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.

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