scholarly journals The consensus molecular classification of muscle-invasive bladder cancer

2018 ◽  
Author(s):  
Aurélie Kamoun ◽  
Aurélien de Reyniès ◽  
Yves Allory ◽  
Gottfrid Sjödahl ◽  
A. Gordon Robertson ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Stromal Cells ◽  
Molecular Subtypes ◽  
Predictive Biomarkers ◽  
Molecular Classification ◽  
Classification Systems ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

AbstractMuscle-Invasive Bladder Cancer (MIBC) is a molecularly diverse disease with heterogeneous clinical outcomes. Several molecular classifications have been proposed, yielding diverse sets of subtypes, which hampers the clinical implications of such knowledge. Here, we report the results of a large international effort to reach a consensus on MIBC molecular subtypes. Using 1750 MIBC transcriptomes and a network-based analysis of six independent MIBC classification systems, we identified a consensus set of six molecular classes: Luminal Papillary (24%), Luminal Non-Specified (8%), Luminal Unstable (15%), Stroma-rich (15%), Basal/Squamous (35%), and Neuroendocrine-like (3%). These consensus classes differ regarding underlying oncogenic mechanisms, infiltration by immune and stromal cells, and histological and clinical characteristics. This consensus system offers a robust framework that will enable testing and validating predictive biomarkers in future clinical trials.

Re: Aurélie Kamoun, Aurélien de Reyniès, Yves Allory, et al. A Consensus Molecular Classification of Muscle-invasive Bladder Cancer. Eur Urol 2020;77:420–33

2020 ◽  
Vol 77 (4) ◽  
pp. e105-e106
Author(s):  
Stephen B. Williams ◽  
Peter C. Black ◽  
Lars Dyrskjøt ◽  
Roland Seiler ◽  
Bernd Schmitz-Dräger ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Molecular Classification ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

scholarly journals A Consensus Molecular Classification of Muscle-invasive Bladder Cancer

2020 ◽  
Vol 77 (4) ◽  
pp. 420-433 ◽  
Author(s):  
Aurélie Kamoun ◽  
Aurélien de Reyniès ◽  
Yves Allory ◽  
Gottfrid Sjödahl ◽  
A. Gordon Robertson ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Molecular Classification ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

scholarly journals Multi-omics consensus ensemble refines the classification of muscle-invasive bladder cancer with stratified prognosis, tumour microenvironment and distinct sensitivity to frontline therapies

2021 ◽  
Author(s):  
Xiaofan Lu ◽  
Jialin Meng ◽  
Liwen Su ◽  
Liyun Jiang ◽  
Haitao Wang ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
External Validation ◽  
Molecular Classification ◽  
R Package ◽  
Tumour Microenvironment ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Molecular Profiles ◽  
Muscle Invasive

The molecular classification of muscle-invasive bladder cancer (MIBC) based on transcriptomic signatures has been extensively studied. The complementary nature of information provided by different molecular profiles motivated us to refine MIBC classification by aggregating multi-omics data. We generated a consensus ensemble through ten multi-omics integrative clustering approaches on 396 MIBCs from TCGA. A total of 701 MIBCs from different sequencing technologies were used for external validation. Associations between subtypes and prognosis, molecular profiles, the tumour microenvironment, and potential response to frontline therapies were further analyzed. Nearest template prediction and random forest classification were used to develop a predictive signature/classifier for MIBC refinement. We identified four integrative consensus subtypes of MIBC, which were further designated basal-inflamed, basal-noninflamed, luminal-excluded and luminal-desert by immune profiling. Of note, the refinement of basal-like MIBC classification adds to the literature by identifying a basal-noninflamed MIBC subtype presenting with a significantly poor outcome and a global immune-cold phenotype, which might be triggered by Chr4 deletion and high activation of the oncogenic NRF2 pathway. In contrast, basal-inflamed MIBC showed high immunocyte infiltration and high expression of potential targets for immunotherapy. Using an external metastatic MIBC cohort in which patients received anti-PD-L1 treatment, we suggested that basal-inflamed MIBC had a higher likelihood of responding to immunotherapy than other MIBCs. The R package "refineMIBC" was offered as a research tool to refine MIBC from a single-sample perspective (https://github.com/xlucpu/refineMIBC). This consensus ensemble refines the intrinsic MIBC subtypes, which provides a blueprint for the clinical development of rational targeted and immunotherapeutic strategies.

scholarly journals A Consensus Molecular Classification of Muscle-Invasive Bladder Cancer

