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Clinical Studies

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



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.


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).


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%).


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. 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.


  1. Rizvi S, Khan SA, Hallemeier CL, Kelley RK, Gores GJ. Cholangiocarcinoma—evolving concepts and therapeutic strategies. Nat Rev Clin Oncol. 2018;15:95–111.

    CAS  Article  Google Scholar 

  2. Razumilava N, Gores GJ. Classification, diagnosis, and management of cholangiocarcinoma. Clin Gastroenterol Hepatol. 2013;11:13–21 e11.

    Article  Google Scholar 

  3. Roos E, Strijker M, Franken LC, Busch OR, van Hooft JE, Klumpen HJ, et al. Comparison of short- and long-term outcomes between anatomical subtypes of resected biliary tract cancer in a Western high-volume center. HPB (Oxf). 2020;22:405–14.

    Article  Google Scholar 

  4. Zhou Y, Liu S, Wu L, Wan T. Survival after surgical resection of distal cholangiocarcinoma: a systematic review and meta-analysis of prognostic factors. Asian J Surg. 2017;40:129–38.

    CAS  Article  Google Scholar 

  5. Byrling J, Andersson R, Sasor A, Lindell G, Ansari D, Nilsson J, et al. Outcome and evaluation of prognostic factors after pancreaticoduodenectomy for distal cholangiocarcinoma. Ann Gastroenterol. 2017;30:571–7.

    PubMed  PubMed Central  Google Scholar 

  6. Wellner UF, Shen Y, Keck T, Jin W, Xu Z. The survival outcome and prognostic factors for distal cholangiocarcinoma following surgical resection: a meta-analysis for the 5-year survival. Surg Today. 2017;47:271–9.

    CAS  Article  Google Scholar 

  7. Belkouz A, Wilmink JW, Haj Mohammad N, Hagendoorn J, de Vos-Geelen J, Dejong CHC, et al. Advances in adjuvant therapy of biliary tract cancer: an overview of current clinical evidence based on phase II and III trials. Crit Rev Oncol Hematol. 2020;151:102975.

    CAS  Article  Google Scholar 

  8. Shroff RT, Kennedy EB, Bachini M, Bekaii-Saab T, Crane C, Edeline J, et al. Adjuvant therapy for resected biliary tract cancer: ASCO Clinical Practice Guideline. J Clin Oncol. 2019;37:1015–27.

    Article  Google Scholar 

  9. Primrose JN, Fox RP, Palmer DH, Malik HZ, Prasad R, Mirza D, et al. Capecitabine compared with observation in resected biliary tract cancer (BILCAP): a randomised, controlled, multicentre, phase 3 study. Lancet Oncol. 2019;20:663–73.

    CAS  Article  Google Scholar 

  10. Groot Koerkamp B, Wiggers JK, Gonen M, Doussot A, Allen PJ, Besselink MGH, et al. Survival after resection of perihilar cholangiocarcinoma-development and external validation of a prognostic nomogram. Ann Oncol. 2015;26:1930–5.

    CAS  Article  Google Scholar 

  11. Hyder O, Marques H, Pulitano C, Marsh JW, Alexandrescu S, Bauer TW, et al. A nomogram to predict long-term survival after resection for intrahepatic cholangiocarcinoma: an Eastern and Western experience. JAMA Surg. 2014;149:432–8.

    Article  Google Scholar 

  12. Moons KGM, Wolff RF, Riley RD, Whiting PF, Westwood M, Collins GS, et al. PROBAST: A tool to assess risk of bias and applicability of prediction model studies: explanation and elaboration. Ann Intern Med. 2019;170:W1–W33.

    Article  Google Scholar 

  13. Collins GS, Reitsma JB, Altman DG, Moons KG. Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD): the TRIPOD statement. Ann Intern Med. 2015;162:55–63.

    Article  Google Scholar 

  14. Strijker M, Belkouz A, van der Geest LG, van Gulik TM, van Hooft JE, de Meijer VE, et al. Treatment and survival of resected and unresected distal cholangiocarcinoma: a nationwide study. Acta Oncol. 2019;58:1048–55.

