Prognostic implications of tumour number in intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (ICC) with multiple liver tumours is staged as T2 disease in the 8^th edition of the AJCC staging system. However, tumour multiplicity is frequently associated with poor prognosis in ICC. We aimed to elucidate the prognosis of ICC with multiple tumours and the impact of the number of liver tumours on survival.

Patients who were diagnosed with ICC with solitary liver tumours or multiple liver tumours between May 2008 and December 2019 at three tertiary referral centres in Hong Kong, Seoul and Shanghai were enrolled. Kaplan-Meier analyses and multivariable Cox proportional hazards models were used to analyse the association between tumour multiplicity and overall survival (OS).

A total of 849 patients were included in the analysis. Among the 563 patients without distant metastasis, 434 (77.1%) and 129 (22.9%) had solitary and multiple liver tumours at baseline, respectively. The median follow-up period was 91.9 months (IQR 69.6-131.5). Median OS for patients with a solitary liver tumour, multiple liver tumours, and distant metastasis was 39.5 months (95% CI 34.4-49.2), 14.8 months (11.4-20.3), and 7.1 months (95% CI 6.1-8.3), respectively (log-rank p <0.001). Among N0M0 patients with multiple liver tumours, those with 2-3 tumours and those with ≥4 tumours had a median OS of 36.9 months (16.0-NA) and 15.5 months (11.0-23.7), respectively. In multivariable analysis, N0M0 patients with ≥4 liver tumours had similar survival as those with N1 disease (adjusted hazard ratio 1.01, 95% CI 0.58-1.75).

Tumour multiplicity in ICC is associated with inferior OS compared with solitary liver tumours, particularly in patients with ≥4 tumours. Future ICC staging systems should consider the prognostic significance of tumour number.

Our research provides critical insights into the prognosis of intrahepatic cholangiocarcinoma (ICC) with multiple liver tumours, highlighting the significant impact of tumour multiplicity on survival outcomes. This work addresses the gap in the current staging system, which does not adequately reflect the poor prognosis associated with multiple tumours, especially with the presence of ≥4 tumours. Incorporating these insights into clinical practice could aid in treatment decision-making, risk stratification, and potentially improve patient care and outcomes in ICC management.