The Role of Mitomycin C in Intermediate-risk Non-muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis

Pietro Scilipoti; Aleksander Ślusarczyk; Mario de Angelis; Francesco Soria; Benjamin Pradere; Wojciech Krajewski; David D'Andrea; Andrea Mari; Francesco Del Giudice; Renate Pichler; José Daniel Subiela; Luca Afferi; Simone Albisinni; Laura Mertens; Ekaterina Laukhtina; Keiichiro Mori; Piotr Radziszewski; Shahrokh F. Shariat; Andrea Necchi; Evanguelos Xylinas; Paolo Gontero; European Association of Urology Young Academic Urologists Urothelial Carcinoma Working Group

doi:10.1016/j.euo.2024.06.005

The Role of Mitomycin C in Intermediate-risk Non-muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis

Pietro Scilipoti
, Aleksander Ślusarczyk
, Mario de Angelis
, Francesco Soria
, Benjamin Pradere
, Wojciech Krajewski
, David D'Andrea
, Andrea Mari
, Francesco Del Giudice
, Renate Pichler
, José Daniel Subiela
, Luca Afferi
, Simone Albisinni
, Laura Mertens
, Ekaterina Laukhtina
, Keiichiro Mori
, Piotr Radziszewski
, Shahrokh F. Shariat
, Andrea Necchi
, Evanguelos Xylinas

Paolo Gontero, European Association of Urology Young Academic Urologists Urothelial Carcinoma Working Group

IRCCS Ospedale San Raffaele
Medical University of Warsaw
University of Turin
La Croix du Sud Hospital
Wrocław Medical University
Medical University of Vienna
University of Florence
University of Rome La Sapienza
Innsbruck Medical University
Hospital Ramon y Cajal
Kantonsspital Luzern
University of Rome Tor Vergata
Netherlands Cancer Institute
The Jikei University School of Medicine
Université Paris Cité
Sorbonne Université

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

BACKGROUND AND OBJECTIVE: Intravesical mitomycin C (MMC) instillations are recommended to prevent recurrence of intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC); however, the optimal regimen and dose are uncertain. Our aim was to assess the effectiveness of adjuvant MMC and compare different MMC regimens in preventing recurrence. METHODS: We performed a comprehensive search in PubMed, Scopus, and Web of Science in November 2023 for studies investigating recurrence-free survival (RFS) among patients with IR-NMIBC who received adjuvant MMC. Prospective trials with different MMC regimens or other intravesical drugs as comparators were considered eligible. KEY FINDINGS AND LIMITATIONS: Overall, 14 studies were eligible for systematic review and 11 for meta-analysis of RFS. Estimates of 1-yr, 2-yr, and 5-yr RFS rates were 84% (95% confidence interval [CI] 79-89%), 75% (95% CI 68-82%), and 51% (95% CI 40-63%) for patients treated with MMC induction plus maintenance, and 88% (95% CI 83-94%), 78% (95% CI 67-89%), and 66% (95% CI 57-75%) for patients treated with bacillus Calmette-Guérin (BCG) maintenance, respectively. Estimates of 2-yr RFS rates for MMC maintenance regimens were 76% (95% CI 69-84%) for 40 mg MMC (2 studies) and 66% (95% CI 60-72%) for 30 mg MMC (4 studies). Among the studies included, BCG maintenance provided comparable 2-yr RFS to 40 mg MMC with maintenance (78% vs 76%). RFS did not differ by MMC maintenance duration (>1 yr vs 1 yr vs <1 yr). CONCLUSIONS AND CLINICAL IMPLICATIONS: MMC induction and maintenance regimens seem to provide short-term RFS rates equivalent to those for BCG maintenance in IR-NMIBC. For adjuvant induction and maintenance, 40 mg of MMC appears to be more effective in preventing recurrence than 30 mg. We did not observe an RFS benefit for longer maintenance regimens. PATIENT SUMMARY: For patients with intermediate-risk non-muscle-invasive bladder cancer, bladder treatments with a solution of a drug called mitomycin C (MMC) seem to be as effective as BCG (bacillus Calmette-Guérin) in preventing recurrence after tumor removal. Further trials are needed for stronger evidence on the best MMC dose and treatment time.

