Skip to main content

Advertisement

SpringerLink
Log in

Efficacy of hyperthermic intravesical chemotherapy (HIVEC) in patients with non-muscle invasive bladder cancer after BCG failure

  • Topic Paper
  • Published:
World Journal of Urology Aims and scope Submit manuscript

Abstract

Purpose

To evaluate hyperthermic intravesical chemotherapy (HIVEC) efficacy regarding 1-year disease-free survival (RFS) rate and bladder preservation rate in patients with non-muscle invasive bladder cancer (NMIBC) who fail bacillus Calmette–Guérin (BCG) therapy.

Methods

This is a multicenter retrospective series from a national database (7 expert centers). Between January 2016 and October 2021, patients treated with HIVEC for NMIBC who failed BCG have been included in our study. These patients had a theoretical indication for cystectomy but were ineligible for surgery or refused it.

Results

A total of 116 patients treated with HIVEC and with a follow-up > 6 months were included in this study and retrospectively analyzed. The median follow-up was 20.6 months. The 12 month-RFS (recurrence-free survival) rate was 62.9%. The bladder preservation rate was 87.1%. Fifteen patients (12.9%) progressed to muscle infiltration, three of them having a metastatic disease at the time of progression. Predictive factors of progression were T1 stage, high grade and very high-risk tumors according to the EORTC classification.

Conclusion

Chemohyperthermia using HIVEC achieved an RFS rate of 62.9% at 1 year and enabled a bladder preservation rate of 87.1%. However, the risk of progression to muscle-invasive disease is not negligible, particularly for patients with very high-risk tumors. In these patients who fail BCG, cystectomy should remain the standard of care and HIVEC may be discussed cautiously for patients who are not eligible for surgery and well informed of the risk of progression.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

Data availability

We ensure that all related data are available to the organization, partners, or users at any time, whenever and wherever required.

References

  1. Witjes JA (2006) Management of BCG failures in superficial bladder cancer: a review. Eur Urol 49(5):790–797. https://doi.org/10.1016/j.eururo.2006.01.017

    Article  PubMed  Google Scholar 

  2. Babjuk M, Burger M, Capoun O, Cohen D, Compérat EM, Dominguez Escrig JL et al (2022) European association of urology guidelines on non-muscle-invasive bladder cancer (TaT1 and Carcinoma In Situ). Eur Urol 81(1):75–94. https://doi.org/10.1016/j.eururo.2021.08.010

    Article  PubMed  Google Scholar 

  3. van der Heijden AG, Verhaegh G, Jansen CFJ, Schalken JA, Witjes JA (2015) Effect of hyperthermia on the cytotoxicity of 4 chemotherapeutic agents currently used for the treatment of transitional cell carcinoma of the bladder: an in vitro study. J Urol 173(4):1375–1380. https://doi.org/10.1097/01.ju.0000146274.85012.e1

    Article  Google Scholar 

  4. Arends TJH, Nativ O, Maffezzini M, de Cobelli O, Canepa G, Verweij F et al (2016) Results of a randomised controlled trial comparing intravesical chemohyperthermia with mitomycin C versus bacillus Calmette-Guérin for adjuvant treatment of patients with intermediate- and high-risk non–muscle-invasive bladder cancer. Eur Urol 69(6):1046–1052. https://doi.org/10.1016/j.eururo.2016.01.006

    Article  CAS  PubMed  Google Scholar 

  5. Tan WS, Panchal A, Buckley L, Devall AJ, Loubière LS, Pope AM et al (2019) Radiofrequency-induced thermo-chemotherapy effect versus a second course of Bacillus Calmette-Guérin or institutional standard in patients with recurrence of non-muscle-invasive bladder cancer following induction or maintenance Bacillus Calmette-Guérin therapy (HYMN): a phase III, open-label. Randomised Controlled Trial Eur Urol 75(1):63–71. https://doi.org/10.1016/j.eururo.2018.09.005

