Tumour burden predicts outcomes after curative resection of multifocal intrahepatic cholangiocarcinoma.

Liver resection for multifocal intrahepatic cholangiocarcinoma (ICC) remains controversial due to a poor prognosis, driven by aggressive tumour biology. The aim of this study was to stratify multifocal ICC patients to identify those who are likely to benefit from resection. Patients who underwent upfront curative-intent hepatectomy for ICC were identified from an international multi-institutional database. Among patients with multifocal tumours, overall survival (OS) was analysed using multivariable Cox regression to identify prognostic factors. Tumour burden score (TBS) was used for stratification of multifocal ICC, with the optimal cut-off determined via restricted cubic spline (RCS) analysis. Of 1502 patients, 208 (13.8%) had multifocal ICC. Among them, independent predictors of prognosis included TBS (HR 1.09), ASA grade >II (HR 1.48), cirrhosis (HR 2.05), periductal infiltrating/mass forming plus periductal infiltrating morphological subtype (HR 1.58), and receipt of adjuvant chemotherapy (HR 0.59). RCS analysis identified a TBS of 7.0 as the optimal cut-off. Notably, multifocal ICC patients with a low TBS (<7.0) demonstrated comparable 3-year OS to solitary ICC patients with AJCC stage II/III. In contrast, patients with a high TBS (≥7.0) and multifocal ICC exhibited the worst prognosis (3-year OS: stage I and solitary 67.1%, stage II/III and solitary 43.2%, low TBS and multifocal 43.4%, and high TBS and multifocal 17.8% (P < 0.001)). Whereas patients with high-TBS multifocal ICC had a poor prognosis, individuals with low-TBS multifocal ICC demonstrated survival outcomes comparable to solitary ICC patients. These findings emphasize the importance of stratifying patients by tumour burden to guide surgical decision-making and optimize treatment strategies for multifocal ICC.