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Comparison of hyperthermic intravesical chemotherapy and Bacillus Calmette–Guerin therapy in high-risk non-muscle invasive bladder cancer: a matched-pair analysis

  • Urology - Original Paper
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Abstract

Purpose

To compare adjuvant hyperthermic intravesical chemotherapy (HIVEC) with mitomycin C and standard Bacillus Calmette–Guerin (BCG) therapy in terms of oncological outcomes and adverse events in patients with high-risk non-muscle-invasive bladder cancer (NMIBC).

Materials and methods

The data of patients with high-risk papillary NMIBC treated with adjuvant intravesical BCG instillations or HIVEC in our institution between June 2017 and August 2022 were analyzed retrospectively. Twenty-four patients who received HIVEC were matched 1:1 with patients receiving BCG therapy based on tumor characteristics (tumor stage and grade), age, gender, smoking status, and the number of tumors (single or multiple). HIVEC and standard BCG treatments were compared in terms of recurrence-free survival (RFS), progression-free survival (PFS), and adverse events.

Results

Forty-eight patients (24 in the BCG group and 24 in the HIVEC group) were included in the study. The median follow-up times of the BCG and HIVEC groups were 32 [interquartile range (IQR): 28.0–47.8] and 28 (IQR: 16.7–41.8) months, respectively (p = 0.11). There was no significant difference between the groups in terms of the 24-month RFS (BCG 83% vs HIVEC 88%, p = 0.64) and the 24-month PFS (BCG 100% vs HIVEC 94%, p = 0.61). Regarding the safety profile, at least one adverse event occurred in 13 (54%) of the patients in the BCG group and 12 (50.0%) of those in the HIVEC group (p = 0.77).

Conclusion

This study demonstrated that HIVEC with mitomycin C has a similar oncological efficacy and safety profile to standard BCG therapy in high-risk NMIBC.

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References

  1. Bray F et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68(6):394–424

    Article  PubMed  Google Scholar 

  2. Veeratterapillay R et al (2016) High-risk non-muscle-invasive bladder cancer-therapy options during intravesical BCG shortage. Curr Urol Rep 17(9):68

    Article  PubMed  PubMed Central  Google Scholar 

  3. Kamat AM et al (2016) Bladder cancer. Lancet 388(10061):2796–2810

    Article  PubMed  Google Scholar 

  4. Babjuk M et al (2022) European association of urology guidelines on non-muscle-invasive bladder cancer (Ta, T1, and carcinoma in situ). Eur Urol 81(1):75–94

    Article  PubMed  Google Scholar 

  5. Sousa A et al (2014) A clinical trial of neoadjuvant hyperthermic intravesical chemotherapy (HIVEC) for treating intermediate and high-risk non-muscle invasive bladder cancer. Int J Hyperthermia 30(3):166–170

    Article  CAS  PubMed  Google Scholar 

  6. Field SB, Bleehen NM (1979) Hyperthermia in the treatment of cancer. Cancer Treat Rev 6(2):63–94

    Article  CAS  PubMed  Google Scholar 

  7. Fajardo LF et al (1988) Hyperthermia inhibits angiogenesis. Radiat Res 114(2):297–306

    Article  ADS  CAS  PubMed  Google Scholar 

  8. Tan WP et al (2020) Safety and efficacy of intravesical chemotherapy and hyperthermia in the bladder: results of a porcine study. Int J Hyperthermia 37(1):854–860

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Shariat SF et al (2010) Update on intravesical agents for non-muscle-invasive bladder cancer. Immunotherapy 2(3):381–392

    Article  CAS  PubMed  Google Scholar 

  10. Lammers RJ et al (2011) The role of a combined regimen with intravesical chemotherapy and hyperthermia in the management of non-muscle-invasive bladder cancer: a systematic review. Eur Urol 60(1):81–93

    Article  MathSciNet  PubMed  Google Scholar 

  11. Arrabal Polo MA et al (2023) Adjuvant intravesical treatment in patients with intermediate and high-risk non-muscle-invasive bladder cancer with BCG versus MMC applied with COMBAT or EMDA results of a prospective study. J Cancer Res Clin Oncol 149(10):7453–7459

    Article  CAS  PubMed  Google Scholar 

  12. Guerrero-Ramos F et al (2022) Recirculating hyperthermic intravesical chemotherapy with mitomycin C (HIVEC) versus BCG in high-risk non-muscle-invasive bladder cancer: results of the HIVEC-HR randomized clinical trial. World J Urol 40(4):999–1004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Ekin RG et al (2015) Intravesical bacillus Calmette-Guerin versus chemohyperthermia for high-risk non-muscle-invasive bladder cancer. Can Urol Assoc J 9(5–6):E278–E283

    Article  PubMed  PubMed Central  Google Scholar 

  14. Thyavihally YB et al (2021) Comparing adverse effects, short term outcomes, and cost implications of hyperthermic intravesical chemotherapy with Mitomycin-C and intravesical bacillus Calmette-Guerin instillation (Moscow-I strain) in the management of intermediate and high-risk nonmuscle invasive bladder cancer. Urol Ann 13(4):424–430

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chiancone F, Carrino M, Fedelini M et al (2019) Intravesical thermo-chemotherapy using the combined antineoplastic thermotherapy bladder recirculation system for BCG-failure patients: a single center experience. Eur Urol Suppl 18:e3248

    Article  Google Scholar 

  16. Sood R et al (2020) A prospective comparative study to assess the efficacy and tolerability of 2 different doses of intravesical bacillus Calmette-Guerin (BCG) in patients with non-muscle-invasive bladder cancer. Urol Oncol 38(5):433–439

