{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T05:05:02Z","timestamp":1766466302625,"version":"3.37.3"},"reference-count":40,"publisher":"BMJ","funder":[{"DOI":"10.13039\/501100003495","name":"Hessisches Ministerium f\u00fcr Wissenschaft und Kunst","doi-asserted-by":"publisher","award":["III L 5 \u2013 519\/03\/03.001 \u2013 (0015)"],"award-info":[{"award-number":["III L 5 \u2013 519\/03\/03.001 \u2013 (0015)"]}],"id":[{"id":"10.13039\/501100003495","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"Deutsche Krebshilfe","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Clin Pathol"],"accepted":{"date-parts":[[2023,10,30]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Adjuvant chemotherapy after radical cystectomy can reduce the risk of recurrence and death in advanced muscle-invasive urothelial bladder cancer (MIBC). Molecular subtypes have been shown to be associated with survival. However, their predictive value to guide treatment decisions is controversial and data to use subtypes as guidance for adjuvant chemotherapy is sparse. We aimed to assess survival rates based on MIBC consensus molecular subtypes with and without adjuvant chemotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Gene expression profiles of 143 patients with MIBC undergoing radical cystectomy were determined from formalin-fixed, paraffin-embedded specimen to assign consensus molecular subtypes. Expression of programmed cell death ligand-1 (PD-L1) and immune cell infiltration were determined using multiplex immunofluorescence. Matched-pair analysis was performed to evaluate the effect of adjuvant chemotherapy on overall survival (OS) for molecular subtypes applying Kaplan-Meier and Cox regression survival analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Samples were luminal papillary: 9.1% (n=13), luminal non-specified: 6.3% (n=9), luminal unstable: 4.9% (n=7), stroma-rich: 27.9% (n=40), basal\/squamous (Ba\/Sq): 48.9% (n=70) and neuroendocrine-like (NE-like): 2.8% (n=4). Ba\/Sq tumours had the highest concentration of PD-L1+ tumour\u2009and immune cells. Patients with luminal subtypes had better OS than those with NE-like (HR 0.2, 95% CI 0.1 to 0.7, p&lt;0.05) and Ba\/Sq (HR 0.5, 95% CI 0.2 to 0.9, p&lt;0.05). No survival benefit with adjuvant chemotherapy was observed for luminal tumours, whereas Ba\/Sq had significantly improved survival rates with adjuvant chemotherapy. Retrospective design and sample size are the main limitations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Consensus molecular subtypes can be used to stratify patients with MIBC. Luminal tumours have the best prognosis and less benefit when receiving adjuvant chemotherapy compared with Ba\/Sq tumours.<\/jats:p><\/jats:sec>","DOI":"10.1136\/jcp-2023-208973","type":"journal-article","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T18:22:53Z","timestamp":1700590973000},"page":"jcp-2023-208973","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":8,"title":["Impact of consensus molecular subtypes on survival with and without adjuvant chemotherapy in muscle-invasive urothelial bladder cancer"],"prefix":"10.1136","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7828-3950","authenticated-orcid":false,"given":"Florestan J","family":"Koll","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"D\u00f6ring","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leon","family":"Herwig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedikt","family":"Hoeh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mike","family":"Wenzel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Cano Garcia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Severine","family":"Banek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis","family":"Kluth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jens","family":"K\u00f6llermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andreas","family":"Weigert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Felix K-H","family":"Chun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Wild","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henning","family":"Reis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2023,11,21]]},"reference":[{"key":"2024053002462755000_jcp-2023-208973v1.1","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/s41585-020-0304-1","article-title":"Genomic heterogeneity in bladder cancer: challenges and possible solutions to improve outcomes","volume":"17","author":"Meeks","year":"2020","journal-title":"Nat Rev Urol"},{"key":"2024053002462755000_jcp-2023-208973v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2020.03.055"},{"key":"2024053002462755000_jcp-2023-208973v1.3","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1097\/JU.0000000000002261","article-title":"Patients with muscle-invasive bladder cancer with Nonluminal subtype derive greatest benefit from platinum based Neoadjuvant chemotherapy","volume":"207","author":"Lotan","year":"2022","journal-title":"J Urol"},{"key":"2024053002462755000_jcp-2023-208973v1.