Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Clinical Studies

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

British Journal of Cancer volume 126, pages 1280–1288 (2022)Cite this article

Subjects

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others

Data availability

Anonymous individual data could be requested from the corresponding author.

References

  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.

    Article  CAS  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.

    Article  CAS  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.

    Article  CAS  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.

    Article  CAS  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.

    Article  CAS  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.

    Article  CAS  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.

    Article  CAS  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.

    Article  CAS  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.

    Article  CAS  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.

    Article  CAS  Google Scholar 

Download references

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.

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

    Ali Belkouz, Martijn G. H. van Oijen, Cornelis J. A. Punt & Heinz-Josef Klümpen

  2. Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

    Stijn Van Roessel, Marin Strijker, Susan van Dieren & Marc G. Besselink

  3. Department of Surgery, Erasmus MC Cancer Institute, Rotterdam, The Netherlands

    Jacob L. van Dam & Bas Groot Koerkamp

  4. Department of Surgery, University Medical Center Utrecht, Utrecht, The Netherlands

    Lois Daamen & Quintus Molenaar

  5. Department of research, Netherlands Comprehensive Cancer Organization (IKNL), Utrecht, The Netherlands

    Lydia G. van der Geest

  6. Department of General and Pancreatic Surgery, Integrated University Hospital of Verona, Verona, Italy

    Alberto Balduzzi & Giuseppe Malleo

  7. Department of Surgery, University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom

    Andrea Benedetti Cacciaguerra & Mohammed Abu Hilal

  8. Department of Pathology, Cancer Center Amsterdam, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands

    Joanne Verheij

  9. Research Department, Belgian Cancer Registry, Brussels, Belgium

    Elizabeth Van Eycken

  10. Department of Gastroenterology and Hepatology, University Hospitals St-Luc, Brussels, Belgium

    Ivan Borbath

  11. Department of Gastroenterology/Digestive Oncology, University Hospitals Gasthuisberg/Leuven & KULeuven, Leuven, Belgium

    Chris Verslype

Authors
  1. Ali Belkouz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Stijn Van Roessel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marin Strijker
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jacob L. van Dam
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lois Daamen
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Lydia G. van der Geest
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Alberto Balduzzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Andrea Benedetti Cacciaguerra
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Susan van Dieren
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Quintus Molenaar
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Bas Groot Koerkamp
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Joanne Verheij
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Elizabeth Van Eycken
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Giuseppe Malleo
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Mohammed Abu Hilal
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Martijn G. H. van Oijen
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Ivan Borbath
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Chris Verslype
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Cornelis J. A. Punt
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Marc G. Besselink
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Heinz-Josef Klümpen
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

Dutch Pancreatic Cancer Group (DPCG)

  • Quintus Molenaar
  • , Bas Groot Koerkamp
  • , Joanne Verheij
  •  & Marc G. Besselink

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.

Ethics declarations

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).

Consent to publish

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

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

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

This article is cited by

Search

Advanced search

Quick links