Nationwide Validation of the 8th American Joint Committee on Cancer TNM Staging System and Five Proposed Modifications for Resected Pancreatic Cancer

Annals of Surgical Oncology, vol. 29, pp. 5988–5999

Abstract

BACKGROUND: The prognostic value of four proposed modifications to the 8th American Joint Committee on Cancer (AJCC) TNM staging system has yet to be evaluated. This study aimed to validate five proposed modifications. METHODS: Patients who underwent pancreatic ductal adenocarcinoma resection (2014-2016), as registered in the prospective Dutch Pancreatic Cancer Audit, were included. Stratification and prognostication of TNM staging systems were assessed using Kaplan-Meier curves, Cox proportional hazard analyses, and C-indices. A new modification was composed based on overall survival (OS). RESULTS: Overall, 750 patients with a median OS of 18 months (interquartile range 10-32) were included. The 8th edition had an increased discriminative ability compared with the 7th edition {C-index 0.59 (95% confidence interval [CI] 0.56-0.61) vs. 0.56 (95% CI 0.54-0.58)}. Although the 8th edition showed a stepwise decrease in OS with increasing stage, no differences could be demonstrated between all substages; stage IIA vs. IB (hazard ratio [HR] 1.30, 95% CI 0.80-2.09; p = 0.29) and stage IIB vs. IIA (HR 1.17, 95% CI 0.75-1.83; p = 0.48). The four modifications showed comparable prognostic accuracy (C-index 0.59-0.60); however, OS did not differ between all modified TNM stages (ns). The new modification, migrating T3N1 patients to stage III, showed a C-index of 0.59, but did detect significant survival differences between all TNM stages (p < 0.05). CONCLUSIONS: The 8th TNM staging system still lacks prognostic value for some categories of patients, which was not clearly improved by four previously proposed modifications. The modification suggested in this study allows for better prognostication in patients with all stages of disease.

Authors 30

1. Thijs J. Schouten

   University Medical Center Utrecht · St. Antonius Ziekenhuis

   Affiliation as printed

   Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands

2. Lois A. Daamen

   University Medical Center Utrecht · Utrecht University · St. Antonius Ziekenhuis

   Affiliation as printed

   Department of Radiation Oncology, UMC Utrecht Cancer Center, Utrecht, The Netherlands

   Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands

3. Galina A. Dorland

   University of Amsterdam · University Medical Center Utrecht · Amsterdam University Medical Centers · Cancer Center Amsterdam · St. Antonius Ziekenhuis

   Affiliation as printed

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

   Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands

4. Stijn R. van Roessel

   University of Amsterdam · Amsterdam University Medical Centers · Cancer Center Amsterdam

   Affiliation as printed

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

5. Vincent P. Groot

   University Medical Center Utrecht · St. Antonius Ziekenhuis

   Affiliation as printed

   Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands

6. Marc G. Besselink

   University of Amsterdam · Amsterdam University Medical Centers · Cancer Center Amsterdam

   Affiliation as printed

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

7. Bert A. Bonsing

   Leiden University Medical Center

   Affiliation as printed

   Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands

8. Koop P Bosscha

   Jeroen Bosch Ziekenhuis

   Affiliation as printed

   Department of Surgery, Jeroen Bosch Hospital, Den Bosch, The Netherlands

9. Lodewijk A.A. Brosens

   University Medical Center Utrecht · Utrecht University

   Affiliation as printed

   Department of Pathology, UMC Utrecht Cancer Center, Utrecht, The Netherlands

10. Olivier R. Busch

    University of Amsterdam · Amsterdam University Medical Centers · Cancer Center Amsterdam

    Affiliation as printed

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

11. Ronald M. van Dam Aachen Department of General and Visceral Surgery

    Universitätsklinikum Aachen · Maastricht University · Maastricht University Medical Centre

    Affiliation as printed

    Department of General and Visceral Surgery, University Hospital Aachen, Aachen, Germany