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.09.007"},{"key":"2024053002462755000_jcp-2023-208973v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2017.03.030"},{"key":"2024053002462755000_jcp-2023-208973v1.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2019.09.006"},{"key":"2024053002462755000_jcp-2023-208973v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2014.01.009"},{"key":"2024053002462755000_jcp-2023-208973v1.8","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1002\/ijc.33809","article-title":"A quantitative polymerase chain reaction based method for molecular subtype classification of urinary bladder cancer-stromal gene expressions show higher Prognostic values than intrinsic tumor genes","volume":"150","author":"Olah","year":"2022","journal-title":"Int J Cancer"},{"key":"2024053002462755000_jcp-2023-208973v1.9","doi-asserted-by":"crossref","first-page":"5222","DOI":"10.1002\/cam4.5324","article-title":"Predictive value of molecular subtypes and Apobec3G for adjuvant chemotherapy in urothelial bladder cancer","volume":"12","author":"Olah","year":"2023","journal-title":"Cancer Med"},{"key":"2024053002462755000_jcp-2023-208973v1.10","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1016\/j.eururo.2021.10.035","article-title":"Different responses to neoadjuvant chemotherapy in urothelial carcinoma molecular subtypes","volume":"81","author":"Sj\u00f6dahl","year":"2022","journal-title":"Eur Urol"},{"key":"2024053002462755000_jcp-2023-208973v1.11","doi-asserted-by":"crossref","first-page":"4858","DOI":"10.1038\/s41467-020-18640-0","article-title":"Molecular correlates of cisplatin-based chemotherapy response in muscle invasive bladder cancer by integrated multi-omics analysis","volume":"11","author":"Taber","year":"2020","journal-title":"Nat Commun"},{"key":"2024053002462755000_jcp-2023-208973v1.12","unstructured":"Board WCoTE . Urinary and Male Genital Tumours - WHO Classification of Tumours 5th Edition. IARC Publications, 2022."},{"key":"2024053002462755000_jcp-2023-208973v1.13","doi-asserted-by":"crossref","first-page":"875142","DOI":"10.3389\/fmed.2022.875142","article-title":"Ck5\/6 and gata3 defined phenotypes of muscle-invasive bladder cancer: impact in adjuvant chemotherapy and molecular Subtyping of negative cases","volume":"9","author":"Koll","year":"2022","journal-title":"Front Med (Lausanne)"},{"key":"2024053002462755000_jcp-2023-208973v1.14","doi-asserted-by":"crossref","DOI":"10.3390\/cells12040589","article-title":"Overexpression of Kmt9Alpha is associated with aggressive basal-like muscle-invasive bladder cancer","volume":"12","author":"Koll","year":"2023","journal-title":"Cells"},{"key":"2024053002462755000_jcp-2023-208973v1.15","doi-asserted-by":"crossref","DOI":"10.1186\/s12967-023-03949-3","article-title":"Tumor-associated Macrophages and Tregs influence and represent immune cell infiltration of muscle-invasive bladder cancer and predict prognosis","volume":"21","author":"Koll","year":"2023","journal-title":"J Transl Med"},{"key":"2024053002462755000_jcp-2023-208973v1.16","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12764"},{"key":"2024053002462755000_jcp-2023-208973v1.17","doi-asserted-by":"crossref","DOI":"10.1186\/s12885-023-11016-9","article-title":"Optimizing identification of consensus molecular subtypes in muscle-invasive bladder cancer: a comparison of two sequencing methods and gene SETS using FFPE specimens","volume":"23","author":"Koll","year":"2023","journal-title":"BMC Cancer"},{"key":"2024053002462755000_jcp-2023-208973v1.18","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1038\/s41374-020-0446-z","article-title":"3' MACE RNA-sequencing allows for Transcriptome profiling in human tissue samples after long-term storage","volume":"100","author":"Boneva","year":"2020","journal-title":"Lab Invest"},{"key":"2024053002462755000_jcp-2023-208973v1.19","unstructured":"RCT . R A language and environment for statistical computing. n.d. Available: https:\/\/www.r-project.org"},{"key":"2024053002462755000_jcp-2023-208973v1.20","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.eururo.2021.09.028","article-title":"Advanced bladder cancer meta-analysis collaborators G. adjuvant chemotherapy for muscle-invasive bladder cancer: a systematic review and meta-analysis of individual participant data from randomised controlled trials","volume":"81","author":"Burdett","year":"2022","journal-title":"Eur Urol"},{"key":"2024053002462755000_jcp-2023-208973v1.21","first-page":"957","article-title":"Adjuvant Nivolumab in muscle-invasive urothelial carcinoma. reply","volume":"385","author":"Bajorin","year":"2021","journal-title":"N Engl J Med"},{"key":"2024053002462755000_jcp-2023-208973v1.22","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1318376111"},{"key":"2024053002462755000_jcp-2023-208973v1.23","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-12-0077-T"},{"key":"2024053002462755000_jcp-2023-208973v1.24","doi-asserted-by":"publisher","DOI":"10.1038\/srep10957"},{"key":"2024053002462755000_jcp-2023-208973v1.25","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.euf.2021.04.007","article-title":"Artificial intelligence-based detection of Fgfr3 mutational