    Article  CAS  PubMed  Google Scholar 

  17. NCI. National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0. 2017. Accessed 14 sep 2020. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm

  18. Chua TC et al (2009) Intraoperative hyperthermic intraperitoneal chemotherapy after cytoreductive surgery in ovarian cancer peritoneal carcinomatosis: systematic review of current results. J Cancer Res Clin Oncol 135(12):1637–1645

    Article  PubMed  Google Scholar 

  19. Gill RS et al (2011) Treatment of gastric cancer with peritoneal carcinomatosis by cytoreductive surgery and HIPEC: a systematic review of survival, mortality, and morbidity. J Surg Oncol 104(6):692–698

    Article  PubMed  Google Scholar 

  20. Verwaal VJ et al (2003) Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer. J Clin Oncol 21(20):3737–3743

    Article  PubMed  Google Scholar 

  21. Liu K et al (2020) Thermal intravesical chemotherapy reduce recurrence rate for non-muscle invasive bladder cancer patients: a meta-analysis. Front Oncol 10:29

    Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

  22. Angulo JC et al (2023) Hyperthermic mitomycin C in intermediate-risk non-muscle-invasive bladder cancer: results of the HIVEC-1 trial. Eur Urol Oncol 6(1):58–66

    Article  PubMed  Google Scholar 

  23. Tan WS 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 83(6):497–504

    Article  PubMed  Google Scholar 

  24. de Jong JJ et al (2018) Hyperthermic intravesical chemotherapy for BCG unresponsive non-muscle invasive bladder cancer patients. Bladder Cancer 4(4):395–401

    Article  PubMed  PubMed Central  Google Scholar 

  25. Pijpers OM et al (2022) Long-term efficacy of hyperthermic intravesical chemotherapy for BCG-unresponsive non-muscle invasive bladder cancer. Urol Oncol 40(2):62-e13-62-e20

    Article  PubMed  Google Scholar 

  26. Doisy L et al (2021) Efficacy of HIVEC in patients with high-risk non-muscle invasive bladder cancer who are contraindicated to BCG and in patients who fail BCG therapy. Int J Hyperthermia 38(1):1633–1638

    Article  CAS  PubMed  Google Scholar 

  27. Di Stasi SM et al (2003) Intravesical electromotive mitomycin C versus passive transport mitomycin C for high risk superficial bladder cancer: a prospective randomized study. J Urol 170(3):777–782

    Article  MathSciNet  PubMed  Google Scholar 

  28. Arends TJ et al (2016) Results of a randomised controlled trial comparing intravesical chemohyperthermia with mitomycin C versus bacillus Calmette-Guerin for adjuvant treatment of patients with intermediate- and high-risk non-muscle-invasive bladder cancer. Eur Urol 69(6):1046–1052

    Article  CAS  PubMed  Google Scholar 

  29. Zhao H et al (2021) Intravesical chemohyperthermia vs. bacillus Calmette-Guerin instillation for intermediate- and high-risk non-muscle invasive bladder cancer: a systematic review and meta-analysis. Front Surg 8:775527

    Article  PubMed  PubMed Central  Google Scholar 

  30. Zeng N et al (2023) Hyperthermia intravesical chemotherapy acts as a promising alternative to bacillus Calmette-Guerin instillation in non-muscle-invasive bladder cancer: a network meta-analysis. Front Oncol 13:1164932

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. You C et al (2023) Device-assisted intravesical chemotherapy versus bacillus Calmette-Guerin for intermediate or high-risk non-muscle invasive bladder cancer: a systematic reviewer and meta-analysis. Int Urol Nephrol. https://doi.org/10.1007/s11255-023-03765-0

    Article  PubMed  Google Scholar 

  32. Ojea A et al (2007) A multicentre, randomised prospective trial comparing three intravesical adjuvant therapies for intermediate-risk superficial bladder cancer: low-dose bacillus Calmette-Guerin (27 mg) versus very low-dose bacillus Calmette-Guerin (135 mg) versus mitomycin C. Eur Urol 52(5):1398–1406

    Article  CAS  PubMed  Google Scholar 

  33. Michielsen D et al (2005) Mitomycin C and epirubicin: functional bladder damage in rats after repeat intravesical instillations. J Urol 173(6):2166–2170

    Article  CAS  PubMed  Google Scholar 

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Funding

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Authors and Affiliations

  1. Department of Urology, Haseki Training and Research Hospital, Istanbul, Turkey

    Yasar Pazir, Abdullah Esmeray, Ufuk Caglar, Akif Erbin, Faruk Ozgor, Omer Sarilar & Fatih Akbulut

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  1. Yasar Pazir
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  2. Abdullah Esmeray
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  3. Ufuk Caglar
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  4. Akif Erbin
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  5. Faruk Ozgor
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Contributions

All authors read and approved the final manuscript. YP: project development, data collection + analysis, manuscript writing/editing. AE, AE: data collection + analysis, manuscript writing. UC, OS, FO: manuscript writing/editing + data analysis. MFA: project development, data collection + analysis, manuscript writing/editing.

Corresponding author

Correspondence to Yasar Pazir.

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Conflicts of interest

All authors have no conflict of interest.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Haseki Training and Research Hospital (2022-214).

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Informed consent was obtained from all patients included in the study.

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Pazir, Y., Esmeray, A., Caglar, U. et al. Comparison of hyperthermic intravesical chemotherapy and Bacillus Calmette–Guerin therapy in high-risk non-muscle invasive bladder cancer: a matched-pair analysis. Int Urol Nephrol 56, 957–963 (2024). https://doi.org/10.1007/s11255-023-03849-x

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