Modified staging classification for intrahepatic cholangiocarcinoma based on the sixth and seventh editions of the AJCC/UICC TNM staging systems

Abstract

Intrahepatic cholangiocarcinoma (ICC) was differentiated from hepatocellular carcinoma, as defined in the American Joint Committee on Cancer (AJCC) 6th edition staging manual, using the revised staging system described in the AJCC 7th edition staging manual. This study was conducted to analyze the application of the AJCC 6th and 7th edition staging classifications and to evaluate a modified staging classification to potentially reduce the limitations associated with the different AJCC staging systems.We compared the prognostic value of cancer staging using data from the Surveillance, Epidemiology, and End Results database (N = 2124). The Kaplan-Meier method and Cox regression models were used to analyze survival. The Harrell concordance index (C-index) was used to analyze the discriminative abilities of cancer staging.Patients with stages I and II disease were found to have similar prognoses according to the 6th edition staging system. Using the 7th edition staging system, a low proportion of patients had stage III disease (5.0%), and the hazard ratio (HR) for stage III disease was comparable to that of stage IV disease (stage III and IV, 2.653 and 2.694). We modified the AJCC staging classification by adopting the 7th edition T, N, and M definitions and the 6th edition staging definitions. Consequently, the proportion of patients with stage III disease increased (22.8%). The HR for stage IV disease was higher than that for stage III disease (stage III and IV, 2.425 and 2.956). Meanwhile, the C-index of the modified AJCC staging system was 0.721 (95% CI: 0.696-0.745), which was significantly higher than the AJCC 7th edition staging system (0.694, P < .001), and the AJCC 6th edition staging system (0.712, P = .033). Moreover, in the stratified data, the differences between the stages identified using the modified AJCC staging classification were significant, especially among patients over 60 years in age, white patients and patients who underwent surgery.These findings suggest that the modified AJCC staging classification may be applicable to the staging of ICC and can be adopted in clinical practice.

Figure 1

Consort diagram showing the design of the study. Problems in the American Joint Committee on Cancer (AJCC) 6th and 7th edition staging systems were found, and a modified AJCC staging system was proposed using the SEER series. AJCC = American Joint Committee on Cancer, SEER = Surveillance, Epidemiology, and End Results.

Figure 2

Kaplan–Meier curves of different staging classifications for patients with ICC from the SEER database. The 6th edition AJCC Staging classification (A1 and A2); the 7th edition AJCC Staging classification (B1 and B2); the modified AJCC Staging classification (C1 and C2). Overlap existed for the 6th edition AJCC staging classification of stage I and II disease (P = .569, A1) and of stage IIIb and IIIc disease (P = .512, A2). Overlap existed for the 7th AJCC staging classification of stage III and IVa disease (P = .169, B2), which led to a similar prognosis between stage III and IV disease (P = .087, B1). Survival curves were well separated by stage using the modified AJCC classification (C1 and C2). AJCC = American Joint Committee on Cancer, ICC = intrahepatic cholangiocarcinoma, SEER = Surveillance, Epidemiology, and End Results.