Identifying Urothelial Cancer Subtypes Matters

Gene expression profiling suggests 3 main subtypes of urothelial cancer: basal, p53-like, and luminal.
Gene expression profiling suggests 3 main subtypes of urothelial cancer: basal, p53-like, and luminal.

ORLANDO, Fla.—Urothelial cancer can no longer be considered a single disease, and genetic subtyping should be considered for all tumors, as this may have implications for therapeutic decision-making, investigators concluded in a presentation at the 2015 Genitourinary Cancers Symposium.

Arlene O. Siefker-Radtke, MD, of the University of Texas MD Anderson Cancer Center in Houston, and colleagues performed gene expression profiling (GEP) on transurethral resection and cystectomy specimens from 39 and 33 bladder cancer patients, respectively, with matched specimens for 23 patients. These patients were among 60 participants enrolled in a neoadjuvant trial of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (DDMVAC) plus bevacizumab.

The investigators noted that GEP suggests 3 main subtypes of urothelial cancer: basal, p53-like, and luminal. Historically, basal has the worse prognosis, with high proliferation and HIF-1 expression.

Results showed that patients with basal tumors had significantly improved 5-year overall survival (OS) compared with those who had luminal and p53-like subtypes (91% vs. 73% and 36%, respectively). The investigators confirmed the survival benefit associated with the basal subtype in a validation cohort of 49 patients treated with perioperative MVAC in a previously published trial. In that trial, the 5-year OS rates in patients with basal, luminal and p53-like tumors were 77%, 57%, and 57%, respectively.

Bone metastases were associated exclusively with the p53-like subtype.

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