DaBlaCa-17: nationwide observational study in Denmark on survival before and after implementation of neoadjuvant chemotherapy prior to cystectomy for muscle-invasive bladder cancer

Authors

  • Stefanie Korsgaard Körner Department of Urology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
  • Thomas Dreyer Department of Urology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
  • Andreas Carus Department of Oncology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark
  • Line Hammer Dohn Department of Oncology, Herlev and Gentofte University Hospital, Copenhagen, Denmark
  • Ulla Nordström Joensen Department of Urology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark; Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark
  • Gitte Wrist Lam Department of Urology, Herlev and Gentofte University Hospital, Copenhagen, Denmark
  • Niels Viggo Jensen Department of Oncology, Odense University Hospital, Odense, Denmark
  • Knud Fabrin Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; Department of Urology, Aalborg University Hospital, Aalborg, Denmark
  • Thor Knak Jensen Department of Urology, Odense University Hospital, Odense, Denmark
  • Helle Pappot Department of Clinical Medicine, Copenhagen University, Copenhagen, Denmark; Department of Oncology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
  • Mads Agerbæk Department of Oncology, Aarhus University Hospital, Aarhus, Denmark
  • Jørgen Bjerggaard Jensen Department of Urology, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark

DOI:

https://doi.org/10.2340/sju.v59.24024

Keywords:

Bladder cancer, Cystectomy, Oncological outcomes, Muscle-invasive, Neoadjuvant chemotherapy, survival

Abstract

Objective: To investigate the impact of neoadjuvant chemotherapy implementation with gemcitabine-cisplatin on survival outcomes for patients with muscle-invasive bladder cancer in Denmark.

Materials and Methods: Data were collected on all patients in Denmark undergoing radical cystectomy who were potential candidates for neoadjuvant chemotherapy from 2010 to 2015 (n = 851). A cohort before the implementation of neoadjuvant chemotherapy (Cohort 2010–12) was compared with a cohort after implementation (Cohort 2013–15). Patients in Cohort 2013–15 receiving neoadjuvant chemotherapy (+NAC, n = 213) were compared with patients in Cohort 2013–15 not receiving neoadjuvant chemotherapy (-NAC, n = 139). Pathological results after radical cystectomy and oncological outcomes were compared between the study cohorts. Overall survival, disease-free survival, and disease-specific survival were compared with Kaplan-Meier plots and with univariable and multivariable Cox regression. Kaplan-Meier estimates of overall survival were also performed separately for treating hospital and for pathological stage.

Results: Pathological T0 (pT0) was more frequent in patients who received neoadjuvant chemotherapy: 34% versus 18% when comparing Cohort 2013–15 with Cohort 2010–12 (p < 0.001), and 46% versus 16% in +NAC compared with -NAC (p < 0.001). Overall survival, disease-free survival, and disease-specific survival at 5 years after cystectomy were not improved in Cohort 2013–15 compared with Cohort 2010–12 with adjusted hazard ratios of 1.11 (95% confidence interval [CI]: 0.87–1.43), 1.02 (95% CI: 0.81–1.29), and 1.06 (95% CI: 0.80–1.41), respectively.

Conclusions: This observational study found no improved survival in a national cohort of patients with muscle-invasive bladder cancer undergoing radical cystectomy after implementation of NAC. However, reservations should be made regarding the study design and the true effect of NAC on survival outcomes.

Downloads

Download data is not yet available.

Author Biography

Andreas Carus, Department of Oncology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

Department of Clinical Medicine, Aalborg University, Aalborg, Denmark

References

Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003;349(9):859–866.

https://doi.org/10.1056/NEJMoa022148 DOI: https://doi.org/10.1056/NEJMoa022148

Sherif A, Holmberg L, Rintala E, et al. Neoadjuvant cisplatinum based combination chemotherapy in patients with invasive bladder cancer: a combined analysis of two Nordic studies. Eur Urol. 2004;45(3):297–303.

https://doi.org/10.1016/j.eururo.2003.09.019 DOI: https://doi.org/10.1016/j.eururo.2003.09.019

International Phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol. 2011;29(16):2171–2177.

https://doi.org/10.1200/JCO.2010.32.3139 DOI: https://doi.org/10.1200/JCO.2010.32.3139

Witjes JA, Bruins HM, Cathomas R, et al. European Association of Urology Guidelines on muscle-invasive and metastatic bladder cancer: sum-mary of the 2020 guidelines. Eur Urol. 2021;79(1):82–104.

https://doi.org/10.1016/j.eururo.2020.03.055

Nguyen DP, Thalmann GN. Contemporary update on neoadjuvant therapy for bladder cancer. Nat Rev Urol. 2017;14(6):348–358.

