42980c3dd74a8557399c116e01943842 302806.pdf b970d2424bc756a88d4cddc88f6ff4b9df4b7faf 302806.pdf 3a4e8e9a90540d0e0c4719f72c7a862d3c2976c252bd78a36c1a3dccec05ab9d 302806.pdf Title: 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 Subject: 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: 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: 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: 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. Keywords: bladder cancer; non-muscle invasive bladder cancer; recurrence rate; BCG immunotherapy; BCG strain; network meta-analysis Author: Francesco Del Giudice, Vincenzo Asero, Eugenio Bologna, Carlo Maria Scornajenghi, Dalila Carino, Virginia Dolci, Pietro Viscuso, Stefano Salciccia, Alessandro Sciarra, David D’Andrea, Benjamin Pradere, Marco Moschini, Andrea Mari, Simone Albisinni, Wojciech Krajewski, Tomasz Szydełko, Bartosz Małkiewicz, Łukasz Nowak, Ekaterina Laukhtina, Andrea Gallioli, Laura S. Mertens, Gautier Marcq, Alessia Cimadamore, Luca Afferi, Francesco Soria, Keiichiro Mori, Karl Heinrich Tully, Renate Pichler, Matteo Ferro, Octavian Sabin Tataru, Riccardo Autorino, Simone Crivellaro, Felice Crocetto, Gian Maria Busetto, Satvir Basran, Michael L. Eisenberg, Benjamin Inbeh Chung and Ettore De Berardinis Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Mar 23 12:51:53 2023 CET ModDate: Thu Mar 23 13:24:29 2023 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 25 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2245462 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- NLBGIG+URWPalladioL-Bold Type 1 Custom yes yes no 10 0 BHNNQC+URWPalladioL-Roma Type 1 Custom yes yes no 15 0 VUMJWU+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 PJALPN+VnURWPalladioL Type 1 Custom yes yes no 23 0 BTFGED+VnURWPalladioL-Bold Type 1 Custom yes yes no 28 0 LCJEVJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 47 0 VDNGGL+CMSY10 Type 1 Builtin yes yes no 69 0 EFMOKI+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 113 0 EFMOKJ+PalatinoLinotype CID TrueType Identity-H yes yes yes 116 0 EFMOLK+PalatinoLinotype TrueType WinAnsi yes yes no 122 0 EFMOLM+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 125 0 EFMOKI+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 136 0 EFMOLK+PalatinoLinotype TrueType WinAnsi yes yes no 139 0 EFMOLM+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 142 0 EFMOKI+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 158 0 EFMOLK+PalatinoLinotype TrueType WinAnsi yes yes no 161 0 EFMOLM+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 164 0 CKBPVA+EURM10 Type 1 Builtin yes yes no 185 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-11-14 02:53:58 CET RepresentationInformation: 302806.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2024-11-13 14:06:31 CET Size: 2245462 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 864 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Methods Destination: section.2 Children: Item: Title: Evidence Acquisition Destination: subsection.2.1 Item: Title: Selection of the Studies and Criteria of Inclusion Destination: subsection.2.2 Item: Title: Assessment of Quality for Studies Included and Statistical Analysis Destination: subsection.2.3 Item: Title: Results Destination: section.3 Children: Item: Title: Search Results Destination: subsection.3.1 Item: Title: Characteristics of The Populations, Study Design, and Location Destination: subsection.3.2 Item: Title: BCG-Specific Characteristics: Stains, Schedule, and Dose Destination: subsection.3.3 Children: Item: Title: BC Recurrence Rate Meta-Analysis Destination: subsubsection.3.3.1 Item: Title: BC Recurrence Rate by 3-y RFS Endpoints and BCG Strain Destination: subsubsection.3.3.2 Item: Title: BC Recurrence Rate for >3-y RFS Endpoint and BCG Strain Destination: subsubsection.3.3.3 Item: Title: Evidence Structure of Network Meta-Analysis for BCG Strain Comparison Destination: subsubsection.3.3.4 Item: Title: Network Meta-Analysis for Risk of BC Recurrence among Intravesical BCG Strains Destination: subsubsection.3.3.5 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: 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 Author: Francesco Del Giudice, Vincenzo Asero, Eugenio Bologna, Carlo Maria Scornajenghi, Dalila Carino, Virginia Dolci, Pietro Viscuso, Stefano Salciccia, Alessandro Sciarra, David D’Andrea, Benjamin Pradere, Marco Moschini, Andrea Mari, Simone Albisinni, Wojciech Krajewski, Tomasz Szydełko, Bartosz Małkiewicz, Łukasz Nowak, Ekaterina Laukhtina, Andrea Gallioli, Laura S. Mertens, Gautier Marcq, Alessia Cimadamore, Luca Afferi, Francesco Soria, Keiichiro Mori, Karl Heinrich Tully, Renate Pichler, Matteo Ferro, Octavian Sabin Tataru, Riccardo Autorino, Simone Crivellaro, Felice Crocetto, Gian Maria Busetto, Satvir Basran, Michael L. Eisenberg, Benjamin Inbeh Chung and Ettore De Berardinis Subject: 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: 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: 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: 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. 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401, 381, 412 Annotation: Subtype: Link Rect: 388, 401, 424, 412 Checksum: d8cd7381 Type: CRC32 Checksum: 42980c3dd74a8557399c116e01943842 Type: MD5 Checksum: b970d2424bc756a88d4cddc88f6ff4b9df4b7faf Type: SHA-1 Checksum: 3a4e8e9a90540d0e0c4719f72c7a862d3c2976c252bd78a36c1a3dccec05ab9d Type: SHA-256