Original language	English
Pages (from-to)	1293-1302
Journal	European Urology Oncology
Volume	7
Issue number	6
DOIs	https://doi.org/10.1016/j.euo.2024.06.005
Publication status	Published - 1 Dec 2024

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SDG 3 Good Health and Well-being

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10.1016/j.euo.2024.06.005

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Scilipoti, P., Ślusarczyk, A., de Angelis, M., Soria, F., Pradere, B., Krajewski, W., D'Andrea, D., Mari, A., Giudice, F. D., Pichler, R., Subiela, J. D., Afferi, L., Albisinni, S., Mertens, L., Laukhtina, E., Mori, K., Radziszewski, P., Shariat, S. F., Necchi, A., ... European Association of Urology Young Academic Urologists Urothelial Carcinoma Working Group (2024). The Role of Mitomycin C in Intermediate-risk Non-muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis. European Urology Oncology, 7(6), 1293-1302. https://doi.org/10.1016/j.euo.2024.06.005

@article{29b56bd38f84440c99bbb55ad21e3c66,

title = "The Role of Mitomycin C in Intermediate-risk Non-muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis",

abstract = "BACKGROUND AND OBJECTIVE: Intravesical mitomycin C (MMC) instillations are recommended to prevent recurrence of intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC); however, the optimal regimen and dose are uncertain. Our aim was to assess the effectiveness of adjuvant MMC and compare different MMC regimens in preventing recurrence. METHODS: We performed a comprehensive search in PubMed, Scopus, and Web of Science in November 2023 for studies investigating recurrence-free survival (RFS) among patients with IR-NMIBC who received adjuvant MMC. Prospective trials with different MMC regimens or other intravesical drugs as comparators were considered eligible. KEY FINDINGS AND LIMITATIONS: Overall, 14 studies were eligible for systematic review and 11 for meta-analysis of RFS. Estimates of 1-yr, 2-yr, and 5-yr RFS rates were 84\% (95\% confidence interval [CI] 79-89\%), 75\% (95\% CI 68-82\%), and 51\% (95\% CI 40-63\%) for patients treated with MMC induction plus maintenance, and 88\% (95\% CI 83-94\%), 78\% (95\% CI 67-89\%), and 66\% (95\% CI 57-75\%) for patients treated with bacillus Calmette-Gu{\'e}rin (BCG) maintenance, respectively. Estimates of 2-yr RFS rates for MMC maintenance regimens were 76\% (95\% CI 69-84\%) for 40 mg MMC (2 studies) and 66\% (95\% CI 60-72\%) for 30 mg MMC (4 studies). Among the studies included, BCG maintenance provided comparable 2-yr RFS to 40 mg MMC with maintenance (78\% vs 76\%). RFS did not differ by MMC maintenance duration (>1 yr vs 1 yr vs <1 yr). CONCLUSIONS AND CLINICAL IMPLICATIONS: MMC induction and maintenance regimens seem to provide short-term RFS rates equivalent to those for BCG maintenance in IR-NMIBC. For adjuvant induction and maintenance, 40 mg of MMC appears to be more effective in preventing recurrence than 30 mg. We did not observe an RFS benefit for longer maintenance regimens. PATIENT SUMMARY: For patients with intermediate-risk non-muscle-invasive bladder cancer, bladder treatments with a solution of a drug called mitomycin C (MMC) seem to be as effective as BCG (bacillus Calmette-Gu{\'e}rin) in preventing recurrence after tumor removal. Further trials are needed for stronger evidence on the best MMC dose and treatment time.",