https://doi.org/10.1038/nrurol.2017.30 DOI: https://doi.org/10.1038/nrurol.2017.30

Galsky MD, Hahn NM, Rosenberg J, et al. Treatment of patients with metastatic urothelial cancer ‘Unfit’ for Cisplatin-based chemotherapy. J Clin Oncol. 2011;29(17):2432–2438.

https://doi.org/10.1200/JCO.2011.34.8433 DOI: https://doi.org/10.1200/JCO.2011.34.8433

DaBlaCa. Nationale kliniske retningslinier for behandling af blæretumorer i Danmark. [Cited 0 Nov. 2021] Available from: http://skejby.net/Webudgaven/Pdf/DaBlaCa_april_2016.pdf

DaBlaCa. Kliniske retningslinjer, behandling og opfølgning af muskelinvasiv blærekræft (in Danish) 2020 [updated 2021 Oct 29]. [Cited 14 Nov. 2023] Available from: https://www.dmcg.dk/siteassets/kliniske-retningslinjer---skabeloner-og-vejledninger/kliniske-retningslinjer-opdelt-pa-dmcg/blarecancer/dablaca_muskelinvasiv_1_1_admgodk111120.pdf

Rosenblatt R, Sherif A, Rintala E, et al. Pathologic downstaging is a surrogate marker for efficacy and increased survival following neoadjuvant chemotherapy and radical cystectomy for muscle-invasive urothelial bladder cancer. Eur Urol. 2012;61(6):1229–1238.

https://doi.org/10.1016/j.eururo.2011.12.010 DOI: https://doi.org/10.1016/j.eururo.2011.12.010

Petrelli F, Coinu A, Cabiddu M, et al. Correlation of pathologic complete response with survival after neoadjuvant chemotherapy in bladder cancer treated with cystectomy: a meta-analysis. Eur Urol. 2014;65(2):350–357.

https://doi.org/10.1016/j.eururo.2013.06.049 DOI: https://doi.org/10.1016/j.eururo.2013.06.049

Körner SK, Jensen JB. A population-based retrospective analysis on variation in use of neoadjuvant chemotherapy depending on comorbidity in patients with muscle-invasive bladder cancer undergoing cystectomy in Denmark in the period 2013–2019. Scand J Urol. 2021; 56(1): 34–38.

https://doi.org/10.1080/21681805.2021.2002400 DOI: https://doi.org/10.1080/21681805.2021.2002400

Booth CM, Tannock IF. Randomised controlled trials and population-based observational research: partners in the evolution of medical evidence. Br J Cancer. 2014;110(3):551–555.

https://doi.org/10.1038/bjc.2013.725 DOI: https://doi.org/10.1038/bjc.2013.725

Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med. 2009;150(9):604–612.

https://doi.org/10.7326/0003-4819-150-9-200905050-00006 DOI: https://doi.org/10.7326/0003-4819-150-9-200905050-00006

R Core Team. R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing; 2020.

De Vocht F, Katikireddi SV, McQuire C, et al. Conceptualising natural and quasi experiments in public health. BMC Med Res Methodol. 2021;21(1):32.

https://doi.org/10.1186/s12874-021-01224-x DOI: https://doi.org/10.1186/s12874-021-01224-x

Jensen JB, Ulhøi BP, Jensen KM-E. Extended versus limited lymph node dissection in radical cystectomy: impact on recurrence pattern and sur-vival. Int J Urol. 2012;19(1):39–47.

https://doi.org/10.1111/j.1442-2042.2011.02887.x DOI: https://doi.org/10.1111/j.1442-2042.2011.02887.x

Nakagawa T. Lymph node dissection for bladder cancer: current standards and the latest evidence. Int J Urol. 2021;28(1):7–15.

https://doi.org/10.1111/iju.14398 DOI: https://doi.org/10.1111/iju.14398

Yin M, Joshi M, Meijer RP, et al. Neoadjuvant chemotherapy for muscle-invasive bladder cancer: a systematic review and two-step meta-analysis. Oncologist. 2016;21(6):708–715.

https://doi.org/10.1634/theoncologist.2015-0440 DOI: https://doi.org/10.1634/theoncologist.2015-0440

Hanna N, Trinh QD, Seisen T, et al. Effectiveness of neoadjuvant chemotherapy for muscle-invasive bladder cancer in the current real world setting in the USA. Eur Urol Oncol. 2018;1(1):83–90.

https://doi.org/10.1016/j.euo.2018.03.001 DOI: https://doi.org/10.1016/j.euo.2018.03.001

