Impact of Molecular Subtyping and Immune Infiltration on Pathological Response and Outcome Following Neoadjuvant Pembrolizumab in Muscle-invasive Bladder Cancer

Necchi, Andrea; Raggi, Daniele; Gallina, Andrea; Ross, Jeffrey S.; Farè, Elena; Giannatempo, Patrizia; Marandino, Laura; Colecchia, Maurizio; Lucianò, Roberta; Bianchi, Marco; Colombo, R.; Salonia, Andrea; Gandaglia, Giorgio; Fossati, Nicola; Bandini, Marco; Pederzoli, Filippo; Capitanio, Umberto; Montorsi, Francesco; Jong, Joep J. de; Dittamore, Ryan; Liu, Yang; Davicioni, Elai; Boormans, Joost L.; Briganti, Alberto; Black, Peter C.; Gibb, Ewan A.

doi:10.1016/j.eururo.2020.02.028

Cited by 138 publications

(82 citation statements)

References 24 publications

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“…Specifically, hallmark signatures for IFNg and IFNa responses were associated with pCR after neoadjuvant pembrolizumab. These data emphasize that RNA profiling may be a potential tool for personalizing neoadjuvant therapy selection[28].…”

mentioning

confidence: 72%

Rationale and Outcomes for Neoadjuvant Immunotherapy in Urothelial Carcinoma of the Bladder

Rouanne

Bajorin

Hannan

et al. 2020

European Urology Oncology

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mentioning

confidence: 72%

Rationale and Outcomes for Neoadjuvant Immunotherapy in Urothelial Carcinoma of the Bladder

Rouanne

Bajorin

Hannan

et al. 2020

European Urology Oncology

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“…However, high infiltration of CD8 + T cells has been associated with Claudin-low tumors [62,122] and luminal-infiltrate tumors [62]. Therefore, the authors hypothesize that these patients can benefit from checkpoint inhibitors (Figure 2) [39,40,145]. Interestingly, it was shown that NE-like tumors, given the low TGFβ pathway (low TGFβ1 and TGFβR1), and LumU, given the highest tumor mutation burden and tumor antigen burden, would benefit from ICIs (Figure 2) [146].…”

Section: Molecular Classification To Guide Treatment Choicementioning

confidence: 99%

Evolution of Urothelial Bladder Cancer in the Context of Molecular Classifications

Minoli

Kiener

Thalmann

et al. 2020

IJMS

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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.

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“…Recent technological advances have allowed for efficient deep molecular profiling of bladder cancer tumors to support prediction of clinical outcomes and responses to therapy 17,18,21 . Transcriptomic profiling of biopsy and cystectomy specimens has, for instance, revealed distinct molecular subtypes of bladder cancer 16,18,20,22,23 . Similar to histology, molecular classification reveals important tumor heterogeneity with coexistence of luminal and basal subtypes within the same tumor in ~30% of cases 24,29 .…”

Section: Current Precision Medicine-approaches For the Treatment Of Bmentioning

confidence: 99%

Emerging Roles of Urine-Derived Components for the Management of Bladder Cancer: One Man’s Trash is Another Man’s Treasure

Minkler¹,

Lucien²,

Kimber³

et al. 2020

Preprint

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Urinary bladder cancer (UBC) is the most common malignancy of the urinary tract in humans, with an estimated global prevalence of 1.1 million cases over 5 years1. Due to high rates of recurrence and resistance to chemotherapy, UBC is one of the most expensive cancers to treat, resulting in significant health care costs. There is, therefore, a critical need to develop innovative molecular and cellular tools to refine patient stratification and help predict response to treatment. Urine is an underused resource of biological components shed from bladder tumors, such as exfoliated cells and extracellular vesicles, that could serve as molecular fingerprints and provide valuable biological insights into tumor phenotype and mechanisms of resistance to chemotherapy. Additionally, characterization of urine-derived extracellular vesicles and cells could be used as reliable biomarkers for prediction of response to neoadjuvant therapy.

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Impact of Molecular Subtyping and Immune Infiltration on Pathological Response and Outcome Following Neoadjuvant Pembrolizumab in Muscle-invasive Bladder Cancer

Cited by 138 publications

References 24 publications

Rationale and Outcomes for Neoadjuvant Immunotherapy in Urothelial Carcinoma of the Bladder

Rationale and Outcomes for Neoadjuvant Immunotherapy in Urothelial Carcinoma of the Bladder

Evolution of Urothelial Bladder Cancer in the Context of Molecular Classifications

Emerging Roles of Urine-Derived Components for the Management of Bladder Cancer: One Man’s Trash is Another Man’s Treasure

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