Comparison of molecular profiles of upper tract urothelial carcinoma vs. urinary bladder cancer in the era of targeted therapy: a narrative review

Abstract

Background and Objective: Although upper tract urothelial carcinoma (UTUC) shares the histological appearance of urinary bladder cancer (UBC), molecular studies suggest that UTUC and UBC represent two distinct disease entities. However, treatment approaches for UTUC are virtually extrapolated from the evidence on UBC. As targeted drugs-immune-checkpoint inhibitors, fibroblast growth factor receptor inhibitors, and antibody-drug conjugates-target specific molecules, gaining more knowledge about the target-molecular profiles of each drug can help formulate optimal treatment strategies for UTUC.Methods: This narrative review summarized the subgroup analyses of clinical trials of FDA-approved targeted drugs to explore the differential effects of each targeted drug when administered for UTUC compared to UBC. We focused on the differences in mutation frequency, RNA expression subtype, and therapeutic target protein expressions (specifically PD-L1, Nectin-4, and Trop-2) between UTUC and UBC and discussed their relationship with the efficacy of each targeted drug.

Immune checkpoint inhibitors in high‐grade upper tract urothelial carcinoma: Paradigm shift emphasizing organ preservation

“…These observations collectively imply that UTUC may exhibit a reduced response to immunotherapy when compared to bladder carcinoma. 18 The present study results showed significantly improved survival outcomes in group 2, which can now serve as an evidence of the effectiveness of ICIs in high-grade UTUC.…”

“…Additionally, UTUC tends to exhibit the luminal papillary subtype, characterised by a relatively lower presence of immune cells, particularly T cells. These observations collectively imply that UTUC may exhibit a reduced response to immunotherapy when compared to bladder carcinoma 18 . The present study results showed significantly improved survival outcomes in group 2, which can now serve as an evidence of the effectiveness of ICIs in high‐grade UTUC.…”

VCAN Hypomethylation and Expression as Predictive Biomarkers of Drug Sensitivity in Upper Urinary Tract Urothelial Carcinoma

“…According to the findings of Tomiyama et al, the mutation rates of TP53 and ERBB2 were positively correlated with high-grade UTUC patients [ 55 ]. Our heatmap analysis revealed a correlation between the expression of VCAN and the cell migration genes MMP9, TWIST1 and N-cadherin in UTUC patients ( Figure 6 ).…”

PET Imaging in Bladder Cancer: An Update and Future Direction

“…Several targeted therapies and antibody-drug conjugates are currently being used or developed for the treatment of BC. Nectin-4, the target of enfortumab-vedotin, is overexpressed in 83% of bladder UC [67], with lower expression correlating with lower treatment efficacy. Although nectin-4 is not specific for BC, radiolabelled enfortumab may be of interest for predicting treatment response and BC staging.…”