Russell B, Sherif A, Häggström C, et al. Neoadjuvant chemotherapy for muscle invasive bladder cancer: a nationwide investigation on survival. Scand J Urol. 2019;53(4):206–212.

https://doi.org/10.1080/21681805.2019.1624611 DOI: https://doi.org/10.1080/21681805.2019.1624611

Møller CT, Støer NC, Blindheim A, et al. Downstaging and survival after Neoadjuvant chemotherapy for bladder cancer in Norway; a population-based study. BMC Cancer. 2022;22(1):1301.

https://doi.org/10.1186/s12885-022-10394-w DOI: https://doi.org/10.1186/s12885-022-10394-w

Mitra AP, Cai J, Miranda G, et al. Management trends and outcomes of patients undergoing radical cystectomy for urothelial carcinoma of the bladder: evolution of the University of Southern California experience over 3,347 cases. J Urol. 2022;207(2):302–313.

https://doi.org/10.1097/JU.0000000000002242 DOI: https://doi.org/10.1097/JU.0000000000002242

Witjes JA, Bruins HM, Cathomas R, et al. European Association of Urology Guidelines on Muscle-invasive and Metastatic Bladder Cancer: Sum-mary of the 2020 Guidelines. Eur Urol. 2021;79(1):82-104.

https://doi.org/10.1016/j.eururo.2020.03.055 DOI: https://doi.org/10.1016/j.eururo.2020.03.055

MRC/EORTC. Neoadjuvant cisplatin,methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: a randomised controlled trial. Lancet. 1999;354(9178):533–540.

https://doi.org/10.1016/S0140-6736(99)02292-8 DOI: https://doi.org/10.1016/S0140-6736(99)02292-8

Pfister C, Gravis G, Flechon A, et al. Multicenter randomized phase III trial of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC) as perioperative chemotherapy for muscle-invasive bladder cancer (MIBC): Overall survival (OS) data at 5 years in the GETUG/AFU V05 VESOER trial. JouJ Clin Oncol. 2023;41(17_suppl):LBA4507-LBA. DOI: https://doi.org/10.1200/JCO.2023.41.17_suppl.LBA4507

Pfister C, Gravis G, Fléchon A, et al. Randomized phase III trial of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin, or gemcita-bine and cisplatin as perioperative chemotherapy for patients with muscle-invasive bladder cancer. Analysis of the GETUG/AFU V05 VESPER trial secondary endpoints: chemotherapy toxicity and pathological responses. Eur Urol. 2021;79(2):214–221.

https://doi.org/10.1016/j.eururo.2020.08.024 DOI: https://doi.org/10.1016/j.eururo.2020.08.024

Holmsten K, Omland L, Als A, et al. Implications for efficacy and safety of total dose and dose-intensity of neoadjuvant gemcitabine-cisplatin in muscle-invasive bladder cancer: three-week versus four-week regimen. Bladder Cancer. 2021;8(1):71–80. DOI: https://doi.org/10.3233/BLC-211556

Nielsen N, Wrist Lam G, Fabrin K, et al. Reasons why not all Danish patients with muscle invasive bladder cancer receive neoadjuvant chemo-therapy before radical cystectomy. Scand J Urol. 2019;53(4):213–216.

https://doi.org/10.1080/21681805.2019.1624608 DOI: https://doi.org/10.1080/21681805.2019.1624608

Downloads

Additional Files

Published

2024-02-26

How to Cite

Körner, S. K., Dreyer, T. ., Carus, A., Dohn, L. H. ., Joensen, U. N. ., Lam, G. W. ., … Jensen, J. B. . (2024). DaBlaCa-17: nationwide observational study in Denmark on survival before and after implementation of neoadjuvant chemotherapy prior to cystectomy for muscle-invasive bladder cancer. Scandinavian Journal of Urology, 59, 39–46. https://doi.org/10.2340/sju.v59.24024

Issue

Vol. 59 (2024)

Section

Original research article

License

Copyright (c) 2024 Stefanie Korsgaard Körner, Thomas Dreyer, Andreas Carus, Line Hammer Dohn, Ulla Nordström Joensen, Gitte Wrist Lam, Niels Viggo Jensen, Knud Fabrin, Thor Knak Jensen, Helle Pappot, Mads Agerbæk, Jørgen Bjerggaard Jensen

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Acta Chirurgica Scandinavica Society owns the copyright for all material published until Volume 57 (2023) unless otherwise specified. As from Volume 59 (2024) all published articles, unless otherwise specified, are published under CC-BY licences, allowing third parties to copy and redistribute the material in any medium or format and to remix, transform, and build upon the material, with the condition of proper attribution to the original work. 

Crossref
Scopus
Google Scholar
Europe PMC

Funding data