Catalog of prognostic tissue-based biomarkers in patients treated with neoadjuvant systemic therapy for urothelial carcinoma of the bladder: a systematic review

TY - JOUR

T1 - Catalog of prognostic tissue-based biomarkers in patients treated with neoadjuvant systemic therapy for urothelial carcinoma of the bladder: a systematic review

AU - Laukhtina, Ekaterina

AU - Pradere, Benjamin

AU - Mori, Keiichiro

AU - Schuettfort, Victor M

AU - Quhal, Fahad

AU - Mostafaei, Hadi

AU - Sari Motlangh, Reza

AU - Katayama, Satoshi

AU - Grossmann, Nico C

AU - Moschini, Marco

AU - Enikeev, Dmitry

AU - Shariat, Shahrokh F

N1 - Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

PY - 2021/3

Y1 - 2021/3

N2 - 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.

AB - 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.

KW - Biomarkers, Tumor/analysis

KW - Carcinoma, Transitional Cell/chemistry

KW - Humans

KW - Neoadjuvant Therapy

KW - Prognosis

KW - Urinary Bladder Neoplasms/chemistry

U2 - 10.1016/j.urolonc.2020.12.019

DO - 10.1016/j.urolonc.2020.12.019

M3 - SCORING: Review article

C2 - 33423937

VL - 39

SP - 180

EP - 190

JO - UROL ONCOL-SEMIN ORI

JF - UROL ONCOL-SEMIN ORI

SN - 1078-1439

IS - 3

ER -