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Characteristics of upper urinary tract urothelial carcinoma in the context of bladder cancer: a narrative review.

ABSTRACT: Urothelial carcinomas (UC) arise from the urothelium that covers the proximal urethra, urinary bladder, and the upper urinary tract. In daily routine and clinical trials UC originating from different locations are often treated and investigated in the same manner. However, differences between the two locations seem to be apparent and may question in handling them as a single oncologic entity. In this review we discuss similarities and differences between bladder and upper urinary tract UC and consider their potential impact on treatment strategies. Despite similarities of UC in the bladder (BC) and the upper urinary tract (UTUC), clinicopathologic and molecular differences may question to generally assemble both as a single tumor entity. Treatment standards for UTUC are often adopted from BC. However, a specific investigation in the former may still be meaningful as shown by the example of adjuvant cisplatin based chemotherapy. In conclusion, future investigations should prioritize the understanding of the tumor biology of both BC and UTUC. This may reveal which UTUC can be treated according to treatment standards of BC and in which cases, a separate approach may be more appropriate.

SUBMITTER: Giudici N

PROVIDER: S-EPMC8575564 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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Characteristics of upper urinary tract urothelial carcinoma in the context of bladder cancer: a narrative review.

Giudici Nicola N Bonne Fieke F Blarer Jennifer J Minoli Martina M Krentel Friedemann F Seiler Roland R

Translational andrology and urology 20211001 10

Urothelial carcinomas (UC) arise from the urothelium that covers the proximal urethra, urinary bladder, and the upper urinary tract. In daily routine and clinical trials UC originating from different locations are often treated and investigated in the same manner. However, differences between the two locations seem to be apparent and may question in handling them as a single oncologic entity. In this review we discuss similarities and differences between bladder and upper urinary tract UC and co ...[more]

PMID: 34804846

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Project description:Background and objectiveAlthough 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.MethodsThis 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.Key content and findingsA clinical trial of nivolumab in an adjuvant setting (CheckMate 274) implied that immune-checkpoint inhibitors might be less efficacious in UTUC than in UBC. Genomic and transcriptomic studies suggest that UTUC has a high frequency of FGFR3 mutations and predominantly shows the luminal papillary subtype, which is immunologically cold with low T-cell infiltration. These findings are consistent with a possible lower response rate to immunotherapy in UTUC than that in UBC. Clinical trials of enfortumab vedotin in a third-line setting (EV201 and EV301) implied that enfortumab vedotin might be less efficacious in UTUC than in UBC. Previous immunohistochemical analyses suggest that UTUC might have a slightly lower rate of Nectin-4 positivity than UBC, indicating that enfortumab vedotin was less efficacious in UTUC than in UBC.ConclusionsClinical differences in the effects of targeted drugs for UTUC and UBC may highlight the molecular differences between these diseases. The treatment strategy should be optimized based on further investigation of the molecular characteristics of UTUC.

Dataset Information

Characteristics of upper urinary tract urothelial carcinoma in the context of bladder cancer: a narrative review.

Publications

Characteristics of upper urinary tract urothelial carcinoma in the context of bladder cancer: a narrative review.

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