Prognosis of unresectable hepatocellular carcinoma: comparison of seven staging systems (TNM, Okuda, BCLC, CLIP, CUPI, JIS, CIS) in a Chinese cohort

Abstract

Background: Many liver staging systems that include the tumor stage and the extent of liver function have been developed. However, prognosis assessment for hepatocellular carcinoma (HCC) remains controversial. In this study, the performances of 7 staging systems were compared in a cohort of patients with HCC who underwent non-surgical treatment.

Methods: A total of 196 consecutive patients with HCC who underwent non-surgical treatment seen between January 1, 2004, and December 31, 2007, were included. Performances of TNM sixth edition, Okuda, Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), Chinese University Prognostic Index (CUPI), Japan Integrated Staging (JIS), and China integrated score (CIS) have been compared and ranked using concordance index (c-index). Predictors of survival were identified using univariate and multivariate Cox model analyses.

Results: The median survival time for the cohort was 7.6 months (95% CI 5.6-9.7). The independent predictors of survival were performance status (P<.001), serum sodium (P<.001), alkaline phosphatase (P<.001), tumor diameter greater than 5 cm (P = .001), portal vein invasion (P<.001), lymph node metastasis (P = .025), and distant metastasis (P = .004). CUPI staging system had the best independent predictive power for survival when compared with the other six prognostic systems. Performance status and serum sodium improved the discriminatory ability of CUPI.

Conclusion: In our selected patient population whose main etiology is hepatitis B, CUPI was the most suitable staging system in predicting survival in patients with unresectable HCC. BCLC was the second top-ranking staging system. CLIP, JIS, CIS, and TNM sixth edition were not helpful in predicting survival outcome, and their use is not supported by our data.

Figure 1. Survival curves for patients with unresectable hepatocellular carcinoma who were stratified according to the TNM sixth edition staging system.

Stage I versus II, P = .704; stage II versus III, P = .009; stage III Versus IV, P = .000. The difference between stage I and II was not statistically significant.

Figure 2. Survival curves for patients with unresectable hepatocellular carcinoma who stratified according to the Okuda staging system.

Stage 1 versus 2, P = .015; stage 2 versus 3, P = .010. Statistical difference was noted between any stages.

Figure 3. Survival curves for patients with unresectable hepatocellular carcinoma who were stratified according to the Barcelona Clinic Liver Cancer staging system.

Stage A versus B, P = .045; stage B versus C, P = .022; stage C versus D, P = .000. All difference between groups was statistically significant.

Figure 4. Survival curves for patients with unresectable hepatocellular carcinoma who stratified according to the Cancer of the Liver Italian Program staging system.

Score 0 versus 1, P = .050; score 1 versus 2, P = .056; score 2 versus 3, P = .412; score 3 versus 4, P = .518; score 4 versus 5, P = .033; score 5 versus 6, P = .464. No statistical differences were noted between any scores.

Figure 5. Survival curves for patients with unresectable hepatocellular carcinoma who stratified according to the Chinese University Prognostic Index.

Low risk versus intermediate risk, P = .013; intermediate risk versus high risk, P = .000; low risk versus high risk, P = .000. All differences between scores were statistically significant.

Figure 6. Survival curves for patients with unresectable hepatocellular carcinoma who were stratified according to the Japan Integrated Staging System.

Score 0 versus 1, P = .322; score 1 versus 2, P = .655; score 2 versus 3, P = .046; score 3 versus 4, P = .000; score 4 versus 5, P = .980. The difference was significant only between scores of 2 and 3 and between scores of 3 and 4.

Figure 7. Survival curves for patients with unresectable hepatocellular carcinoma who stratified according to the China Integrated Score.

Score 0 versus 1, P = .366; score 1 versus 2, P = .004; score 2 versus 3, P = .056; score 3 versus 4, P = .093; score 4 versus 5, P = .853. The difference was significant only between scores of 1 and 2.