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.
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.
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.
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.
Urologic oncology. 2019 Dec 04 [Epub ahead of print]
Petros Grivas, Tarek A Bismar, Aijai S Alva, Huei-Chung Huang, Yang Liu, Roland Seiler, Nimira Alimohamed, Liang Cheng, M Eric Hyndman, Bashar Dabbas, Peter C Black, Elai Davicioni, Jonathan L Wright, Moshe C Ornstein, Omar Y Mian, Hristos Z Kaimakliotis, Ewan A Gibb, Yair Lotan
Division of Oncology, Department of Medicine, University of Washington School of Medicine, Fred Hutchinson Cancer Research Center, Seattle, WA., Department of Pathology and Laboratory Medicine, University of Calgary, Cumming School of Medicine, Calgary, AB, Canada., Department of Internal Medicine, University of Michigan, Ann Arbor, MI., Decipher Biosciences, Inc., Vancouver, Canada., Department of Urology, University of Bern, Bern, Switzerland., Department of Medical Oncology, Tom Baker Cancer Center, University of Calgary, Calgary, AB, Canada., Department of Pathology, Indiana University, Indianapolis, IN., Department of Urology, University of Calgary, Cumming School of Medicine, Calgary, AB, Canada., Department of Urologic Sciences, University of British Columbia, Vancouver, BC, Canada., Department of Urology, University of Washington School of Medicine, Fred Hutchinson Cancer Research Center, Seattle, WA., Department of Translational Hematology and Oncology Research, Cleveland Clinic, Cleveland, OH., Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH., Department of Urology, Indiana University, Indianapolis, IN., Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address: .