Proposal of a new staging system for intrahepatic cholangiocarcinoma: Analysis of surgical patients from a nationwide survey of the Liver Cancer Study Group of Japan

Abstract

Background: In the current American Joint Committee on Cancer/International Union Against Cancer staging system (seventh edition) for intrahepatic cholangiocarcinoma (ICC), tumor size was excluded, and periductal invasion was added as a new tumor classification-defining factor. The objective of the current report was to propose a new staging system for ICC that would be better for stratifying the survival of patients based on data from the nationwide Liver Cancer Study Group of Japan database.

Methods: Of 756 patients who underwent surgical resection for ICC between 2000 and 2005, multivariate analyses of the clinicopathologic factors of 419 patients who had complete data sets were performed to elucidate relevant factors for inclusion in a new tumor classification and staging system.

Results: Overall survival data were best stratified using a cutoff value of 2 cm using a minimal P value approach to discriminate patient survival. The 5-year survival rate of 15 patients who had ICC measuring ≤ 2 cm in greatest dimension without lymph node metastasis or vascular invasion was 100%, and this cohort was defined as T1. Multivariate analysis of prognostic factors for 267 patients with lymph node-negative and metastasis-negative (N0M0) disease indicated that the number of tumors, the presence arterial invasion, and the presence major biliary invasion were independent and significant prognostic factors. The proposed new system, which included tumor number, tumor size, arterial invasion, and major biliary invasion for tumor classification, provided good stratification of overall patient survival according to disease stage. Macroscopic periductal invasion was associated with major biliary invasion and an inferior prognosis.

Conclusions: The proposed new staging system, which includes a tumor cutoff size of 2 cm and major biliary invasion, may be useful for assigning patients to surgery.

Keywords: biliary invasion; intrahepatic cholangiocarcinoma; periductal invasion; staging system; tumor size.

Figure 1

This schematic flow chart displays the population of patients with intrahepatic cholangiocarcinoma (ICC) who underwent hepatectomy between 2000 and 2005 and were registered in the nation‐wide database of the Liver Cancer Study Group of Japan. Combined HCC‐CC indicates combined hepatocellular cholangiocarcinoma; HCC, hepatocellular carcinoma; IG, intraductal growth; MF, mass forming; PI, periductal infiltrating.

Figure 2

This chart illustrates the optimal cutoff value of tumor size for predicting the survival of all 419 patients and of the 267 patients who had lymph node‐negative/metastasis‐negative (N0M0) disease.

Figure 3

These charts compare the staging systems for intrahepatic cholangiocarcinoma based on the stratification of survival curves from the 267 patients who had N0M0 disease according to tumor classification. AJCC 6th indicates the International Union Against Cancer/American Joint Committee on Cancer classification, 6th edition; LCSGJ 5th, Liver Cancer Study Group of Japan, 5th edition; Okabayashi, the staging system published by Okabayashi et al10; AICC 7th, the International Union Against Cancer/American Joint Committee on Cancer classification, 7th edition.

Figure 4

These charts compare the staging systems for intrahepatic cholangiocarcinoma based on the stratification of survival curves from the entire cohort of 419 patients according to disease stage. AJCC 6th indicates the International Union Against Cancer/American Joint Committee on Cancer classification, 6th edition; LCSGJ 5th, Liver Cancer Study Group of Japan, 5th edition; Okabayashi, the staging system published by Okabayashi et al10; AJCC 7th, the International Union Against Cancer/American Joint Committee on Cancer classification, 7th edition.

Figure 5

Overall survival curves are shown for the 337 patients who had incomplete clinicopathologic data stratified according to tumor (T) classification and disease stage defined using the proposed staging system.