2019 ◽  
Author(s):  
Aurélie Kamoun ◽  
Aurélien de Reyniès ◽  
Yves Allory ◽  
Gottfrid Sjödahl ◽  
A. Gordon Robertson ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Molecular Classification ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Muscle Invasive

scholarly journals Evolution of Urothelial Bladder Cancer in the Context of Molecular Classifications

2020 ◽  
Vol 21 (16) ◽  
pp. 5670
Author(s):  
Martina Minoli ◽  
Mirjam Kiener ◽  
George N. Thalmann ◽  
Marianna Kruithof-de Julio ◽  
Roland Seiler
Keyword(s):  
Bladder Cancer ◽  
Molecular Subtypes ◽  
Checkpoint Inhibitors ◽  
Classification Systems ◽  
Response To Treatment ◽  
Invasive Bladder Cancer ◽  
Class Iii ◽  
Muscle Invasive Bladder Cancer ◽  
Choice Of Treatment ◽  
Muscle Invasive

Bladder cancer is a heterogeneous disease that is not depicted by current classification systems. It was originally classified into non-muscle invasive and muscle invasive. However, clinically and genetically variable tumors are summarized within both classes. A definition of three groups may better account for the divergence in prognosis and probably also choice of treatment. The first group represents mostly non-invasive tumors that reoccur but do not progress. Contrarily, the second group represent non-muscle invasive tumors that likely progress to the third group, the muscle invasive tumors. High throughput tumor profiling improved our understanding of the biology of bladder cancer. It allows the identification of molecular subtypes, at least three for non-muscle invasive bladder cancer (Class I, Class II and Class III) and six for muscle-invasive bladder cancer (luminal papillary, luminal non-specified, luminal unstable, stroma-rich, basal/squamous and neuroendocrine-like) with distinct clinical and molecular phenotypes. Molecular subtypes can be potentially used to predict the response to treatment (e.g., neoadjuvant chemotherapy and immune checkpoint inhibitors). Moreover, they may allow to characterize the evolution of bladder cancer through different pathways. However, to move towards precision medicine, the understanding of the biological meaning of these molecular subtypes and differences in the composition of cell subpopulations will be mandatory.

scholarly journals Intratumoral heterogeneity of surrogate molecular subtypes in urothelial carcinoma in situ of the urinary bladder: implications for prognostic stratification of high-risk non-muscle-invasive bladder cancer

2021 ◽  
Author(s):  
Stefan Garczyk ◽  
Felix Bischoff ◽  
Ursula Schneider ◽  
Reinhard Golz ◽  
Friedrich-Carl von Rundstedt ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
High Risk ◽  
Carcinoma In Situ ◽  
Molecular Subtypes ◽  
Smoking Status ◽  
Invasive Bladder Cancer ◽  
Muscle Invasive Bladder Cancer ◽  
Prognostic Stratification ◽  
Muscle Invasive

AbstractReliable factors predicting the disease course of non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) are unavailable. Molecular subtypes have potential for prognostic stratification of muscle-invasive bladder cancer, while their value for CIS patients is unknown. Here, the prognostic impact of both clinico-pathological parameters, including CIS focality, and immunohistochemistry-based surrogate subtypes was analyzed in a cohort of high-risk NMIBC patients with CIS. In 128 high-risk NMIBC patients with CIS, luminal (KRT20, GATA3, ERBB2) and basal (KRT5/6, KRT14) surrogate markers as well as p53 were analyzed in 213–231 biopsies. To study inter-lesional heterogeneity of CIS, marker expression in independent CIS biopsies from different bladder localizations was analyzed. Clinico-pathological parameters and surrogate subtypes were correlated with recurrence-free (RFS), progression-free (PFS), cancer-specific (CSS), and overall survival (OS). Forty-six and 30% of CIS patients exhibited a luminal-like (KRT20-positive, KRT5/6-negative) and a null phenotype (KRT20-negative, KRT5/6-negative), respectively. A basal-like subtype (KRT20-negative, KRT5/6-positive) was not observed. A significant degree of inter-lesional CIS heterogeneity was noted, reflected by 23% of patients showing a mixed subtype. Neither CIS surrogate subtype nor CIS focality was associated with patient outcome. Patient age and smoking status were the only potentially independent prognostic factors predicting RFS, PFS, OS, and PFS, respectively. In conclusion, further clarification of heterogeneity of surrogate subtypes in HR NMIBC and their prognostic value is of importance with regard to potential implementation of molecular subtyping into clinical routine. The potential prognostic usefulness of patient age and smoking status for high-risk NMIBC patients with CIS needs further validation.

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