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Review
. 2020 Oct;9(10):6609-6623.
doi: 10.21037/tcr-20-1243.

The therapeutic and prognostic implications of molecular biomarkers in urothelial carcinoma

Ho Won Kang  1   2 , Wun-Jae Kim  1   2 , Seok Joong Yun  1   2
Affiliations
Review

The therapeutic and prognostic implications of molecular biomarkers in urothelial carcinoma

Ho Won Kang et al. Transl Cancer Res. 2020 Oct.

Abstract

Urothelial cell carcinoma (UCC) of the bladder and upper urinary tract is a heterogeneous disease with distinct biologic features resulting in different clinical behaviors. Bladder cancer (BC) is classified into non-muscle invasive BC (NMIBC) and muscle invasive BC (MIBC). NMIBC is associated with high recurrence rates and risk of progression to invasive disease, whereas MIBC is complicated by systemic recurrence after radical cystectomy because of the limited efficacy of available therapies. UCC of the upper urinary tract (UUT-UCC) is a rare but aggressive urologic cancer characterized by multifocality, local recurrence, and metastasis. Conventional histopathologic evaluation of UCC, including tumor stage and grade, cannot accurately predict the behavior of BC and UUT-UCC. Recent clinical and preclinical studies aimed at understanding the molecular landscape of UCC have provided insight into molecular subtyping, inter- or intratumoral heterogeneity, and potential therapeutic targets. Combined analysis of molecular markers and standard pathological features may improve risk stratification and help monitor tumor progression and treatment response, ultimately improving patient outcomes. This review discusses prognostic and therapeutic biomarkers for BC and UUT-UCC, and describes recent advances in molecular stratification that may guide prognosis, patient stratification, and treatment selection.

Keywords: Urothelial cell carcinoma (UCC); biomarkers; liquid biopsy; prognosis; tumor heterogeneity.

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Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tcr-20-1243). The series “Urothelial Carcinoma” was commissioned by the editorial office without any funding or sponsorship. The authors have no other conflicts of interest to declare.

Figures

Figure 1
Figure 1
Schematic illustration of the molecular classification of NMIBC based on gene expression profiling. NMIBC, non-muscle invasive bladder cancer.
Figure 2
Figure 2
Schematic illustration of the molecular classification of MIBC based on gene expression profiling. UNC, University of North Carolina; MDA, MD Anderson Cancer Center; TCGA, The Cancer Genome Atlas; LP, luminal-papillary; LI, luminal-infiltrated; GU, genomically unstable; SCC, squamous cell carcinoma; Mes, mesenchymal; Sc/NE, small cell/neuroendocrine; NAC, neoadjuvant chemotherapy; ICI, immune checkpoint inhibitor; MIBC, muscle invasive bladder cancer.
Figure 3
Figure 3
Integral model of clinico-pathological and molecular analysis for precision medicine in patients with UCC. Combined analysis of molecular markers and standard pathological features may improve risk stratification and help monitor tumor progression and treatment response, ultimately improving patient outcomes in patients with UCC. UCC, urothelial cell carcinoma.
Figure 4
Figure 4
Tumor heterogeneity and therapeutic resistance. Cancer is not a fixed state; rather, it should be considered as a dynamic ecosystem that evolves as the tumor progresses and is modulated strongly by therapeutic pressure.
See this image and copyright information in PMC

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