128b0fd89924dca1484dc89611cbac45 pmc_33567656.pdf d1c7a29c4874d9658d2965a9deccccc42f86fd7f pmc_33567656.pdf 28c973b873ad2d9512f38d3953a3035296b9c7efed59760585f83c555c7a90ff pmc_33567656.pdf Title: Impact of Adjuvant Chemotherapy on Survival of Patients with Advanced Residual Disease at Radical Cystectomy following Neoadjuvant Chemotherapy: Systematic Review and Meta-Analysis Subject: Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph-node dissection is the standard treatment for cT2-4a cN0 cM0 muscle-invasive bladder cancer (MIBC). Despite the significant improvement of primary-tumor downstaging with NAC, up to 50% of patients are eventually found to have advanced residual disease (pT3–T4 and/or histopathologically confirmed nodal metastases (pN+)) at RC. Currently, there is no established standard of care in such cases. The aim of this systematic review and meta-analysis was to assess differences in survival rates between patients with pT3–T4 and/or pN+ MIBC who received NAC and surgery followed by adjuvant chemotherapy (AC), and patients without AC. Materials and Methods: A systematic search was conducted in accordance with the PRISMA statement using the Medline, Embase, and Cochrane Library databases. The last search was performed on 12 November 2020. The primary end point was overall survival (OS) and the secondary end point was disease-specific survival (DSS). Results: We identified 2124 articles, of which 6 were selected for qualitative and quantitative analyses. Of a total of 3096 participants in the included articles, 2355 (76.1%) were in the surveillance group and 741 (23.9%) received AC. The use of AC was associated with significantly better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75–0.94; p = 0.002) and DSS (HR 0.56, 95% CI 0.32–0.99; p = 0.05). Contrary to the main analysis, in the subgroup analysis including only patients with pN+, AC was not significantly associated with better OS compared to the surveillance group (HR 0.89, 95% CI 0.58–1.35; p = 0.58). Conclusions: The administration of AC in patients with MIBC and pT3–T4 residual disease after NAC might have a positive impact on OS and DSS. However, this may not apply to N+ patients. Keywords: adjuvant chemotherapy; muscle-invasive bladder cancer; neoadjuvant chemotherapy Author: Wojciech Krajewski, Łukasz Nowak, Marco Moschini, Sławomir Poletajew, Joanna Chorbińska, Andrea Necchi, Francesco Montorsi, Alberto Briganti, Rafael Sanchez-Salas, Shahrokh F Shariat, Juan Palou, Marek Babjuk, Jeremy YC Teoh, Francesco Soria, Benjamin Pradere, Paola Irene Ornaghi, Aleksandra Pawlak, Janusz Dembowski and Romuald Zdrojowy Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Tue Feb 9 07:09:09 2021 CET ModDate: Tue Feb 9 07:15:16 2021 CET Custom Metadata: no Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 11 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 2575044 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- EVELEL+VnURWPalladioL Type 1 Custom yes yes no 10 0 BAFROJ+URWPalladioL-Ital Type 1 Custom yes yes no 15 0 KKWYSC+URWPalladioL-Bold Type 1 Custom yes yes no 20 0 IMLKLR+URWPalladioL-Roma Type 1 Custom yes yes no 24 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 32 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 35 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 57 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 61 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 65 0 IKKWKP+CMSY10 Type 1 Builtin yes yes no 80 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2024-10-02 03:31:25 CEST RepresentationInformation: pmc_33567656.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2023-03-31 12:08:50 CEST Size: 2575044 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 249 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: section.1 Item: Title: Materials and Methods Destination: section.2 Children: Item: Title: Search Strategy Destination: subsection.2.1 Item: Title: Inclusion Criteria Destination: subsection.2.2 Item: Title: Data Extraction Destination: subsection.2.3 Item: Title: Quality and Risk-of-Bias Assessment Destination: subsection.2.4 Item: Title: Statistical Analysis Destination: subsection.2.5 Item: Title: Results Destination: section.3 Children: Item: Title: Study Identification and Quality Assessment Destination: subsection.3.1 Item: Title: Clinical Characteristics and Pathological Data Destination: subsection.3.2 Item: Title: Risk-of-Bias Assessment Destination: subsection.3.3 Item: Title: Meta-Analysis Results Destination: subsection.3.4 Item: Title: Discussion Destination: section.4 Item: Title: Conclusions Destination: section.5 Item: Title: References Destination: section.5 Info: Title: Impact of Adjuvant Chemotherapy on Survival of Patients with Advanced Residual Disease at Radical Cystectomy following Neoadjuvant Chemotherapy: Systematic Review and Meta-Analysis Author: しはなっどづっと〠かひちなづぷびにど〬〠ㅁふにちびぺ〠ぎはぷちに〬〠きちひっは〠きはびっとどのど〬〠こㅂちぷはねどひ〠ぐはぬづぴちなづぷ〬〠おはちののち〠ぃとはひぢどㅄびにち〬〠ぁのつひづち〠ぎづっっとど〬〠うひちのっづびっは〠きはのぴはひびど〬〠ぁぬぢづひぴは〠あひどでちのぴど〬〠げちてちづぬ〠こちのっとづぺ〭こちぬちび〬〠ことちとひはにと〠う〠ことちひどちぴ〬〠おふちの〠ぐちぬはふ〬〠きちひづに〠あちぢなふに〬〠おづひづねべ〠すぃ〠ごづはと〬〠うひちのっづびっは〠こはひどち〬〠あづのなちねどの〠ぐひちつづひづ〬〠ぐちはぬち〠ぉひづのづ〠くひのちでとど〬〠ぁぬづにびちのつひち〠ぐちぷぬちに〬〠おちのふびぺ〠いづねぢはぷびにど〠ちのつ〠げはねふちぬつ〠ずつひはなはぷべ Subject: Background: Cisplatin-based neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) with pelvic lymph-node dissection is the standard treatment for cT2-4a cN0 cM0 muscle-invasive bladder cancer (MIBC). Despite the significant improvement of primary-tumor downstaging with NAC, up to 50% of patients are eventually found to have advanced residual disease (pT3 T4 and/or histopathologically confirmed nodal metastases (pN+)) at RC. Currently, there is no established standard of care in such cases. The aim of this systematic review and meta-analysis was to assess differences in survival rates between patients with pT3 T4 and/or pN+ MIBC who received NAC and surgery followed by adjuvant chemotherapy (AC), and patients without AC. Materials and Methods: A systematic search was conducted in accordance with the PRISMA statement using the Medline, Embase, and Cochrane Library databases. The last search was performed on 12 November 2020. The primary end point was overall survival (OS) and the secondary end point was disease-specific survival (DSS). Results: We identified 2124 articles, of which 6 were selected for qualitative and quantitative analyses. Of a total of 3096 participants in the included articles, 2355 (76.1%) were in the surveillance group and 741 (23.9%) received AC. The use of AC was associated with significantly better OS (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.75 0.94; p = 0.002) and DSS (HR 0.56, 95% CI 0.32 0.99; p = 0.05). Contrary to the main analysis, in the subgroup analysis including only patients with pN+, AC was not significantly associated with better OS compared to the surveillance group (HR 0.89, 95% CI 0.58 1.35; p = 0.58). Conclusions: The administration of AC in patients with MIBC and pT3 T4 residual disease after NAC might have a positive impact on OS and DSS. However, this may not apply to N+ patients. 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