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

  • Hepatobiliary Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

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.

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Author information

Authors and Affiliations

  1. Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA

    Laura Alaimo MD, Zorays Moazzam MD, Yutaka Endo MD, PhD, Henrique A. Lima MD & Timothy M. Pawlik MD, PhD, MPH, MTS, MBA, FACS, FRACS (Hon.)

  2. Department of Surgery, University of Verona, Verona, Italy

    Laura Alaimo MD, Andrea Ruzzenente MD, PhD & Alfredo Guglielmi MD

  3. Department of Surgery, Ospedale San Raffaele, Milan, Italy

    Luca Aldrighetti MD

  4. Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA

    Matthew Weiss MD

  5. Department of Surgery, University of Virginia, Charlottesville, VA, USA

    Todd W. Bauer MD

  6. Department of Surgery, Fundeni Clinical Institute, Bucharest, Romania

    Sorin Alexandrescu MD

  7. Department of Surgery, Stanford University, Stanford, CA, USA

    George A. Poultsides MD

  8. Department of Surgery, Emory University, Atlanta, GA, USA

    Shishir K. Maithel MD

  9. Department of Surgery, Curry Cabral Hospital, Lisbon, Portugal

    Hugo P. Marques MD

  10. Department of Surgery, University of Ottawa, Ottawa, ON, Canada

    Guillaume Martel MD

  11. Department of Surgery, Royal Prince Alfred Hospital, University of Sydney, Sydney, NSW, Australia

    Carlo Pulitano MD

  12. Department of Surgery, Eastern Hepatobiliary Surgery Hospital, Shanghai, China

    Feng Shen MD

  13. Department of Hepatobiliopancreatic Surgery and Liver Transplantation, AP-HP, Beaujon Hospital, Clichy, France

    François Cauchy MD

  14. Department of Surgery, Erasmus University Medical Centre, Rotterdam, The Netherlands

    Bas Groot Koerkamp MD

  15. Department of Gastroenterological Surgery, Yokohama City University School of Medicine, Yokohama, Japan

    Itaru Endo MD, PhD

  16. Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA

    Timothy M. Pawlik MD, PhD, MPH, MTS, MBA, FACS, FRACS (Hon.)

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  1. Laura Alaimo MD
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  2. Zorays Moazzam MD
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  20. Timothy M. Pawlik MD, PhD, MPH, MTS, MBA, FACS, FRACS (Hon.)
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Corresponding author

Correspondence to Timothy M. Pawlik MD, PhD, MPH, MTS, MBA, FACS, FRACS (Hon.).

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Supplementary Information

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10434_2022_12795_MOESM1_ESM.tiff

Supplementary Figure S1. Multiple density plots of overall survival stratified by T-category.a, Overall survival for the entire cohort. b, Overall survival for Common ICC. c, Overall survival for Proliferative ICC. d, Overall survival for Inflammatory ICC. OS, overall survival (months after surgery). (TIFF 5659 KB)

10434_2022_12795_MOESM2_ESM.tiff

Supplementary Figure S2. Multiple density plots of overall survival stratified by N-category.a, Overall survival for the entire cohort. b, Overall survival for Common ICC. c, Overall survival for Proliferative ICC. d, Overall survival for Inflammatory ICC. OS, overall survival (months after surgery). (TIFF 5659 KB)

Supplementary file3 (DOCX 16 KB)

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Alaimo, L., Moazzam, Z., Endo, Y. et al. Long-Term Recurrence-Free and Overall Survival Differ Based on Common, Proliferative, and Inflammatory Subtypes After Resection of Intrahepatic Cholangiocarcinoma. Ann Surg Oncol 30, 1392–1403 (2023). https://doi.org/10.1245/s10434-022-12795-4

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