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Time to Rethink Upfront Surgery for Resectable Intrahepatic Cholangiocarcinoma? Implications from the Neoadjuvant Experience

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

Abstract

Background

While surgery is a mainstay of curative-intent treatment for patients with intrahepatic cholangiocarcinoma (IHC), the role of neoadjuvant therapy (NT) has not been well-established. We sought to describe trends in NT utilization, characterize associated factors, and evaluate association with overall survival (OS).

Methods

Retrospective cohort study of 4456 surgically resected IHC patients within National Cancer Data Base (2006–2016). NT included chemotherapy alone and/or (chemo)radiation. Descriptive statistics used to describe the cohort. Multivariable hierarchical logistic regression models were used to examine factors associated with NT administration. Analyses conducted comparing OS among upfront surgery patients and NT patients using propensity matching using nearest-neighbor methodology and adjustment using inverse probability of treatment weighting (IPTW). Association between NT and risk of death evaluated using multivariable Cox shared frailty modeling.

Results

Utilization of NT did not significantly increase over time (11%-2006 to 16%-2016, trend test p = 0.07) but did increase among patients with clinical nodal involvement (cN+, 13% to 36%, p = 0.002). Factors associated with NT use include cN+ disease (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.31–2.15) and advanced clinical T stage: T2 (OR 1.65, 95% CI 1.33–2.06); T3 (OR 1.51, 95% CI 1.13–2.02). After propensity matching, NT associated with a 23% decreased risk of death relative to upfront surgery (hazard ratio [HR] 0.77, 95% CI 0.61–0.97). Findings were similar after IPTW (HR 0.83, 95% CI 0.78–0.88).

Conclusions

NT is increasingly used for the management of IHC patients with characteristics indicating aggressive tumor biology and is associated with decreased risk of death. These data suggest need for prospective studies of NT in management of patients with potentially resectable IHC.

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Acknowledgment

The CoC’s NCDB and the hospitals participating in the CoC’s NCDB are the source of the deidentified data used herein; they have not verified and are not responsible for the statistical validity of the data analysis or the conclusions derived by the authors.

Funding

Coauthor Dr. Massarweh is supported in part by the Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, and the Center for Innovations in Quality, Effectiveness and Safety (CIN 13-413).

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Authors and Affiliations

  1. Hepato-Pancreato-Biliary Section, Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Meredith C. Mason MD, Ching-Wei D. Tzeng MD, Yi-Ju Chiang MSPH, Yun Shin Chun MD, Thomas A. Aloia MD, Jean-Nicolas Vauthey MD & Hop S. Tran Cao MD

  2. Center for Innovations in Quality, Effectiveness and Safety, Michael E. DeBakey VA Medical Center, Houston, TX, USA

    Nader N. Massarweh MD, MPH

  3. Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX, USA

    Nader N. Massarweh MD, MPH

  4. Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX, USA

    Nader N. Massarweh MD, MPH

  5. Department of GI Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Milind Javle MD

Authors
  1. Meredith C. Mason MD
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  2. Nader N. Massarweh MD, MPH
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  3. Ching-Wei D. Tzeng MD
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  4. Yi-Ju Chiang MSPH
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  5. Yun Shin Chun MD
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  6. Thomas A. Aloia MD
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  7. Milind Javle MD
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  8. Jean-Nicolas Vauthey MD
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  9. Hop S. Tran Cao MD
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Contributions

Drs. Tran Cao and Mason conceived of the study concept and design and prepared the manuscript. Ms. Chiang had access to the data and completed all statistical analyses. All authors contributed to the study’s interpretation, review, and manuscript approval.

Corresponding author

Correspondence to Hop S. Tran Cao MD.

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Mason, M.C., Massarweh, N.N., Tzeng, CW.D. et al. Time to Rethink Upfront Surgery for Resectable Intrahepatic Cholangiocarcinoma? Implications from the Neoadjuvant Experience. Ann Surg Oncol 28, 6725–6735 (2021). https://doi.org/10.1245/s10434-020-09536-w

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  • DOI: https://doi.org/10.1245/s10434-020-09536-w

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