author = "Pietro Scilipoti and Aleksander {\'S}lusarczyk and \{de Angelis\}, Mario and Francesco Soria and Benjamin Pradere and Wojciech Krajewski and David D'Andrea and Andrea Mari and Giudice, \{Francesco Del\} and Renate Pichler and Subiela, \{Jos{\'e} Daniel\} and Luca Afferi and Simone Albisinni and Laura Mertens and Ekaterina Laukhtina and Keiichiro Mori and Piotr Radziszewski and Shariat, \{Shahrokh F.\} and Andrea Necchi and Evanguelos Xylinas and Paolo Gontero and \{European Association of Urology Young Academic Urologists Urothelial Carcinoma Working Group\} and Morgan Roupr{\^e}t and Francesco Montorsi and Alberto Briganti and Marco Moschini",

year = "2024",

month = dec,

day = "1",

doi = "10.1016/j.euo.2024.06.005",

language = "English",

volume = "7",

pages = "1293--1302",

journal = "European Urology Oncology",

issn = "2588-9311",

publisher = "Elsevier BV",

number = "6",

}

Scilipoti, P, Ślusarczyk, A, de Angelis, M, Soria, F, Pradere, B, Krajewski, W, D'Andrea, D, Mari, A, Giudice, FD, Pichler, R, Subiela, JD, Afferi, L, Albisinni, S, Mertens, L, Laukhtina, E, Mori, K, Radziszewski, P, Shariat, SF, Necchi, A, Xylinas, E, Gontero, P & European Association of Urology Young Academic Urologists Urothelial Carcinoma Working Group 2024, 'The Role of Mitomycin C in Intermediate-risk Non-muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis', European Urology Oncology, vol. 7, no. 6, pp. 1293-1302. https://doi.org/10.1016/j.euo.2024.06.005

TY - JOUR

T1 - The Role of Mitomycin C in Intermediate-risk Non-muscle-invasive Bladder Cancer

T2 - A Systematic Review and Meta-analysis

AU - Scilipoti, Pietro

AU - Ślusarczyk, Aleksander

AU - de Angelis, Mario

AU - Soria, Francesco

AU - Pradere, Benjamin

AU - Krajewski, Wojciech

AU - D'Andrea, David

AU - Mari, Andrea

AU - Giudice, Francesco Del

AU - Pichler, Renate

AU - Subiela, José Daniel

AU - Afferi, Luca

AU - Albisinni, Simone

AU - Mertens, Laura

AU - Laukhtina, Ekaterina

AU - Mori, Keiichiro

AU - Radziszewski, Piotr

AU - Shariat, Shahrokh F.

AU - Necchi, Andrea

AU - Xylinas, Evanguelos

AU - Gontero, Paolo

AU - European Association of Urology Young Academic Urologists Urothelial Carcinoma Working Group

AU - Rouprêt, Morgan

AU - Montorsi, Francesco

AU - Briganti, Alberto

AU - Moschini, Marco

PY - 2024/12/1

Y1 - 2024/12/1

N2 - BACKGROUND AND OBJECTIVE: Intravesical mitomycin C (MMC) instillations are recommended to prevent recurrence of intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC); however, the optimal regimen and dose are uncertain. Our aim was to assess the effectiveness of adjuvant MMC and compare different MMC regimens in preventing recurrence. METHODS: We performed a comprehensive search in PubMed, Scopus, and Web of Science in November 2023 for studies investigating recurrence-free survival (RFS) among patients with IR-NMIBC who received adjuvant MMC. Prospective trials with different MMC regimens or other intravesical drugs as comparators were considered eligible. KEY FINDINGS AND LIMITATIONS: Overall, 14 studies were eligible for systematic review and 11 for meta-analysis of RFS. Estimates of 1-yr, 2-yr, and 5-yr RFS rates were 84% (95% confidence interval [CI] 79-89%), 75% (95% CI 68-82%), and 51% (95% CI 40-63%) for patients treated with MMC induction plus maintenance, and 88% (95% CI 83-94%), 78% (95% CI 67-89%), and 66% (95% CI 57-75%) for patients treated with bacillus Calmette-Guérin (BCG) maintenance, respectively. Estimates of 2-yr RFS rates for MMC maintenance regimens were 76% (95% CI 69-84%) for 40 mg MMC (2 studies) and 66% (95% CI 60-72%) for 30 mg MMC (4 studies). Among the studies included, BCG maintenance provided comparable 2-yr RFS to 40 mg MMC with maintenance (78% vs 76%). RFS did not differ by MMC maintenance duration (>1 yr vs 1 yr vs <1 yr). CONCLUSIONS AND CLINICAL IMPLICATIONS: MMC induction and maintenance regimens seem to provide short-term RFS rates equivalent to those for BCG maintenance in IR-NMIBC. For adjuvant induction and maintenance, 40 mg of MMC appears to be more effective in preventing recurrence than 30 mg. We did not observe an RFS benefit for longer maintenance regimens. PATIENT SUMMARY: For patients with intermediate-risk non-muscle-invasive bladder cancer, bladder treatments with a solution of a drug called mitomycin C (MMC) seem to be as effective as BCG (bacillus Calmette-Guérin) in preventing recurrence after tumor removal. Further trials are needed for stronger evidence on the best MMC dose and treatment time.

