Efficacy of Different Bacillus of Calmette-Guérin (BCG) Strains on Recurrence Rates among Intermediate/High-Risk Non-Muscle Invasive Bladder Cancers (NMIBCs): Single-Arm Study Systematic Review, Cumulative and Network Meta-Analysis.

BCG immunotherapy BCG strain bladder cancer network meta-analysis non-muscle invasive bladder cancer recurrence rate

Journal

Cancers
ISSN: 2072-6694
Titre abrégé: Cancers (Basel)
Pays: Switzerland
ID NLM: 101526829

Informations de publication

Date de publication:
23 Mar 2023
Historique:
received: 14 01 2023
revised: 19 03 2023
accepted: 20 03 2023
medline: 14 4 2023
entrez: 13 4 2023
pubmed: 14 4 2023
Statut: epublish

Résumé

In an era of Bacillus of Calmette-Guérin (BCG) shortages, the comparative efficacy from different adjuvant intravesical BCG strains in non-muscle invasive bladder cancer (NMIBC) has not been clearly elucidated. We aim to compare, through a systematic review and meta-analysis, the cumulative BC recurrence rates and the best efficacy profile of worldwide available BCG strains over the last forty years. PubMed, Scopus, Web of Science, Embase, and Cochrane databases were searched from 1982 up to 2022. A meta-analysis of pooled BC recurrence rates was stratified for studies with ≤3-y vs. >3-y recurrence-free survival (RFS) endpoints and the strain of BCG. Sensitivity analysis, sub-group analysis, and meta-regression were implemented to investigate the contribution of moderators to heterogeneity. A random-effect network meta-analysis was performed to compare BCG strains on a multi-treatment level. In total, n = 62 series with n = 15,412 patients in n = 100 study arms and n = 10 different BCG strains were reviewed. BCG Tokyo 172 exhibited the lowest pooled BC recurrence rate among studies with ≤3-y RFS (0.22 (95%CI 0.16-0.28). No clinically relevant difference was noted among strains at >3-y RFS outcomes. Sub-group and meta-regression analyses highlighted the influence of NMIBC risk-group classification and previous intravesical treated categories. Out of the n = 11 studies with n = 7 BCG strains included in the network, BCG RIVM, Tice, and Tokyo 172 presented with the best-predicted probability for efficacy, yet no single strain was significantly superior to another in preventing BC recurrence risk. We did not identify a BCG stain providing a clinically significant lower BC recurrence rate. While these findings might discourage investment in future head-to-head randomized comparison, we were, however, able to highlight some potential enhanced benefits from the genetically different BCG RIVM, Tice, and Tokyo 172. This evidence would support the use of such strains for future BCG trials in NMIBCs.

Sections du résumé

BACKGROUND BACKGROUND
In an era of Bacillus of Calmette-Guérin (BCG) shortages, the comparative efficacy from different adjuvant intravesical BCG strains in non-muscle invasive bladder cancer (NMIBC) has not been clearly elucidated. We aim to compare, through a systematic review and meta-analysis, the cumulative BC recurrence rates and the best efficacy profile of worldwide available BCG strains over the last forty years.
METHODS METHODS
PubMed, Scopus, Web of Science, Embase, and Cochrane databases were searched from 1982 up to 2022. A meta-analysis of pooled BC recurrence rates was stratified for studies with ≤3-y vs. >3-y recurrence-free survival (RFS) endpoints and the strain of BCG. Sensitivity analysis, sub-group analysis, and meta-regression were implemented to investigate the contribution of moderators to heterogeneity. A random-effect network meta-analysis was performed to compare BCG strains on a multi-treatment level.
RESULTS RESULTS
In total, n = 62 series with n = 15,412 patients in n = 100 study arms and n = 10 different BCG strains were reviewed. BCG Tokyo 172 exhibited the lowest pooled BC recurrence rate among studies with ≤3-y RFS (0.22 (95%CI 0.16-0.28). No clinically relevant difference was noted among strains at >3-y RFS outcomes. Sub-group and meta-regression analyses highlighted the influence of NMIBC risk-group classification and previous intravesical treated categories. Out of the n = 11 studies with n = 7 BCG strains included in the network, BCG RIVM, Tice, and Tokyo 172 presented with the best-predicted probability for efficacy, yet no single strain was significantly superior to another in preventing BC recurrence risk.
CONCLUSION CONCLUSIONS
We did not identify a BCG stain providing a clinically significant lower BC recurrence rate. While these findings might discourage investment in future head-to-head randomized comparison, we were, however, able to highlight some potential enhanced benefits from the genetically different BCG RIVM, Tice, and Tokyo 172. This evidence would support the use of such strains for future BCG trials in NMIBCs.

Identifiants

pubmed: 37046598
pii: cancers15071937
doi: 10.3390/cancers15071937
pmc: PMC10093360
pii:
doi:

Types de publication

Journal Article Review

Langues

eng

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Auteurs

Francesco Del Giudice (F)

Department of Maternal-Infant and Urological Sciences, Policlinico Umberto I Hospital, "Sapienza" University of Rome, 00185 Rome, Italy.
Department of Urology, Stanford University School of Medicine, Stanford, CA 94305-5101, USA.

Vincenzo Asero (V)

Department of Maternal-Infant and Urological Sciences, Policlinico Umberto I Hospital, "Sapienza" University of Rome, 00185 Rome, Italy.

Eugenio Bologna (E)

Department of Maternal-Infant and Urological Sciences, Policlinico Umberto I Hospital, "Sapienza" University of Rome, 00185 Rome, Italy.