    Article  Google Scholar 

  15. Frosio F, Mocchegiani F, Conte G, Bona ED, Vecchi A, Nicolini D, et al. Neoadjuvant therapy in the treatment of hilar cholangiocarcinoma: review of the literature. World J Gastrointest Surg. 2019;11:279–86.

    Article  Google Scholar 

  16. Seita K, Ebata T, Mizuno T, Maeda A, Yamaguchi R, Kurumiya Y, et al. Phase 2 trial of adjuvant chemotherapy with S - 1 for node-positive biliary tract cancer (N-SOG 09). Ann Surg Oncol. 2020;27:2348–56.

    Article  Google Scholar 

  17. Ebata T, Hirano S, Konishi M, Uesaka K, Tsuchiya Y, Ohtsuka M, et al. Randomized clinical trial of adjuvant gemcitabine chemotherapy versus observation in resected bile duct cancer. Br J Surg. 2018;105:192–202.

    CAS  Article  Google Scholar 

  18. Edeline J, Benabdelghani M, Bertaut A, Watelet J, Hammel P, Joly JP, et al. Gemcitabine and oxaliplatin chemotherapy or surveillance in resected biliary tract cancer (PRODIGE 12-ACCORD 18-UNICANCER GI): a randomized phase III study. J Clin Oncol. 2019;37:658–67.

    CAS  Article  Google Scholar 

  19. Nakachi K, Konishi M, Ikeda M, Mizusawa J, Eba J, Okusaka T, et al. A randomized Phase III trial of adjuvant S-1 therapy vs. observation alone in resected biliary tract cancer: Japan Clinical Oncology Group Study (JCOG1202, ASCOT). Jpn J Clin Oncol. 2018;48:392–5.

    Article  Google Scholar 

  20. Stein A, Arnold D, Bridgewater J, Goldstein D, Jensen LH, Klumpen HJ, et al. Adjuvant chemotherapy with gemcitabine and cisplatin compared to observation after curative intent resection of cholangiocarcinoma and muscle invasive gallbladder carcinoma (ACTICCA-1 trial)—a randomized, multidisciplinary, multinational phase III trial. BMC Cancer. 2015;15:564.

    Article  Google Scholar 

  21. Moon A, Choi DW, Choi SH, Heo JS, Jang KT. Validation of T stage according to depth of invasion and N stage subclassification based on number of metastatic lymph nodes for distal extrahepatic bile duct (EBD) carcinoma. Medicine (Baltim). 2015;94:e2064.

    Article  Google Scholar 

  22. Postlewait LM, Ethun CG, Le N, Pawlik TM, Buettner S, Poultsides G, et al. Proposal for a new T-stage classification system for distal cholangiocarcinoma: a 10-institution study from the U.S. Extrahepatic Biliary Malignancy Consortium. HPB (Oxf). 2016;18:793–9.

    Article  Google Scholar 

  23. Li X, Lin H, Sun Y, Gong J, Feng H, Tu J. Prognostic significance of the lymph node ratio in surgical patients with distal cholangiocarcinoma. J Surg Res. 2019;236:2–11.

    Article  Google Scholar 

  24. Gottlieb-Vedi E, Mattsson F, Lagergren P, Lagergren J. Annual hospital volume of surgery for gastrointestinal cancer in relation to prognosis. Eur J Surg Oncol. 2019;45:1839–46.

    Article  Google Scholar 

  25. Komaya K, Ebata T, Shirai K, Ohira S, Morofuji N, Akutagawa A, et al. Recurrence after resection with curative intent for distal cholangiocarcinoma. Br J Surg. 2017;104:426–33.

    CAS  Article  Google Scholar 

  26. Strijker M, Chen JW, Mungroop TH, Jamieson NB, van Eijck CH, Steyerberg EW, et al. Systematic review of clinical prediction models for survival after surgery for resectable pancreatic cancer. Br J Surg. 2019;106:342–54.

    CAS  Article  Google Scholar 

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


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 and Affiliations




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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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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This manuscript does not contain any individual person’s data in any form.

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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).

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