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Neoadjuvant Chemotherapy for Intrahepatic Cholangiocarcinoma: A Propensity Score Survival Analysis Supporting Use in Patients with High-Risk Disease

  • Global Health Services Research
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Abstract

Background

Upfront surgery is the current standard for resectable intrahepatic cholangiocarcinoma (ICC) despite high treatment failure with this approach. We sought to examine the use of neoadjuvant chemotherapy (NAC) as an alternative strategy for this population.

Methods

The National Cancer Database was used to identify patients with resectable ICC undergoing curative-intent surgery (2006–2014). Utilization trends were examined and survival estimates between NAC and upfront surgery were compared; propensity score-matched models were used to examine the association of NAC with overall survival (OS) for all patients and risk-stratified cohorts. Models accounted for clustering within hospitals, and results represent findings from a complete-case analysis.

Results

Among 881 patients with ICC, 8.3% received NAC, with no changes over time (Cochran–Armitage p = 0.7). Median follow-up was 50.9 months, with no difference in unadjusted survival with NAC versus upfront surgery (median OS 51.8 vs. 35.6 months, and 5-year OS rates of 38.2% vs. 36.6%; log rank p = 0.51), and no survival benefit in the propensity score-matched analysis (hazard ratio [HR] 0.78, 95% CI 0.54–1.11; p = 0.16). However, for patients with stage II–III disease, NAC was associated with a trend towards improved survival (median OS of 47.6 months vs. 25.9 months, and 5-year OS rates of 34% vs. 25.7%; log-rank p = 0.10) and a statistically significant survival benefit in the propensity score-matched analysis. (HR 0.58, 95% CI 0.37–0.91; p = 0.02).

Conclusion

NAC is associated with improved OS over upfront surgery in patients with resectable ICC and high-risk of treatment failure. These data support the need for prospective studies to examine NAC as an alternative strategy to improve OS in this population.

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Acknowledgment

The data used in this study are derived from a de-identified NCDB file. The American College of Surgeons and the CoC have not verified and are not responsible for the analytic or statistical methodology employed, or the conclusions drawn from these data by the investigator. The authors would like to thank Ms. Diana Castillo for her assistance with manuscript preparation and formatting, and creation of the figures.

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Authors and Affiliations

  1. Section of Hepatobiliary Tumors, Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Ovie Utuama MD, PhD, Jennifer B. Permuth MS, PhD, Jason Denbo MD, Richard Kim MD, Jason B. Fleming MD & Daniel A. Anaya MD

  2. School of Public Health, University of South Florida, Tampa, FL, USA

    Ovie Utuama MD, PhD, Getachew Dagne PhD, Aurora Sanchez-Anguiano PhD & Amy Alman PhD

  3. Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

    Jennifer B. Permuth MS, PhD

  4. USF Health Program for Comparative Effectiveness Research and Evidence-Based Medicine, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL, USA

    Ambuj Kumar MD, MPH

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  1. Ovie Utuama MD, PhD
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Correspondence to Daniel A. Anaya MD.

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Utuama, O., Permuth, J.B., Dagne, G. et al. Neoadjuvant Chemotherapy for Intrahepatic Cholangiocarcinoma: A Propensity Score Survival Analysis Supporting Use in Patients with High-Risk Disease. Ann Surg Oncol 28, 1939–1949 (2021). https://doi.org/10.1245/s10434-020-09478-3

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