    Article  PubMed  Google Scholar 

  6. Sousa A, Piñeiro I, Rodríguez S, Aparici V, Monserrat V, Neira P et al (2016) Recirculant hyperthermic IntraVEsical chemotherapy (HIVEC) in intermediate–high-risk non-muscle-invasive bladder cancer. Int J Hyperthermia 32(4):374–380. https://doi.org/10.3109/02656736.2016.1142618

    Article  CAS  PubMed  Google Scholar 

  7. de Jong JJ, Hendricksen K, Rosier M, Mostafid H, Boormans JL (2018) Hyperthermic intravesical chemotherapy for BCG unresponsive non-muscle invasive bladder cancer patients. Bladder Cancer 4(4):395–401. https://doi.org/10.3233/blc-180191

    Article  PubMed  PubMed Central  Google Scholar 

  8. Tan WS, Prendergast A, Ackerman C, Yogeswaran Y, Cresswell J, Mariappan P et al (2022) Adjuvant intravesical chemohyperthermia versus passive chemotherapy in patients with intermediate-risk non-muscle-invasive bladder cancer (HIVEC-II): a phase 2, open-label. Randomised Controlled Trial Eur Urol S0302–2838(22):02552. https://doi.org/10.1016/j.eururo.2022.08.003

    Article  CAS  Google Scholar 

  9. Kamat AM, Sylvester RJ, Böhle A, Palou J, Lamm DL, Brausi M et al (2016) Definitions, end points, and clinical trial designs for non–muscle-invasive bladder cancer: recommendations from the international bladder cancer group. J Clin Oncol 34(16):1935–1944. https://doi.org/10.1200/jco.2015.64.4070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Irani J (2016) Intravesical instillations in non-muscle-invasive bladder cancer (NMIBC). Prospects for thermochemotherapy. Prog Urol 6(14):860–864. https://doi.org/10.1016/j.purol.2016.09.057

    Article  Google Scholar 

  11. Nouhaud FX, Chakroun M, Lenormand C, Ouzaid I, Peyronnet B, Gryn A et al (2021) Comparison of the prognosis of primary vs. progressive muscle invasive bladder cancer after radical cystectomy: results from a large multicenter study. Urol Oncol 39(3):195.e1-195.e6. https://doi.org/10.1016/j.urolonc.2020.09.006

    Article  PubMed  Google Scholar 

  12. Balar AV, Kamat AM, Kulkarni GS, Uchio EM, Boormans JL, Roumiguié M et al (2021) Pembrolizumab monotherapy for the treatment of high-risk non-muscle-invasive bladder cancer unresponsive to BCG (KEYNOTE-057): an open-label, single-arm, multicentre, phase 2 study. Lancet Oncol 22(7):919–930. https://doi.org/10.1016/S1470-2045(21)00147-9

    Article  CAS  PubMed  Google Scholar 

  13. García-Perdomo HA, Sánchez AL, Spiess PE (2022) Immune checkpoints inhibitors in the management of high-risk non-muscle-invasive bladder cancer. A scoping review. Urol Oncol 40(9):409.e1-409.e8. https://doi.org/10.1016/j.urolonc.2022.02.003

    Article  CAS  PubMed  Google Scholar 

  14. Boorjian SA, Alemozaffar M, Konety BR, Shore ND, Gomella LG, Kamat AM et al (2021) Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol 22(1):107–117. https://doi.org/10.1016/S1470-2045(20)30540-4

    Article  CAS  PubMed  Google Scholar 

  15. Packiam VT, Richards J, Schmautz M, Heidenreich A, Boorjian SA (2021) The current landscape of salvage therapies for patients with bacillus Calmette-Guérin unresponsive nonmuscle invasive bladder cancer. Curr Opin Urol 31(3):178–187. https://doi.org/10.1097/MOU.0000000000000863

    Article  PubMed  Google Scholar 

  16. Foltz JA, Hess BT, Bachanova V, Bartlett NL, Berrien-Elliott MM, McClain E et al (2021) Phase I trial of N-803, an Il15 receptor agonist, with rituximab in patients with indolent non-hodgkin lymphoma. Clin Cancer Res 27(12):3339–3350. https://doi.org/10.1158/1078-0432.CCR-20-4575

