Long-Term Recurrence-Free and Overall Survival Differ Based on Common, Proliferative, and Inflammatory Subtypes After Resection of Intrahepatic Cholangiocarcinoma

Laura Alaimo, Zorays Moazzam, Yutaka Endo, Henrique A Lima, Andrea Ruzzenente, Alfredo Guglielmi, Luca Aldrighetti, Matthew Weiss, Todd W Bauer, Sorin Alexandrescu, George A Poultsides, Shishir K Maithel, Hugo P Marques, Guillaume Martel, Carlo Pulitano, Feng Shen, François Cauchy, Bas Groot Koerkamp, Itaru Endo, Timothy M Pawlik

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)


INTRODUCTION: While generally associated with poor prognosis, intrahepatic cholangiocarcinoma (ICC) can have a heterogeneous presentation and natural history. We sought to identify specific ICC subtypes that may be associated with varied long-term outcomes and patterns of recurrence after liver resection.

METHODS: Patients who underwent curative-intent resection for ICC from 2000 to 2020 were identified from a multi-institutional database. Hierarchical cluster analysis characterized three ICC subtypes based on morphology (i.e., tumor burden score [TBS]) and biology (i.e., preoperative neutrophil-to-lymphocyte ratio [NLR] and CA19-9 levels).

RESULTS: Among 598 patients, the cluster analysis identified three ICC subtypes: Common (n = 300, 50.2%) (median, TBS: 4.5; NLR: 2.4; CA19-9: 38.0 U/mL); Proliferative (n = 246, 41.1%) (median, TBS: 8.8; NLR: 2.9; CA19-9: 71.2 U/mL); Inflammatory (n = 52, 8.7%) (median, TBS: 5.4; NLR: 12.6; CA19-9: 26.7 U/mL). Median overall survival (OS) (Common: 72.0 months; Proliferative: 31.4 months; Inflammatory: 22.9 months) and recurrence-free survival (RFS) (Common: 21.5 months; Proliferative: 11.9 months; Inflammatory: 9.0 months) varied considerably among the different ICC subtypes (all p < 0.001). Even though patients with Inflammatory ICC had more favorable T-(T1/T2, Common: 84.4%; Proliferative: 80.6%; Inflammatory: 86.5%) and N-(N0, Common: 14.0%; Proliferative: 20.7%; Inflammatory: 26.9%) disease, the Inflammatory subtype was associated with a higher incidence of intra- and extrahepatic recurrence (Common: 15.8%; Proliferative: 24.2%; Inflammatory: 28.6%) (all p = 0.01).

CONCLUSIONS: Cluster analysis identified three distinct subtypes of ICC based on TBS, NLR, and CA19-9. ICC subtype was associated with RFS and OS and predicted worse outcomes among patients. Despite more favorable T- and N-disease, the Inflammatory ICC subtype was associated with worse outcomes ICC subtype should be considered in the prognostic stratification of patients.

Original languageEnglish
Pages (from-to)1392-1403
Number of pages12
JournalAnnals of Surgical Oncology
Issue number3
Early online dateNov 2022
Publication statusPublished - Mar 2023

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© 2022, Society of Surgical Oncology.


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