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Catalog of prognostic tissue-based biomarkers in patients treated with neoadjuvant systemic therapy for urothelial carcinoma of the bladder: a systematic review
E. Laukhtina, B. Pradere, K. Mori, VM. Schuettfort, F. Quhal, H. Mostafaei, R. Sari Motlangh, S. Katayama, NC. Grossmann, M. Moschini, D. Enikeev, SF. Shariat, European Association of Urology—Young Academic Urologists (EAU-YAU): Urothelial...
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, práce podpořená grantem, systematický přehled
- MeSH
- karcinom z přechodných buněk chemie farmakoterapie MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- nádory močového měchýře chemie farmakoterapie MeSH
- neoadjuvantní terapie MeSH
- prognóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- systematický přehled MeSH
PURPOSE: The present systematic review aimed to identify prognostic values of tissue-based biomarkers in patients treated with neoadjuvant systemic therapy (NAST), including chemotherapy (NAC) and checkpoint inhibitors (NAI) for urothelial carcinoma of the bladder (UCB). MATERIAL AND METHODS: The PubMed, Web of Science, and Scopus databases were searched in August 2020 according to the PRISMA statement. Studies were deemed eligible if they compared oncologic or pathologic outcomes in patients treated with NAST for UCB with and without detected pretreatment tissue-based biomarkers. RESULTS: Overall, 44 studies met our eligibility criteria. Twenty-three studies used immunohistochemistry (IHC), 19 - gene expression analysis, three - quantitative polymerase chain reaction (QT PCR), and two - next-generation sequencing (NGS). According to the currently available literature, predictive IHC-assessed biomarkers, such as receptor tyrosine kinases and DNA repair pathway alterations, do not seem to convincingly improve our prediction of pathologic response and oncologic outcomes after NAC. Luminal and basal tumor subtypes based on gene expression analysis showed better NAC response, while claudin-low and luminal-infiltrated tumor subtypes did not. In terms of NAI, PD-L1 seems to maintain value as a predictive biomarker, while the utility of both tumor mutational burden and molecular subtypes remains controversial. Specific genomic alterations in DNA repair genes have been shown to provide significant predictive value in patient treated with NAC. QT PCR quantification of specific genes selected through microarray analysis seems to classify cases regarding their NAC response. CONCLUSION: We believe that the present systematic review may offer a robust framework that will enable the testing and validation of predictive biomarkers in future prospective clinical trials. NGS has expanded the discovery of molecular markers that are reflective of the mechanisms of the NAST response.
Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic
Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria
Department of Urology King Fahad Specialist Hospital Dammam Saudi Arabia
Department of Urology Luzerner Kantonsspital Lucerne Switzerland
Department of Urology The Jikei University School of Medicine Tokyo Japan
Department of Urology University Hospital of Tours Tours France
Department of Urology University Hospital Zurich Zurich Switzerland
Department of Urology University Medical Center Hamburg Eppendorf Hamburg Germany
Department of Urology University of Texas Southwestern Dallas Texas USA
Department of Urology Weill Cornell Medical College New York USA
European Association of Urology Research Foundation Arnhem Netherlands
Institute for Urology and Reproductive Health Sechenov University Moscow Russia
Karl Landsteiner Institute of Urology and Andrology Vienna Austria
Research Center for Evidence Based Medicine Tabriz University of Medical Sciences Tabriz Iran
Citace poskytuje Crossref.org
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- $a Laukhtina, Ekaterina $u Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria; Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia
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- $a PURPOSE: The present systematic review aimed to identify prognostic values of tissue-based biomarkers in patients treated with neoadjuvant systemic therapy (NAST), including chemotherapy (NAC) and checkpoint inhibitors (NAI) for urothelial carcinoma of the bladder (UCB). MATERIAL AND METHODS: The PubMed, Web of Science, and Scopus databases were searched in August 2020 according to the PRISMA statement. Studies were deemed eligible if they compared oncologic or pathologic outcomes in patients treated with NAST for UCB with and without detected pretreatment tissue-based biomarkers. RESULTS: Overall, 44 studies met our eligibility criteria. Twenty-three studies used immunohistochemistry (IHC), 19 - gene expression analysis, three - quantitative polymerase chain reaction (QT PCR), and two - next-generation sequencing (NGS). According to the currently available literature, predictive IHC-assessed biomarkers, such as receptor tyrosine kinases and DNA repair pathway alterations, do not seem to convincingly improve our prediction of pathologic response and oncologic outcomes after NAC. Luminal and basal tumor subtypes based on gene expression analysis showed better NAC response, while claudin-low and luminal-infiltrated tumor subtypes did not. In terms of NAI, PD-L1 seems to maintain value as a predictive biomarker, while the utility of both tumor mutational burden and molecular subtypes remains controversial. Specific genomic alterations in DNA repair genes have been shown to provide significant predictive value in patient treated with NAC. QT PCR quantification of specific genes selected through microarray analysis seems to classify cases regarding their NAC response. CONCLUSION: We believe that the present systematic review may offer a robust framework that will enable the testing and validation of predictive biomarkers in future prospective clinical trials. NGS has expanded the discovery of molecular markers that are reflective of the mechanisms of the NAST response.
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