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, Aijai S; 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 C; Mian, Omar Y; Kaimakliotis, Hristos Z; Gibb, Ewan A; Lotan, Yair (2020). Validation of a neuroendocrine-like classifier confirms poor outcomes in patients with bladder cancer treated with cisplatin-based neoadjuvant chemotherapy. Urologic oncology, 38(4), pp. 262-268. Elsevier 10.1016/j.urolonc.2019.11.004

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PURPOSE

Neuroendocrine (NE)-like carcinoma is a newly recognized molecular subtype of conventional urothelial carcinoma of the bladder with transcriptomic profiles and clinical outcomes highly similar to histological NE carcinoma. The identification of NE-like tumors is challenging, as these tumors often appear histologically like urothelial carcinoma and can be missed by routine morphological criteria. We previously developed a single-sample classifier to identify NE-like tumors, which we aimed to validate in an independent cohort.

MATERIALS AND METHODS

A single-sample genomic classifier was performed on transurethral specimens from a retrospective multicenter cohort of 234 patients who underwent cisplatin-based neoadjuvant chemotherapy and subsequent radical cystectomy. Outcomes were compared for NE-like vs. non-NE-like.

RESULTS

We identified 10 patients with urothelial tumors of the NE-like subtype, all of which had robust gene expression of neuronal markers, but did not express markers associated with basal or luminal tumors. The cancer-specific mortality rates were significantly higher compared to non-NE-like tumors (P < 0.001), with 5 of the 10 patients dying within 12 months from surgery.

CONCLUSIONS

The single-sample classifier was able to identify urothelial carcinomas with NE-like subtype. These NE-like tumors have demonstrated transcriptomic profiles and clinical behavior similar to histological NE tumors across multiple patient cohorts. We propose that NE-like tumors should be managed similarly to histological NE tumors, and that standard treatments for small cell lung cancer as well as novel strategies may be evaluated in these patients.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology

UniBE Contributor:

Seiler-Blarer, Roland

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1873-2496

Publisher:

Elsevier

Language:

English

Submitter:

Jeannine Wiemann

Date Deposited:

16 Mar 2020 09:45

Last Modified:

04 Aug 2020 09:19

Publisher DOI:

10.1016/j.urolonc.2019.11.004

PubMed ID:

31812633

Uncontrolled Keywords:

Bladder cancer Gene expression analysis Molecular subtypes Neuroendocrine Urothelial carcinoma

BORIS DOI:

10.7892/boris.141111

URI:

https://boris.unibe.ch/id/eprint/141111

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