Top

Published in:

Open Access 27-03-2023 | Original Article

Conservative treatment for high-risk NMIBC failing BCG treatment: who benefits from adding electromotive drug administration (EMDA) of mitomycin C (MMC) to a second BCG induction cycle?

Authors: Gian Maria Busetto, Marco Finati, Marco Chirico, Francesco Cinelli, Nicola D’Altilia, Ugo G. Falagario, Francesca Sanguedolce, Francesco Del Giudice, Ettore De Berardinis, Matteo Ferro, Felice Crocetto, Angelo Porreca, Luca Di Gianfrancesco, Beppe Calo’, Vito Mancini, Carlo Bettocchi, Giuseppe Carrieri, Luigi Cormio

Published in: World Journal of Urology | Issue 5/2023

Abstract

Purpose

Radical cystectomy (RC) is the standard treatment for high-risk non muscle-invasive bladder cancer (NMIBC) failing first BCG treatment. A second BCG course is an option for those patients who refuse RC or are not eligible for it, but its success rate is quite low. Aim of the present study was to determine whether the addition of intravesical electromotive drug administration of mytomicin-C (EMDA-MMC) improved the efficacy of second BCG course.

Methods

Patients with high-risk NMIBC having failed first BCG treatment and having refused RC were offered a second BCG induction course either alone (group A) or combined with EMDA-MMC (group B). Recurrence-free survival (RFS), progression-free survival (PFS) and cancer-specific survival (CSS) were tested.

Results

Of the 80 evaluable patients, 44 were in group A and 36 in group B; median follow-up was 38 months. RFS was significantly worse in group A whereas there was no difference in PFS and CSS between the two groups. Stratifying by disease stage, Ta patients receiving combined treatment had statistically better RFS and PFS survival than those receiving BCG only; this difference did not apply to T1 patients. Multivariable analysis confirmed that combined treatment was a significant predictor of recurrence and was close to predict progression. No tested variable was predictive of recurrence or progression in T1 tumours. Among those who underwent RC, CSS was 61.5% in those who had progression and 100% in those who remained with NMIBC.

Conclusion

Combined treatment improved RFS and PFS only in patients with Ta disease.

Available only for authorised users

Babjuk M, Burger M, Compérat E, Gontero P, Mostafid AH, Palou J et al (2021) Guidelines on non-muscle invasive bladder cancer 2020, Update March 2021. https://uroweb.org/guideline/non-muscle-invasive-bladder-cancer/

Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE (2016) The 2016 WHO classification of tumours of the urinary system and male genital organs-part B: prostate and bladder tumours. Eur Urol 70(1):106–119CrossRefPubMed

Paner GP, Stadler WM, Hansel DE, Montironi R, Lin DW, Amin MB (2018) Updates in the eighth edition of the tumor-node-metastasis staging classification for urologic cancers. Eur Urol 73(4):560–569CrossRefPubMed

Böhle A, Bock PR (2004) Intravesical bacille Calmette-Guérin versus mitomycin C in superficial bladder cancer: formal meta-analysis of comparative studies on tumor progression. Urology 63(4):682–686CrossRefPubMed

Oddens J, Brausi M, Sylvester R, Bono A, van de Beek C, van Andel G et al (2013) 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 63(3):462–472CrossRefPubMed

Lerner SP, Tangen CM, Sucharew H, Wood D, Crawford ED (2009) Failure to achieve a complete response to induction BCG therapy is associated with increased risk of disease worsening and death in patients with high risk non-muscle invasive bladder cancer. Urol Oncol 27(2):155–159CrossRefPubMed

Herr HW, Milan TN, Dalbagni G (2015) BCG-refractory vs BCG-relapsing non-muscle-invasive bladder cancer: a prospective cohort outcomes study. Urol Oncol 33(3):108.e1–4CrossRefPubMed

Di Stasi SM, Giannantoni A, Giurioli A, Valenti M, Zampa G, Storti L et al (2006) Sequential BCG and electromotive mitomycin versus BCG alone for high-risk superficial bladder cancer: a randomised controlled trial. Lancet Oncol 7(1):43–51CrossRefPubMed

Racioppi M, Di Gianfrancesco L, Ragonese M, Palermo G, Sacco E, Bassi PF (2018) Electro motive drug administration (EMDA) of mitomycin C as first-line salvage therapy in high risk “BCG failure” non muscle invasive bladder cancer: 3 years follow-up outcomes. BMC Cancer 18(1):1224CrossRefPubMedPubMedCentral

10.

Di Gianfrancesco L, Ragonese M, Palermo G, Sacco E, Bassi P, Racioppi M (2021) Second-line conservative device-assisted intravesical treatment in selected patients with recurrent high-risk non-muscle-invasive bladder cancer. Clin Genitourin Cancer 19(2):e100–e119CrossRefPubMed

11.

Calò B, Sanguedolce F, Falagario UG, Chirico M, Fortunato F, Carvalho-Diaz E et al (2021) Assessing treatment response after intravesical bacillus Calmette-Guerin induction cycle: are routine bladder biopsies necessary? World J Urol 39(10):3815–3821CrossRefPubMedPubMedCentral

12.