status directly from routine histology in bladder cancer: a possible preselection for molecular testing?","volume":"8","author":"Loeffler","year":"2022","journal-title":"Eur Urol Focus"},{"key":"2024053002462755000_jcp-2023-208973v1.26","doi-asserted-by":"publisher","DOI":"10.1002\/path.4886"},{"key":"2024053002462755000_jcp-2023-208973v1.27","doi-asserted-by":"crossref","first-page":"4011","DOI":"10.1007\/s00345-021-03788-1","article-title":"Prognostic impact of molecular muscle-invasive bladder cancer subtyping approaches and correlations with variant histology in a population-based mono-institutional cystectomy cohort","volume":"39","author":"Weyerer","year":"2021","journal-title":"World J Urol"},{"key":"2024053002462755000_jcp-2023-208973v1.28","doi-asserted-by":"crossref","first-page":"e90","DOI":"10.1016\/j.eururo.2021.12.033","article-title":"Re: Gottfrid Sjodahl, Johan Abrahamsson, Karin Holmsten, et al. different responses to Neoadjuvant chemotherapy in urothelial carcinoma molecular subtypes. Eur Urol. 2022;81:316-7.: Neoadjuvant chemotherapy response in muscle-invasive bladder cancer: differences in intrinsic biology or subtyping nomenclature?","volume":"81","author":"de Jong","year":"2022","journal-title":"Eur Urol"},{"key":"2024053002462755000_jcp-2023-208973v1.29","doi-asserted-by":"crossref","first-page":"4833","DOI":"10.1038\/s41467-021-24837-8","article-title":"Reconciling differences in impact of molecular subtyping on response to cisplatin-based chemotherapy","volume":"12","author":"Roumiguie","year":"2021","journal-title":"Nat Commun"},{"key":"2024053002462755000_jcp-2023-208973v1.30","doi-asserted-by":"crossref","DOI":"10.3390\/cancers14071692","article-title":"Molecular subtypes as a basis for stratified use of neoadjuvant chemotherapy for muscle-invasive bladder cancer-a narrative review","volume":"14","author":"Sj\u00f6dahl","year":"2022","journal-title":"Cancers (Basel)"},{"key":"2024053002462755000_jcp-2023-208973v1.31","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/j.urolonc.2019.04.010","article-title":"Molecular subtypes applied to a population-based modern cystectomy series do not predict cancer-specific survival","volume":"37","author":"Kollberg","year":"2019","journal-title":"Urol Oncol"},{"key":"2024053002462755000_jcp-2023-208973v1.32","doi-asserted-by":"publisher","DOI":"10.1097\/JU.0000000000000351"},{"key":"2024053002462755000_jcp-2023-208973v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2013.67"},{"key":"2024053002462755000_jcp-2023-208973v1.34","doi-asserted-by":"crossref","DOI":"10.1136\/jitc-2019-000162","article-title":"Cytotoxic T-cell-related gene expression signature predicts improved survival in muscle-invasive urothelial bladder cancer patients after radical cystectomy and adjuvant chemotherapy","volume":"8","author":"Eckstein","year":"2020","journal-title":"J Immunother Cancer"},{"key":"2024053002462755000_jcp-2023-208973v1.35","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2014.11.006"},{"key":"2024053002462755000_jcp-2023-208973v1.36","doi-asserted-by":"crossref","first-page":"2126","DOI":"10.1038\/s41467-023-37568-9","article-title":"Expression-based subtypes define pathologic response to neoadjuvant immune-Checkpoint inhibitors in muscle-invasive bladder cancer","volume":"14","author":"Robertson","year":"2023","journal-title":"Nat Commun"},{"key":"2024053002462755000_jcp-2023-208973v1.37","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1016\/j.juro.2017.06.086","article-title":"Prognostic value of PD-1 and PD-L1 expression in patients with high grade upper tract urothelial carcinoma","volume":"198","author":"Krabbe","year":"2017","journal-title":"J Urol"},{"key":"2024053002462755000_jcp-2023-208973v1.38","doi-asserted-by":"crossref","first-page":"6658","DOI":"10.1038\/s41467-022-33980-9","article-title":"Collaborative study from the bladder cancer advocacy network for the Genomic analysis of metastatic urothelial cancer","volume":"13","author":"Damrauer","year":"2022","journal-title":"Nat Commun"},{"key":"2024053002462755000_jcp-2023-208973v1.39","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1111\/bju.15984","article-title":"Prognostic impact of variant histologies in urothelial bladder cancer treated with radical cystectomy","volume":"132","author":"Claps","year":"2023","journal-title":"BJU Int"},{"key":"2024053002462755000_jcp-2023-208973v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2018.09.003"}],"container-title":["Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jcp-2023-208973","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T18:16:37Z","timestamp":1717092997000},"score":1,"resource":{"primary":{"URL":"https:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jcp-2023-208973"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,21]]},"references-count":40,"alternative-id":["10.1136\/jcp-2023-208973"],"URL":"https:\/\/doi.org\/10.1136\/jcp-2023-208973","relation":{},"ISSN":["0021-9746","1472-4146"],"issn-type":[{"type":"print","value":"0021-9746"},{"type":"electronic","value":"1472-4146"}],"subject":[],"published":{"date-parts":[[2023,11,21]]}}}