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kamat AM, Lerner SP, O’Donnell M, Georgieva MV, Yang M, Inman BA et al (2020) Evidence-based assessment of current and emerging bladder-sparing therapies for non–muscle-invasive bladder cancer after Bacillus Calmette-Guerin therapy: a systematic review and meta-analysis. Eur Urol Oncol 3(3):318–340. https://doi.org/10.1016/j.euo.2020.02.006

    Article  PubMed  Google Scholar 

  18. Friedrich MG, Pichlmeier U, Schwaibold H, Conrad S, Huland H (2007) Long-term intravesical adjuvant chemotherapy further reduces recurrence rate compared with short-term intravesical chemotherapy and short-term therapy with Bacillus Calmette-Guérin (BCG) in patients with non-muscle-invasive bladder carcinoma. Eur Urol 52(4):1123–1129. https://doi.org/10.1016/j.eururo.2007.02.063

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgical Oncology 2, Institut Paoli Calmettes Cancer Center, 232 Boulevard de Ste Marguerite, 13009, Marseille, France

    Géraldine Pignot, Laure Doisy & Jochen Walz

  2. Department of Urology and Kidney Transplantation, Aix-Marseille University, APHM, Conception Academic Hospital, Marseille, France

    Michael Baboudjian & Eric Lechevallier

  3. Department of Urology, Kremlin-Bicêtre Academic Hospital, Bicêtre, France

    Cédric Lebacle & Jacques Irani

  4. Department of Urology, Université de Paris, APHP, Saint Louis Hospital, Paris, France

    Alexandre Chamouni & Alexandra Masson-Lecomte

  5. Department of Urology, Centre Hospitalier Universitaire Caen, Caen, France

    Xavier Tillou & Thibaut Waeckel

  6. Department of Urology, Polyclinique du Parc Rambot, Hôpital Privé de Provence, Aix-en-Provence, France

    Arnaud Monges

  7. Department of Medical Oncology, Institut Paoli Calmettes Cancer Center, Marseille, France

    Gwenaelle Gravis

  8. Department of Urology, University Hospital François Mitterrand, Dijon, France

    Eric Mourey & Céline Duperron

Authors
  1. Géraldine Pignot
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael Baboudjian
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cédric Lebacle
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alexandre Chamouni
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Eric Lechevallier
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jacques Irani
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xavier Tillou
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Thibaut Waeckel
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Arnaud Monges
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Laure Doisy
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Jochen Walz
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Gwenaelle Gravis
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Eric Mourey
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Céline Duperron
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Alexandra Masson-Lecomte
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

GP: project development, data collection, data management, data analysis, manuscript writing. MB: data collection, data management, data analysis. CL: Data collection. AC: data collection. EL: project development, manuscript editing. JI: project development, data analysis, manuscript editing. XT: manuscript editing. TW: data collection. AM: data collection LD: data collection, data management, data analysis. JW: manuscript editing. GG: manuscript editing. EM: data collection. CD: data collection, manuscript editing. AM-L: data collection, manuscript editing.

Corresponding author

Correspondence to Géraldine Pignot.

Ethics declarations

Conflict of interest

The authors have no conflicts of interest related to the subject of this manuscript.

Ethical approval

The study design was approved by the appropriate ethics review board (approved protocol number: THERMO-MMC-IPC 2019–019).

Research involving human participants and/or animals

Retrospective collection of data—Study submitted and approved by the ethics committee of Institut Paoli-Calmettes (THERMO-MMC).

Informed consent

N/A.

Additional information

Publisher's Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Pignot, G., Baboudjian, M., Lebacle, C. et al. Efficacy of hyperthermic intravesical chemotherapy (HIVEC) in patients with non-muscle invasive bladder cancer after BCG failure. World J Urol 41, 3195–3203 (2023). https://doi.org/10.1007/s00345-023-04332-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00345-023-04332-z

Keywords

Search

Navigation