AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025080033
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ORIGINAL RESEARCH ARTICLE

Thermochemotherapy with epirubicin for recurrent non-muscle invasive bladder cancers: A pilot study using the UniThermia system

Sever Chiujdea1,2,3 ,  Octavian Sabin Tataru2 ,  Martha Orsolya1,3 ,  Beat Roth4 ,  Daniel Porav-Hodade1,3 ,  Matteo Ferro5 ,  Mihai Dorin Vartolomei4,6*
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1 Department of Urology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, Transylvania, Romania
2 Doctoral School of Medicine and Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Targu Mures, Transylvania, Romania
3 Department of Clinic Urology, County Hospital of Targu Mures, Targu Mures, Transylvania, Romania
4 Department of Urology, Faculty of Medicine, University of Bern, Bern, Switzerland
5 Department of Health Science, Faculty of Medicine, University Study of Milan, ASST Santi Paolo and Carlo, Milan, Italy
6 The Organizing Institution for Doctoral Studies (IOSUD), Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
EJMO, 025080033 https://doi.org/10.36922/EJMO025080033
Received: 18 February 2025 | Revised: 24 March 2025 | Accepted: 18 April 2025 | Published online: 6 May 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Bladder cancer (BC) ranks as the 10th most common cancer globally, predominantly affecting older adults. Non-muscle invasive BC (NMIBC) are known for high recurrence and progression rates despite standard treatments. This study assesses the efficacy of chemohyperthermia with epirubicin in Bacillus Calmette–Guérin (BCG)-naïve patients with either primary or recurrent NMIBC. We conducted a prospective pilot study on this cohort using the bladder wall thermochemotherapy – UniThermia platform, with a follow-up period of 24 months. Nine NMIBC patients (88.89% male; mean age: 70.22 ± 11.82 years) were prospectively enrolled. Inclusion criteria were NMIBC stage Ta–T1 with BCG-naïve status; patients with carcinoma in situ (CIS) were excluded. Tumor staging revealed pTa in six patients and pT1 in three patients; tumor grading included G1 (11.11%) and G2 (88.89%). No CIS was detected. All patients received six weekly chemohyperthermia instillations. At the 24-month follow-up, four patients (44.4%) achieved a complete response with no recurrences; all remained alive with no disease progression. All recurrences were low-grade pTa. These findings suggest that chemohyperthermia with epirubicin may offer therapeutic advantages over intravesical BCG or conventional chemotherapy, especially for BCG-intolerant or refractory patients. Study limitations include the small sample size and limited follow-up duration. Further multicenter studies are warranted to validate these preliminary results. Overall, chemohyperthermia with epirubicin appears to be a promising alternative for the management of recurrent NMIBC when standard BCG treatment is ineffective or unavailable.

Keywords
Chemohyperthermia
Epirubicin
Intermediate-risk bladder cancer
Non-muscle invasive bladder cancer
Funding
A postdoctoral grant awarded to Assoc. Prof. Dr. Mihai Dorin Vartolomei by The Executive Unit for Financing Higher Education, Research, Development, and Innovation (UEFISCDI): [PN-III-P1-1.1-PD-2019-0085] for this study.
Conflict of interest
Mihai Dorin Vartolomei is an Editorial Board Member of this journal but was not involved in the editorial or peer-review process for this paper, either directly or indirectly. Separately, all other authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
References
  1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249. doi: 10.3322/caac.21660

 

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA Cancer J Clin. 2017;67(1):7-30. doi: 10.3322/caac.21387

 

  1. Babjuk M, Böhle A, Burger M, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: Update 2016. Eur Urol. 2017;71(3):447-461. doi: 10.1016/j.eururo.2016.05.041

 

  1. Cookson MS, Chang SS, Oefelein MG, Gallagher JR, Schwartz B, Heap K. National practice patterns for immediate postoperative instillation of chemotherapy in nonmuscle invasive bladder cancer. J Urol. 2012;187(5):1571-1576. doi: 10.1016/j.juro.2011.12.056

 

  1. Kassouf W, Traboulsi SL, Kulkarni GS, et al. CUA guidelines on the management of non-muscle invasive bladder cancer. Can Urol Assoc J. 2015;9(9-10):E690-E704. doi: 10.5489/cuaj.3320

 

  1. Chang SS, Boorjian SA, Chou R, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/ SUO guideline. J Urol. 2016;196(4):1021-1029. doi: 10.1016/j.juro.2016.06.049

 

  1. Yamamoto S, Kageyama Y, Fujii Y, Aizawa T, Urakami S, Fukui I. Randomized study of postoperative single intravesical instillation with pirarubicin and mitomycin c for low-risk bladder cancer. Anticancer Res. 2020;40(9):5295-5299. doi: 10.21873/anticanres.14535

 

