*Purpose: Preliminary single-center data suggest multimodal therapy may improve outcomes for patients with intrahepatic cholangiocarcinoma (iCCA) undergoing liver transplant (LT), particularly in the setting of stable disease. However, despite recent advances, iCCA remains a contraindication to LT due to historically poor survival and high recurrence rates. The present study harnessed the power of the Surveillance, Epidemiology, and End Results (SEER) dataset to evaluate the efficacy of multimodal therapy in patients with liver-limited, locally advanced iCCA who would be potential candidates for LT.

*Methods: The SEER database was queried for patients with iCCA from 2004-2014. Only patients eligible for transplant (negative nodal status, no extrahepatic disease) were considered.

*Results: 1621 patients with liver-limited and/or locally advanced iCCA were identified. Median survival with surgery alone or surgery+medical therapy was 46mo, compared with 5mo for no treatment and 13mo for medical therapy. LT+medical therapy offered the best survival, with median survival >60mo (62% at 5yrs). This advantage persisted in subgroup analysis comparing patients with cumulative tumor diameter <5cm (Figure 1) and those with well-to-moderately differentiated disease (Figure 2). On multivariate cox proportional hazard analysis, age >70 [HR=1.7,p=0.01], size >7cm [HR=1.85,p=0.04] and stage (>T1 [HR=1.4,p=0.03], >T2 [HR=1.9,p<0.0001]) significantly increased the risk of mortality.

*Conclusions: Liver-limited and/or locally advanced intrahepatic cholangiocarcinoma carries a poor prognosis, and survival is limited in the absence of surgery. LT plus neoadjuvant therapy improves patient survival in this cohort and may be a viable alternative for otherwise unresectable disease. Prospective clinical trials are critical to further establish the role of LT in the management of iCCA.

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