The Oncologic Implications of Tumor Multiplicity in Intrahepatic Cholangiocarcinoma: Its Prognostic Value Might Be Underestimated

In the latest staging system of the American Joint Committee on Cancer for intrahepatic cholangiocarcinoma (IHCCC), solitary tumors with vascular invasion and multiple tumors are grouped together as T2. However, recent studies report that multifocal IHCCC has a worse prognosis than a single lesion. This study aimed to investigate the risk factors for IHCCC and explore the prognostic significance of multiplicity after surgical resection.A total of 257 patients underwent surgery for IHCCC from 2010 to 2019 and the clinicopathological data were retrospectively reviewed. Risk factor analysis was performed to identify variables associated with survival after resection. Survival outcomes were compared between patients with solitary and multiple tumors.In multivariable analysis, the presence of preoperative symptoms, tumor size, lymph node ratio, multiplicity, and tumor differentiation were identified as risk factors for survival. Among 82 patients with T2, overall survival was significantly longer in patients with solitary tumors (sT2) than in those with multiple tumors (mT2) (p=0.017). Survival was compared among patients with stage II-sT2, stage II-mT2, and stage III. The stage II-sT2 group showed prolonged survival when compared with stage II-mT2 or stage III. Survivals of stage II-mT2 and stage III patients were not statistically different.Tumor multiplicity was an independent risk factor for overall survival of IHCCC after surgical resection. Patients with multiple tumors showed poorer survival than patients with a single tumor. The oncologic significance of multiplicity in IHCCC should be reappraised and reflected in the next staging system update.