  1. Daryanto B, Purnomo AF, Seputra KP, Budaya TN. Comparison between intravesical chemotherapy epirubicin and mitomycin-C after TURB vs TURB alone with recurrence rate of non-muscle invasive bladder cancer: Meta-analysis. Med Arch. 2022;76(3):198-201. doi: 10.5455/medarh.2022.76.198-201

 

  1. Gurram S, Rathi N. Device-assisted therapy in non-muscle-invasive bladder cancer. Bladder Cancer. 2024;10(3):167-182. doi: 10.3233/BLC-240032

 

  1. Chiujdea S, Ferro M, Vartolomei MD, et al. Epirubicin and non-muscle invasive bladder cancer treatment: A systematic review. J Clin Med. 2024;13(13):3789. doi: 10.3390/jcm13133789

 

  1. Treatments - BWT - UniThermia. Elmedical Ltd. Available from: https://www.elmedical/group.com/treatments/treatments- BWT-unithermia [Last accessed on 2024 Dec 26].

 

  1. Melekos MD, Zarakovitis IE, Fokaefs ED, et al. Intravesical Bacillus Calmette-Guérin versus epirubicin in the prophylaxis of recurrent and/or multiple superficial bladder tumours. Oncology. 1996;53(4):281-288. doi: 10.1159/000227574

 

  1. Tozawa K, Okamura T, Sasaki S, et al. Intravesical combined chemoimmunotherapy with epirubicin and Bacillus Calmette-Guérin is not indicated for superficial bladder cancer. Urol Int. 2001;67(4):289-292. doi: 10.1159/000051005

 

  1. Cheng CW, Chan SFP, Chan LW, et al. 15-year experience on intravesical therapy of T1G3 urinary bladder cancer: A conservative approach. Jpn J Clin Oncol. 2004;34(4):202-205. doi: 10.1093/jjco/hyh030

 

  1. Cheng CW, Chan SFP, Chan LW, et al. Twelve-year follow up of a randomized prospective trial comparing bacillus Calmette-Guerin and epirubicin as adjuvant therapy in superficial bladder cancer. Int J Urol. 2005;12(5):449-455. doi: 10.1111/j.1442-2042.2005.01064.x

 

  1. Iida S, Kondo T, Kobayashi H, Hashimoto Y, Goya N, Tanabe K. Clinical outcome of high-grade non-muscle-invasive bladder cancer: A long-term single center experience. Int J Urol. 2009;16(3):287-292. doi: 10.1111/j.1442-2042.2008.02239.x

 

  1. Duchek M, Johansson R, Jahnson S, et al. Bacillus Calmette- Guérin is superior to a combination of epirubicin and interferon-alpha2b in the intravesical treatment of patients with stage T1 urinary bladder cancer. A prospective, randomized, Nordic study. Eur Urol. 2010;57(1):25-31. doi: 10.1016/j.eururo.2009.09.038

 

  1. Marttila T, Järvinen R, Liukkonen T, et al. Intravesical Bacillus Calmette-Guérin versus combination of epirubicin and interferon-α2a in reducing recurrence of non-muscle-invasive bladder carcinoma: Finnbladder-6 study. Eur Urol. 2016;70(2):341-347. doi: 10.1016/j.eururo.2016.03.034

 

  1. Blanc J, Ruggiero J, Lucca I, Arnold N, Kiss B, Roth B. Hyperthermic intravesical chemotherapy (HIVEC) using epirubicin in an optimized setting in patients with NMIBC recurrence after failed BCG therapy. Cancers (Basel). 2024;16(7):1398. doi: 10.3390/cancers16071398

 

  1. Oddens J, Brausi M, Sylvester R, et al. Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guérin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: One-third dose versus full dose and 1 year versus 3 years of maintenance. Eur Urol. 2013;63(3):462-472. doi: 10.1016/j.eururo.2012.10.039

 

  1. Milla P, Fiorito C, Soria F, Arpicco S, Cattel L, Gontero P. Intravesical thermo-chemotherapy based on conductive heat: A first pharmacokinetic study with mitomycin C in superficial transitional cell carcinoma patients. Cancer Chemother Pharmacol. 2014;73(3):503-509. doi: 10.1007/s00280-014-2381-4

 

  1. Soria F, Milla P, Fiorito C, et al. Efficacy and safety of a new device for intravesical thermochemotherapy in non-grade 3 BCG recurrent NMIBC: A phase I-II study. World J Urol. 2016;34(2):189-195. doi: 10.1007/s00345-015-1595-3

 

  1. Gözen AS, Umari P, Scheitlin W, Su FE, Akin Y, Rassweiler J. Effectivity of intravescical thermo-chemotherapy prophylaxis for patients with high recurrence and progression risk for non-muscle invasive bladder cancer. Arch Ital Urol Androl. 2017;89(2):102-105. doi: 10.4081/aiua.2017.2.102

 

  1. Ekin RG, Akarken I, Zorlu F, et al. Intravesical Bacillus Calmette-Guérin versus chemohyperthermia for high-risk non-muscle-invasive bladder cancer. Can Urol Assoc J. 2015;9(5-6):E278-E283. doi: 10.5489/cuaj.2708

