Validation of a neuroendocrine-like classifier confirms poor outcomes in patients with bladder cancer treated with cisplatin-based neoadjuvant chemotherapy

Grivas, Petros; Bismar, Tarek A.; Alva, A.; Huang, Huei Chung; Liu, Yang; Seiler, Roland; Alimohamed, Nimira; Cheng, Liang; Hyndman, M. Eric; Dabbas, Bashar; Black, Peter C.; Davicioni, Elai; Wright, Jonathan L.; Ornstein, Moshe Chaim; Mian, Omar Y.; Kaimakliotis, Hristos Z.; Gibb, Ewan A.; Lotan, Yair

doi:10.1016/j.urolonc.2019.11.004

Cited by 21 publications

(17 citation statements)

References 19 publications

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“…36 We explored the genomic profile of eight tumors for which adequate tissue was available. As observed in other neuroendocrine cohorts, 4,29 TP53 and RB1 were co-altered in all four NE histology tumors, but other neuronal genes previously described in neuroendocrine-like bladder tumors 37,38 were not present. Additionally, a KRAS activating mutation was seen in one urachal ADC and a SMAD4 truncating mutation in a second, both of which have been reported in cohorts of urinary tract ADC.…”

Section: Discussionsupporting

confidence: 76%

A phase II trial of durvalumab and tremelimumab in metastatic, non‐urothelial carcinoma of the urinary tract

et al. 2020

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Section: Discussionsupporting

confidence: 76%

A phase II trial of durvalumab and tremelimumab in metastatic, non‐urothelial carcinoma of the urinary tract

et al. 2020

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“…The neuroendocrinelike cases showed poor overall survival, consistent with the aggressive behavior of neuroendocrine carcinoma [80]. Validation of this neuroendocrine classifier in a subsequent study supported its ability to identify neuroendocrine-like tumors, with the need to manage these tumors similar to morphologically apparent neuroendocrine carcinomas [81].…”

Section: Neuroendocrine Carcinomamentioning

confidence: 61%

Histologic Variants of Urothelial Carcinoma: Morphology, Molecular Features and Clinical Implications

Alderson

Grivas

Milowsky

et al. 2020

BLC

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Bladder cancer is a heterogeneous disease including conventional urothelial carcinoma (UC) and its histologic variants, and non-urothelial carcinoma, including squamous and glandular neoplasms. Urothelial carcinoma accounts for the majority of bladder cancer cases, but morphologic variants are common and include nested, microcystic, micropapillary, lymphoepithelioma-like, plasmacytoid, sarcomatoid, giant cell, undifferentiated, clear cell and lipoid. Certain variants of UC tend to be associated with a poor prognosis and have diagnostic and potential treatment implications that make the identification of variant histology crucial to clinical decision making. While there is still uncertainty regarding the prognostic implications of many of these variants, identifying and reporting variant histology is important to develop our understanding of their biology. Unique molecular features accompany many of these morphologic variants and to better understand these tumors, we review the molecular and clinical implications of histologic variants of bladder cancer. Major efforts are underway to include variant histology and divergent differentiation of UC in clinical trials to develop evidence based approaches to treatment. The purpose of this article is to review the current literature on variant histology of urothelial cancer and to highlight molecular findings and the clinical relevance of these tumors.

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“…[14][15][16][19][20][21]81,82 The neuroendocrine subtype, which has the worst prognosis of all subtypes, also responds to platinum based chemotherapies. 20,21,83 Hence, patients with squamous or neuroendocrine subtypes are selected to receive NAC, instead of prompt radical cystectomy. FGFR3 mutation in UCs is a representative genetic abnormality categorised as luminal papillary type.…”

Section: Advantage Of Molecular Subtypingmentioning

confidence: 99%

Urothelial carcinoma: variant histology, molecular subtyping, and immunophenotyping significant for treatment outcomes

2021

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Validation of a neuroendocrine-like classifier confirms poor outcomes in patients with bladder cancer treated with cisplatin-based neoadjuvant chemotherapy

Cited by 21 publications

References 19 publications

A phase II trial of durvalumab and tremelimumab in metastatic, non‐urothelial carcinoma of the urinary tract

A phase II trial of durvalumab and tremelimumab in metastatic, non‐urothelial carcinoma of the urinary tract

Histologic Variants of Urothelial Carcinoma: Morphology, Molecular Features and Clinical Implications

Urothelial carcinoma: variant histology, molecular subtyping, and immunophenotyping significant for treatment outcomes

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