLC, CLIP, GETCH, JIS, Okuda, TNM and Child-Pugh. Separately, every single variable of each staging system was tested for prognostic meaning in uni- and multivariate analysis. Alcoholic cirrhosis (44.4%) was the leading etiological factor followed by viral hepatitis C (18.8%). Median survival was 18.1 months (95%-CI: 15.2-22.2). Ascites, bilirubin, alkaline phosphatase, AFP, number of tumor nodes and the BCLC tumor extension remained independent prognostic factors in multivariate analysis. Overall, all of the tested staging systems showed a reasonable discriminatory ability. CLIP (closely followed by JIS) was the top-ranked score in terms of prognostic capability with the best values of the AIC and c-index (AIC 2286, c-index 0.71), surpassing other established staging systems like BCLC (AIC 2343, c-index 0.66). The unidimensional scores TNM (AIC 2342, c-index 0.64) and Child-Pugh (AIC 2369, c-index 0.63) performed in an inferior fashion.

Conclusions/significance: Compared with six other staging systems, the CLIP-score was identified as the most suitable staging system for predicting prognosis in a large German cohort of predominantly non-surgical HCC-patients.

Figure 1. Kaplan-Meier estimated survival curve of 405 HCC-patients.

Median survival was 18.1 months (95%-CI: 15.2–22.2). The 1-, 3-, and 5-year overall survival rates were 63%, 29% and 17%, respectively.

Figure 2. Kaplan-Meier survival analysis stratified according to the Child-Pugh-Score (n = 365).

(No cirrhosis vs. Child A: p = 0.459; Child A vs. Child B: p = 0.009*; Child B vs. Child C: p = 0.016*).

Figure 3. Kaplan-Meier survival analysis stratified according to the TNM-Staging System, 6^th edition (n = 395).

(TNM I vs. TNM II: p<0.0001*; TNM II vs. TNM III: p = 0.012*; TNM III vs. TNM IV: p = 0.03*).

Figure 4. Kaplan-Meier survival analysis stratified according to the Okuda-Score (n = 373).

(Okuda I vs. Okuda II: p<0.0001*; Okuda II vs. Okuda III: p = 0.001*).

Figure 5. Kaplan-Meier survival analysis stratified according to the CLIP-Score (n = 352).

(CLIP 0 vs. CLIP 1: p = 0.262; CLIP 1 vs. CLIP 2: p = 0.001*; CLIP 2 vs. CLIP 3: p = 0.023*; CLIP 3 vs. CLIP≥4: p = 0.005*).

Figure 6. Kaplan-Meier survival analysis stratified according to the BCLC-Score (n = 341).

(BCLC A vs. BCLC B: p = 0.001*; BCLC B vs. BCLC C: p = 0.018*; BCLC C vs. BCLC D: p = 0.005*).

Figure 7. Kaplan-Meier survival analysis stratified according to the JIS-Score (n = 358).

(JIS 0 vs. JIS 1: p = 0.233; JIS 1 vs. JIS 2: p = 0.391; JIS 2 vs. JIS 3: p<0.0001*; JIS 3 vs. JIS 4: p<0.0001*; JIS 4 vs. JIS 5: p<0.0001*).

Figure 8. Kaplan-Meier survival analysis stratified according to the GETCH-Score (n = 304).

(GETCH “low risk group” vs. “medium risk group”: p<0.0001*; GETCH “medium risk group” vs.“high risk group”: p<0.0001*).