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Clinical Studies

Development and external validation of a prediction model for overall survival after resection of distal cholangiocarcinoma

Abstract

Background

Various prognostic factors are associated with overall survival (OS) after resection of distal cholangiocarcinoma (dCCA). The objective of this study was to develop and validate a prediction model for 3-year OS after pancreatoduodenectomy for dCCA.

Methods

The derivation cohort consisted of all patients who underwent pancreatoduodenectomy for dCCA in the Netherlands (2009–2016). Clinically relevant variables were selected based on the Akaike information criterion using a multivariate Cox proportional hazards regression model, with model performance being assessed by concordance index (C-index) and calibration plots. External validation was performed using patients from the Belgium Cancer Registry (2008–2016), and patients from two university hospitals of Southampton (U.K.) and Verona (Italy).

Results

Independent prognostic factors for OS in the derivation cohort of 454 patients after pancreatoduodenectomy for dCCA were age (HR 1.02, 95% CI 1.01–1.03), pT (HR 1.43, 95% CI 1.07–1.90) and pN category (pN1: HR 1.78, 95% CI 1.37–2.32; pN2: HR 2.21, 95% CI 1.63–3.01), resection margin status (HR 1.79, 95% CI 1.39–2.29) and tumour differentiation (HR 2.02, 95% CI 1.62–2.53). The prediction model was based on these prognostic factors. The optimism-adjusted C-indices were similar in the derivation cohort (0.69), and in the Belgian (0.66) and Southampton-Verona (0.68) validation cohorts. Calibration was accurate in the Belgian validation cohort (slope = 0.93, intercept = 0.12), but slightly less optimal in the Southampton-Verona validation cohort (slope = 0.88, intercept = 0.32). Based on this model, three risk groups with different prognoses were identified (3-year OS of 65.4%, 33.2% and 11.8%).

Conclusions

The prediction model for 3-year OS after resection of dCCA had reasonable performance in both the derivation and geographically external validation cohort. Calibration slightly differed between validation cohorts. The model is readily available via www. pancreascalculator.com to inform patients from Western European countries on their prognosis, and may be used to stratify patients for clinical trials.

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Fig. 1: Nomogram for prediction of 1, 2 and 3-year overall survival.
Fig. 2: Three risk groups based on the prediction model score.
Fig. 3: Kaplan–Meier curves by adjuvant chemotherapy for the derivation and validation cohorts, stratified by risk group.

Data availability

Anonymous individual data could be requested from the corresponding author.

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Acknowledgements

This study was conducted on behalf of the Dutch Pancreatic Cancer Group (DPCG).

Funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

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Authors

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Contributions

AB, SR, IB, CV, CP, MB and HK designed the study. AB, SR, CD, LD, A. Balduzzi, A.B.C. and a trained registry administrator from the BCR collected and updated the necessary data. A.B. performed the statistical analyses with support from S.R. and M.O. which were interpreted by all authors. A.B. drafted the manuscript and all authors revised the manuscript and approved the final manuscript for publication.

Corresponding author

Correspondence to Heinz-Josef Klümpen.

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Competing interests

The authors declare no competing interests.

Ethical approval and consent to participate

This study was approved by the Dutch Pancreatic Cancer Group. We received a waiver for ethical approval of this study by the Medical Ethics Review Committee at Amsterdam UMC, location Academic Medical Center (W19_191 # 19.230).

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Belkouz, A., Van Roessel, S., Strijker, M. et al. Development and external validation of a prediction model for overall survival after resection of distal cholangiocarcinoma. Br J Cancer 126, 1280–1288 (2022). https://doi.org/10.1038/s41416-021-01687-1

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  • DOI: https://doi.org/10.1038/s41416-021-01687-1

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