Rosevear HM, Lightfoot AJ, Birusingh KK, Maymí JL, Nepple KG, O’Donnell MA et al (2011) Factors affecting response to bacillus Calmette-Guerin plus interferon for urothelial carcinoma in situ. J Urol 186(3):817–823CrossRefPubMed

13.

Cockerill PA, Knoedler JJ, Frank I, Tarrell R, Karnes RJ (2016) Intravesical gemcitabine in combination with mitomycin C as salvage treatment in recurrent non-muscle-invasive bladder cancer. BJU Int 117(3):456–462CrossRefPubMed

14.

Barlow L, McKiernan J, Sawczuk I, Benson M (2009) A single-institution experience with induction and maintenance intravesical docetaxel in the management of non-muscle-invasive bladder cancer refractory to bacille Calmette-Guérin therapy. BJU Int 104(8):1098–1102CrossRefPubMed

15.

Steinberg G, Bahnson R, Brosman S, Middleton R, Wajsman Z, Wehle M (2000) Efficacy and safety of valrubicin for the treatment of Bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. The Valrubicin Study Group. J Urol 163(3):761–767CrossRefPubMed

16.

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):919–930CrossRefPubMed

17.

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):107–117CrossRefPubMed

18.

Tan WS, Panchal A, Buckley L, Devall AJ, Loubière LS, Am P 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):63–71CrossRefPubMed

19.

Juvet T, Mari A, Lajkosz K, Wallis C, Kuk C, Erlich A et al (2020) Sequential administration of Bacillus Calmette-Guerin (BCG) and electromotive drug administration (EMDA) of mitomycin C (MMC) for the treatment of high-grade nonmuscle invasive bladder cancer after BCG failure. Urol Oncol 38(11):8509–85015CrossRef

20.

Cormio L, Sanguedolce F, Cormio A, Massenio P, Pedicillo MC, Cagiano S et al (2017) Human epidermal growth factor receptor 2 expression is more important than Bacillus Calmette Guerin treatment in predicting the outcome of T1G3 bladder cancer. Oncotarget 8(15):25433–25441CrossRefPubMedPubMedCentral

21.

Sanguedolce F, Cormio A, Massenio P, Pedicillo MC, Cagiano S, Fortunato F et al (2018) Altered expression of HER-2 and the mismatch repair genes MLH1 and MSH2 predicts the outcome of T1 high-grade bladder cancer. J Cancer Res Clin Oncol 144(4):637–644CrossRefPubMed

22.

Crocetto F, Barone B, Ferro M, Busetto GM, La Civita E, Buonerba C et al (2022) Liquid biopsy in bladder cancer: state of the art and future perspectives. Crit Rev Oncol Hematol 170:103577CrossRefPubMed

23.

Nicolazzo C, Busetto GM, Gradilone A, Sperduti I, Del Giudice F, Loreni F et al (2019) Circulating tumor cells identify patients with super-high-risk non-muscle-invasive bladder cancer: updated outcome analysis of a prospective single-center trial. Oncologist 24(5):612–616CrossRefPubMedPubMedCentral

Title: Conservative treatment for high-risk NMIBC failing BCG treatment: who benefits from adding electromotive drug administration (EMDA) of mitomycin C (MMC) to a second BCG induction cycle?
Authors: Gian Maria Busetto
Marco Finati
Marco Chirico
Francesco Cinelli
Nicola D’Altilia
Ugo G. Falagario
Francesca Sanguedolce
Francesco Del Giudice
Ettore De Berardinis
Matteo Ferro
Felice Crocetto
Angelo Porreca
Luca Di Gianfrancesco
Beppe Calo’
Vito Mancini
Carlo Bettocchi
Giuseppe Carrieri
Luigi Cormio
Publication date: 27-03-2023
Publisher: Springer Berlin Heidelberg
Published in: World Journal of Urology / Issue 5/2023
Print ISSN: 0724-4983
Electronic ISSN: 1433-8726
DOI: https://doi.org/10.1007/s00345-023-04372-5

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Conservative treatment for high-risk NMIBC failing BCG treatment: who benefits from adding electromotive drug administration (EMDA) of mitomycin C (MMC) to a second BCG induction cycle?

Abstract

Purpose

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 5/2023

Comparison between ketorolac- and fentanyl-based patient-controlled analgesia for acute kidney injury after robot-assisted radical prostatectomy: a retrospective propensity score-matched analysis

Case-based review of dietary management of cystinuria

Patient compliance to dietary recommendations: tips and tricks to improve compliance rates

German specialists treating testicular cancer follow different guidelines with resulting inconsistency in assessment of retroperitoneal lymph-node metastasis: clinical implications and possible corrective measures

Pelvic radiation-induced urinary strictures: etiology and management of a challenging disease

Preoperative fibrinogen/CRP score predicts survival in upper urothelial tract carcinoma patients undergoing radical curative surgery