 

  1. Hemdan T, Johansson R, Jahnson S, et al. 5-year outcome of a randomized prospective study comparing Bacillus Calmette- Guérin with epirubicin and interferon-α2b in patients with T1 bladder cancer. J Urol. 2014;191(5):1244-1249. doi: 10.1016/j.juro.2013.11.005

 

  1. Chiancone F, Fabiano M, Fedelini M, Meccariello C, Carrino M, Fedelini P. Outcomes and complications of hyperthermic intravesical chemotherapy using mitomycin C or epirubicin for patients with non-muscle invasive bladder cancer after bacillus Calmette-Guérin treatment failure. Cent European J Urol. 2020;73(3):287-294. doi: 10.5173/ceju.2020.0148

 

  1. Eto H, Oka Y, Ueno K, et al. Comparison of the prophylactic usefulness of epirubicin and doxorubicin in the treatment of superficial bladder cancer by intravesical instillation: A multicenter randomized trial. Kobe university urological oncology group. Cancer Chemother Pharmacol. 1994;35 Supp1:S46-S51. doi: 10.1007/BF00686919

 

  1. Ryoji O, Toma H, Nakazawa H, et al. A phase II study of prophylactic intravesical chemotherapy with epirubicin in the treatment of superficial bladder cancer. Tokyo women’s medical college bladder cancer collaborating group. Cancer Chemother Pharmacol. 1994;35(S1):S60-S64. doi: 10.1007/BF00686922

 

  1. Watanabe N, Miyagawa I, Higasibori Y, et al. Phase II study of intravesical chemoprophylaxis of epirubicin after transurethral resection of bladder tumors. Tottori university oncology group. Cancer Chemother Pharmacol. 1994;35(S1):S57-S59. doi: 10.1007/BF00686921

 

  1. Ali-El-Dein B, Barakat TS, Nabeeh A, Ibrahiem EHI. Weekly intravesical Bacillus Calmette-Guerin (BCG) alternating with epirubicin in Ta and T1 urothelial bladder cancer: An approach to decrease BCG toxicity. Urol Ann. 2013;5(2):103-108. doi: 10.4103/0974-7796.110008

 

  1. Okamura K, Kinukawa T, Tsumura Y, et al. A randomized study of short-versus long-term intravesical epirubicin instillation for superficial bladder cancer. Nagoya university urological oncology group. Eur Urol. 1998;33(3):285-288; discussion 289. doi: 10.1159/000019581

 

  1. Torelli F, Catanzaro F, Conti G, et al. High-dose epirubicin in the prophylactic treatment of T1G2 superficial bladder tumors. Eur Urol. 2001;39(Suppl 2):11-14. doi: 10.1159/000052551

 

  1. Bassi P, Spinadin R, Longo F, et al. Delayed high-dose intravesical epirubicin therapy of superficial bladder cancer. A way to reduce the side effects and increase the efficacy--a phase 2 trial. Urol Int. 2002;68(4):216-219. doi: 10.1159/000058438

 

  1. Mitsumori K, Tsuchiya N, Habuchi T, et al. Early and large-dose intravesical instillation of epirubicin to prevent superficial bladder carcinoma recurrence after transurethral resection. BJU Int. 2004;94(3):317-321. doi: 10.1111/j.1464-410X.2004.04884.x

 

  1. Ferro M, Chiujdea S, Musi G, et al. Impact of age on outcomes of patients with pure carcinoma in situ of the bladder: Multi-institutional cohort analysis. Clin Genitourin Cancer. 2022;20(2):e166-e172. doi: 10.1016/j.clgc.2021.12.005

 

  1. Dr. Soon-Shiong Highlights Data on N-803 in NMIBC. Urology Times; 2024. Available from: https://www. urologytimes.com/view/dr/soon/shiong/highlights/data/ on/n/803/in/nmibc [Last accessed on 2024 Jul 18].

 

  1. Khadhouri S, Hramyka A, Gallagher K, et al. Machine learning and external validation of the identify risk calculator for patients with haematuria referred to secondary care for suspected urinary tract cancer. Eur Urol Focus. 2024;10:1034-1042. doi: 10.1016/j.euf.2024.06.004

 

  1. Prata F, Anceschi U, Taffon C, et al. Real-time urethral and ureteral assessment during radical cystectomy using ex-vivo optical imaging: A novel technique for the evaluation of fresh unfixed surgical margins. Curr Oncol. 2023;30(3):3421-3431. doi: 10.3390/curroncol30030259

 

  1. Matuszczak M, Salagierski M. Diagnostic and prognostic potential of biomarkers CYFRA 21.1, ERCC1, p53, FGFR3 and TATI in bladder cancers. Int J Mol Sci. 2020;21(9):3360. doi: 10.3390/ijms21093360
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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