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Review
. 2023 Jan-Dec:22:15330338231159753.
doi: 10.1177/15330338231159753.

Upper Tract Urinary Carcinoma: A Unique Immuno-Molecular Entity and a Clinical Challenge in the Current Therapeutic Scenario

Giulia Mazzaschi  1   2 , Giulia Claire Giudice  1   2 , Matilde Corianò  1   2 , Davide Campobasso  3 , Fabiana Perrone  1 , Michele Maffezzoli  1   2 , Irene Testi  1   2 , Luca Isella  1   2 , Umberto Maestroni  3 , Sebastiano Buti  1   2
Affiliations
Review

Upper Tract Urinary Carcinoma: A Unique Immuno-Molecular Entity and a Clinical Challenge in the Current Therapeutic Scenario

Giulia Mazzaschi et al. Technol Cancer Res Treat. 2023 Jan-Dec.

Abstract

Urothelial carcinoma (UC) is the most frequent malignancy of the urinary tract, which consists of bladder cancer (BC) for 90%, while 5% to 10%, of urinary tract UC (UTUC). BC and UTUC are characterized by distinct phenotypical and genotypical features as well as specific gene- and protein- expression profiles, which result in a diverse natural history of the tumor. With respect to BC, UTUC tends to be diagnosed in a later stage and displays poorer clinical outcome. In the present review, we seek to highlight the individuality of UTUC from a biological, immunological, genetic-molecular, and clinical standpoint, also reporting the most recent evidence on UTUC treatment. In this regard, while the role of surgery in nonmetastatic UTUC is undebated, solid data on adjuvant or neoadjuvant chemotherapy are still an unmet need, not permitting a definite paradigm shift in the standard treatment. In advanced setting, evidence is mainly based on BC literature and retrospective studies and confirms platinum-based combination regimens as bedrock of first-line treatment. Recently, immunotherapy and target therapy are gaining a foothold in the treatment of metastatic disease, with pembrolizumab and atezolizumab showing encouraging results in combination with chemotherapy as a first-line strategy. Moreover, atezolizumab performed well as a maintenance treatment, while pembrolizumab as a single agent achieved promising outcomes in second-line setting. Regarding the target therapy, erdafitinib, a fibroblast growth factor receptor inhibitor, and enfortumab vedotin, an antibody-drug conjugate, proved to have a strong antitumor property, likely due to the distinctive immune-genetic background of UTUC. In this context, great efforts have been addressed to uncover the biological, immunological, and clinical grounds in UTUC patients in order to achieve a personalized treatment.

Keywords: clinical management; genomic profile; immune background; upper tract urinary carcinoma.

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Conflict of interest statement

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Graphical abstract illustrating the main urinary tract urothelial carcinoma (UTUC)-centred fields analyzed in the present review.
Figure 2.
Figure 2.
Graphical representation of UTUC embryogenetic process.
See this image and copyright information in PMC

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