    Department of Surgery, Maastricht UMC+, Maastricht, The Netherlands

    GROW - School for Oncology & Developmental Biology, Maastricht University, Maastricht, The Netherlands

12. Arantza Fariña Sarasqueta

    University of Amsterdam · Amsterdam University Medical Centers · Cancer Center Amsterdam · Leiden University Medical Center · Amsterdam UMC Location University of Amsterdam

    Affiliation as printed

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

    Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands

13. Sebastiaan Festen

    OLVG

    Affiliation as printed

    Department of Surgery, OLVG, Amsterdam, The Netherlands

14. Bas Groot Koerkamp

    Erasmus MC

    Affiliation as printed

    Department of Surgery, Erasmus MC, Rotterdam, The Netherlands

15. Erwin van der Harst

    Maasstad Ziekenhuis

    Affiliation as printed

    Department of Surgery, Maasstad Hospital, Rotterdam, The Netherlands

16. Ignace H. J. T. de Hingh

    Maastricht University · Catharina Ziekenhuis

    Affiliation as printed

    Department of Surgery, Catharina Hospital, Eindhoven, The Netherlands

    GROW - School for Oncology & Developmental Biology, Maastricht University, Maastricht, The Netherlands

17. Martijn Intven

    University Medical Center Utrecht · Utrecht University

    Affiliation as printed

    Department of Radiation Oncology, UMC Utrecht Cancer Center, Utrecht, The Netherlands

18. Geert Kazemier

    Amsterdam University Medical Centers · Amsterdam UMC Location Vrije Universiteit Amsterdam · Cancer Center Amsterdam

    Affiliation as printed

    Department of Surgery, Cancer Center Amsterdam, Amsterdam UMC, VU Medical Center, Amsterdam, The Netherlands

19. Vincent Erwin de Meijer

    University Medical Center Groningen

    Affiliation as printed

    Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands

20. Vincent B. Nieuwenhuijs

    Isala

    Affiliation as printed

    Department of Surgery, Isala, Zwolle, The Netherlands

21. G. Mihaela Raicu

    St. Antonius Ziekenhuis

    Affiliation as printed

    Department of Pathology, St. Antonius Hospital, Nieuwegein, The Netherlands

22. Daphne Roos

    Reinier de Graaf Hospital

    Affiliation as printed

    Department of Surgery, Reinier de Graaf Group, Delft, The Netherlands

23. Jennifer M. J. Schreinemakers

    Amphia Ziekenhuis

    Affiliation as printed

    Department of Surgery, Amphia Hospital, Breda, The Netherlands

24. Martijn W.J. Stommel

    Radboud University Medical Center

    Affiliation as printed

    Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands

25. Marie‐Louise F. van Velthuysen

    Erasmus MC

    Affiliation as printed

    Department of Pathology, Erasmus MC, Rotterdam, Netherlands

26. Robert C. Verdonk

    University Medical Center Utrecht · St. Antonius Ziekenhuis

    Affiliation as printed

    Department of Gastroenterology, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands

27. Joanne Verheij

    University of Amsterdam · Amsterdam University Medical Centers · Cancer Center Amsterdam · Amsterdam UMC Location University of Amsterdam

    Affiliation as printed

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

28. Helena Marieke Verkooijen

    University Medical Center Utrecht · Utrecht University

    Affiliation as printed

    Imaging Division, University Medical Center Utrecht, Utrecht, The Netherlands

    Utrecht University, Utrecht, The Netherlands

29. Hjalmar C. van Santvoort

    University Medical Center Utrecht · St. Antonius Ziekenhuis

    Affiliation as printed

    Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands

30. Izaak Quintus Molenaar corresponding

    University Medical Center Utrecht · St. Antonius Ziekenhuis

    Affiliation as printed

    Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands. I.Q.Molenaar@umcutrecht.nl

    Department of Surgery, Regional Academic Cancer Center Utrecht, UMC Utrecht Cancer Center & St. Antonius Hospital Nieuwegein, Utrecht, The Netherlands