A far more detailed understanding of advanced urothelial carcinoma (UC) has resulted in the identification of distinct molecular subtypes. Understanding the molecular subtypes of UC can help to identify distinct patient populations and improve treatment decision-making.
Listen to Dr. Ignacio Durán, Medical Oncologist at Hospital Universitario Marqués de Valdecilla in Santander, talking about why he believes we are moving towards a biomarker-led approach to care in advanced UC.
Find out what the consensus classification of muscle invasive bladder cancer subtypes could mean for how we view advanced UC and what it means for the role of molecular pathology.
A bladder cancer patient’s chance of survival is highly stage dependent and progression from muscle invasive bladder cancer (MIBC) to metastasis is common:
Treatment options for patients that develop metastases currently include chemotherapy or programmed death protein/ligand 1 inhibitors:
Molecular biomarkers have not been commonly used in routine clinical practice in advanced UC.
Evidence is limited and/or conflicting in some areas of advanced and variant bladder cancer management, and the optimal approach remains controversial, warranting further discussion and clarification.
The molecular biomarkers and pathways involved in UC are key to understanding its biological heterogeneity and identifying specific subtypes that may be used to predict clinical outcomes and treatment responsiveness[^2]
The molecular understanding of MIBC has led to a consensus classification of tumour classes with distinct oncogenic mechanisms
Figure 1. Six-class molecular classification system of MIBC
Adapted from Kamoun A et al. 2020.
Figure legend can be found in footnotes at the bottom of the page.
In other cancer types, improved understanding of molecular pathology has enabled biomarker-led precision medicine that can improve outcomes for appropriately selected subsets of patients
The identification of targets in tumours such as colorectal, breast, ovarian and non-small cell lung cancer has led to the development of targeted therapies
Targeting tumours with inhibitors that block aberrant signalling has improved patient outcomes across different cancers, providing efficacy and toxicity benefits
Learn more about FGFR alterations and the value of genetic testing:
Figure 1 Legend
APOBEC=apolipoprotein B mRNA editing catalytic polypeptide-like; CD8 T cells=cytotoxic T lymphocytes; CDKN2A=cyclin-dependent kinase inhibitor 2A; E2F3=gene encoding E2F transcription factor 3; EGFR=epidermal growth factor receptor; ELF3=gene encoding E74 like ETS transcription factor 3; ERBB2=gene encoding receptor tyrosine-protein kinase erbB-2; ERCC2=gene encoding XPD protein; FGFR=fibroblast growth factor receptor; KDM6A=gene encoding lysine-specific demethylase 6A; NK cells=natural killer cells; PPARG=peroxisome proliferator-activated receptor gamma; RB1=gene encoding pRB tumour suppressor; STAG2=gene encoding cohesin subunit SA-2; T2=tumour growth into muscle; T3=tumour growth into fat layer; T4=tumour growth outside of the bladder; TMB=tumour mutational burden; TP53=gene encodes p53.
Figure 2 Legend
Cancers included urothelial carcinomas (transitional cell carcinomas) of the bladder, renal pelvis, ureter, and not specified. The majority of aberrations were activating mutations in FGFR3, including S249C (8 instances), R248C (6 instances), Y373C (2 instances), G370C (2 instances), and K650M (1 instance). Three of these FGFR3 mutations are also about to transform cells in vitro (S249C, S248C, Y737C). Frequencies are expressed as percentages of all 126 cases. There were 44 aberrations in 40 cases (4 cases had more than one aberration), so the total is greater than 100%.