AB - BACKGROUND AND OBJECTIVE: Intravesical mitomycin C (MMC) instillations are recommended to prevent recurrence of intermediate-risk non-muscle-invasive bladder cancer (IR-NMIBC); however, the optimal regimen and dose are uncertain. Our aim was to assess the effectiveness of adjuvant MMC and compare different MMC regimens in preventing recurrence. METHODS: We performed a comprehensive search in PubMed, Scopus, and Web of Science in November 2023 for studies investigating recurrence-free survival (RFS) among patients with IR-NMIBC who received adjuvant MMC. Prospective trials with different MMC regimens or other intravesical drugs as comparators were considered eligible. KEY FINDINGS AND LIMITATIONS: Overall, 14 studies were eligible for systematic review and 11 for meta-analysis of RFS. Estimates of 1-yr, 2-yr, and 5-yr RFS rates were 84% (95% confidence interval [CI] 79-89%), 75% (95% CI 68-82%), and 51% (95% CI 40-63%) for patients treated with MMC induction plus maintenance, and 88% (95% CI 83-94%), 78% (95% CI 67-89%), and 66% (95% CI 57-75%) for patients treated with bacillus Calmette-Guérin (BCG) maintenance, respectively. Estimates of 2-yr RFS rates for MMC maintenance regimens were 76% (95% CI 69-84%) for 40 mg MMC (2 studies) and 66% (95% CI 60-72%) for 30 mg MMC (4 studies). Among the studies included, BCG maintenance provided comparable 2-yr RFS to 40 mg MMC with maintenance (78% vs 76%). RFS did not differ by MMC maintenance duration (>1 yr vs 1 yr vs <1 yr). CONCLUSIONS AND CLINICAL IMPLICATIONS: MMC induction and maintenance regimens seem to provide short-term RFS rates equivalent to those for BCG maintenance in IR-NMIBC. For adjuvant induction and maintenance, 40 mg of MMC appears to be more effective in preventing recurrence than 30 mg. We did not observe an RFS benefit for longer maintenance regimens. PATIENT SUMMARY: For patients with intermediate-risk non-muscle-invasive bladder cancer, bladder treatments with a solution of a drug called mitomycin C (MMC) seem to be as effective as BCG (bacillus Calmette-Guérin) in preventing recurrence after tumor removal. Further trials are needed for stronger evidence on the best MMC dose and treatment time.

UR - https://www.scopus.com/pages/publications/85210667814

UR - https://www.ncbi.nlm.nih.gov/pubmed/38902138

U2 - 10.1016/j.euo.2024.06.005

DO - 10.1016/j.euo.2024.06.005

M3 - Article

C2 - 38902138

SN - 2588-9311

VL - 7

SP - 1293

EP - 1302

JO - European Urology Oncology

JF - European Urology Oncology

IS - 6

ER -

The Role of Mitomycin C in Intermediate-risk Non-muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis

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