A National Assessment of T2 Staging for Intrahepatic Cholangiocarcinoma and the Poor Prognosis Associated with Multifocality

T2 intrahepatic cholangiocarcinoma (ICC) is defined as a solitary tumors with vascular invasion or multifocal tumors including satellite lesions, multiple lesions, and intrahepatic metastases. This study aimed to evaluate the prognosis associated with multifocal tumors.

The National Cancer Database was queried from 2004 to 2017 for patients with non-metastatic ICC. The patients were grouped based on T2 staging, multifocality, and lymph node involvement.

The study enrolled and classified 4887 patients into clinical (c) stage groups as follows: 15.2% with solitary T2N0 (sT2N0) tumors, 21.3% with multifocal T2N0 (mT2N0) tumors, and 63.5% with node-positive (TxN1) disease. Patients with (c)sT2N0 tumors had higher rates of surgical resection than those with (c)mT2N0 or (c)TxN1 disease (33.5% vs 19.7% vs 15.0%; p < 0.01). Median overall survival (OS) was better for the patients with (c)sT2N0 tumors than for those with multifocal and node-positive disease (15.4 vs 10.4 vs 10.4 months; p < 0.01). On multivariate analysis, (c)sT2N0 tumors were associated with better OS than (c)mT2N0 tumors [hazard ratio (HR), 1.31; 95% confidence interval (CI), 1.17–1.46; p < 0.01] or (c)TxN1 disease (HR,1.41; 95% CI 1.28–1.56; p < 0.01). In a subset analysis based on pathologic (p) staging of patients who underwent surgical resection with regional lymphadenectomy, multivariate analysis demonstrated that (p)sT2N0 tumors were associated with better OS than (p)mT2N0 tumors (HR,1.40; 95% CI 1.03–1.92; p = 0.03) or (p)TxN1 disease (HR, 2.05; 95% CI 1.62–2.58; p < 0.01).

Multifocal T2N0 ICC is associated with poor OS and has a disparate prognosis compared with solitary T2N0 disease, even among patients who undergo resection. Future staging criteria should account for the poor outcomes associated with multifocal ICC.