Carlo Maria Scornajenghi (CM)

Department of Maternal-Infant and Urological Sciences, Policlinico Umberto I Hospital, "Sapienza" University of Rome, 00185 Rome, Italy.

Dalila Carino (D)

Department of Maternal-Infant and Urological Sciences, Policlinico Umberto I Hospital, "Sapienza" University of Rome, 00185 Rome, Italy.

Virginia Dolci (V)

Department of Maternal-Infant and Urological Sciences, Policlinico Umberto I Hospital, "Sapienza" University of Rome, 00185 Rome, Italy.

Pietro Viscuso (P)

Department of Maternal-Infant and Urological Sciences, Policlinico Umberto I Hospital, "Sapienza" University of Rome, 00185 Rome, Italy.

Stefano Salciccia (S)

Department of Maternal-Infant and Urological Sciences, Policlinico Umberto I Hospital, "Sapienza" University of Rome, 00185 Rome, Italy.

Alessandro Sciarra (A)

Department of Maternal-Infant and Urological Sciences, Policlinico Umberto I Hospital, "Sapienza" University of Rome, 00185 Rome, Italy.

David D'Andrea (D)

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1030 Vienna, Austria.

Benjamin Pradere (B)

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1030 Vienna, Austria.
Department of Urology, La Croix du Sud Hospital, 31130 Quint-Fonsegrives, France.

Marco Moschini (M)

Department of Urology and Division of Experimental Oncology, Urological Research Institute, Vita-Salute San Raffaele, 20132 Milan, Italy.

Andrea Mari (A)

Department of Experimental and Clinical Medicine, University of Florence-Unit of Oncologic Minimally-Invasive Urology and Andrology, Careggi Hospital, 50134 Florence, Italy.

Simone Albisinni (S)

Urology Unit, Department of Surgical Sciences, Tor Vergata University Hospital, University of Rome Tor Vergata, 00133 Rome, Italy.

Wojciech Krajewski (W)

Department of Minimally Invasive and Robotic Urology, Wrocław Medical University, 50-367 Wrocław, Poland.

Tomasz Szydełko (T)

Department of Minimally Invasive and Robotic Urology, Wrocław Medical University, 50-367 Wrocław, Poland.

Bartosz Małkiewicz (B)

Department of Minimally Invasive and Robotic Urology, Wrocław Medical University, 50-367 Wrocław, Poland.

Łukasz Nowak (Ł)

Department of Minimally Invasive and Robotic Urology, Wrocław Medical University, 50-367 Wrocław, Poland.

Ekaterina Laukhtina (E)

Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, 1030 Vienna, Austria.
Institute for Urology and Reproductive Health, Sechenov University, 119435 Moscow, Russia.

Andrea Gallioli (A)

Department of Urology, Fundacio Puigvert, 16444 Barcelona, Spain.

Laura S Mertens (LS)

Department of Urology, The Netherlands Cancer Institute, 1066 Amsterdam, The Netherlands.

Gautier Marcq (G)

Urology Department, Claude Huriez Hospital, CHU Lille, 59000 Lille, France.
Cancer Heterogeneity Plasticity and Resistance to Therapies, UMR9020-U1277-CANTHER, Institut Pasteur de LilleCHU Lille, Inserm, CNRS University of Lille, 59000 Lille, France.

Alessia Cimadamore (A)

Department of Medical Area (DAME), Institute of Pathological Anatomy, University of Udine, 33100 Udine, Italy.

Luca Afferi (L)

Department of Urology, Luzerner Kantonsspital, 6004 Luzern, Switzerland.

Francesco Soria (F)

Urology Division, Department of Surgical Sciences, University of Studies of Torino, 10124 Turin, Italy.

Keiichiro Mori (K)

Department of Urology, The Jikei University School of Medicine, Nishi-Shimbashi, Minato-ku, Tokyo 105-8461, Japan.

Karl Heinrich Tully (KH)

Department of Urology and Neurourology, Marien Hospital Herne, Ruhr-University Bochum, 44780 Herne, Germany.

Renate Pichler (R)

Department of Urology, Comprehensive Cancer Center Innsbruck, Medical University of Innsbruck, 6020 Innsbruck, Austria.

Matteo Ferro (M)

Division of Urology, European Institute of Oncology, IRCCS, 20141 Milan, Italy.

Octavian Sabin Tataru (OS)

Department of Simulation Applied in Medicine, The Institution Organizing University Doctoral Studies (I.O.S.U.D.), George Emil Palade University of Medicine, Pharmacy, Sciences, and Technology, 540142 Târgu Mureș, Romania.

Riccardo Autorino (R)

Department of Urology, Rush University Medical Center, Chicago, IL 60612, USA.

Simone Crivellaro (S)

Health Sciences System, Department of Urology, University of Illinois Hospital e Camp, Chicago, IL 60612, USA.

Felice Crocetto (F)

Reproductive Sciences and Odontostomatology, Urology Unit, Department of Neurosciences, University of Naples "Federico II", 80138 Naples, Italy.

Gian Maria Busetto (GM)

Department of Urology and Organ Transplantation, University of Foggia, 71122 Foggia, Italy.

Satvir Basran (S)

Department of Urology, Stanford University School of Medicine, Stanford, CA 94305-5101, USA.

Michael L Eisenberg (ML)

Department of Urology, Stanford University School of Medicine, Stanford, CA 94305-5101, USA.

Benjamin Inbeh Chung (BI)

Department of Urology, Stanford University School of Medicine, Stanford, CA 94305-5101, USA.

Ettore De Berardinis (E)

Department of Maternal-Infant and Urological Sciences, Policlinico Umberto I Hospital, "Sapienza" University of Rome, 00185 Rome, Italy.

Classifications MeSH