Abstract
PURPOSEThe 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 METHODSThe 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. RESULTSOverall, 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. CONCLUSIONWe 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.
Highlights
Urothelial carcinoma of the bladder (UCB) is one of the most frequently diagnosed and harmful cancers worldwide [1]
In this systematic review we aimed to summarize the available evidence as well as to determine whether pretreatment tissue-based biomarkers may help predict oncologic and pathologic outcomes in patients treated with neoadjuvant systemic therapy (NAST) for UCB
This review on the impact of using pretreatment tissuebased biomarkers to select patients who are most likely to benefit from NAST generated several important findings
Summary
Urothelial carcinoma of the bladder (UCB) is one of the most frequently diagnosed and harmful cancers worldwide [1]. Neoadjuvant cisplatin based combination chemotherapy (NAC) prior to radical cystectomy is the preferred first treatment in cisplatin eligible patients with muscle-invasive UCB [2, 3]. UCB is a highly heterogeneous disease with varied response rates when therapies are given in unselected patient populations. Modern medical decisions can be tailored to the individual patient based on predicted response or risk of disease. Molecular markers are promising tools that may give insight into which UCB patients will or will not benefit from neoadjuvant systemic therapy (NAST) and which have the potential to overcome the limitations of conventionally used prognostic risk factors. Numerous publications provided data on potential molecular markers associated with NAC response in UCB patients; none is yet validated or widely used in the clinical practice [7−9]
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