Comprehensive Genomic Profiling of Upper-tract and Bladder Urothelial Carcinoma

• Published in: European urology focus 2021-11, Vol.7 (6), p.1339-1346
• Main Authors: Necchi, Andrea, Madison, Russell, Pal, Sumanta K., Ross, Jeffrey S., Agarwal, Neeraj, Sonpavde, Guru, Joshi, Monika, Yin, Ming, Miller, Vincent A., Grivas, Petros, Chung, Jon H., Ali, Siraj M.
• Format: Article
• Language: English
• Subjects: Biomarkers, Tumor - genetics; Bladder cancer; Carcinoma, Transitional Cell - genetics; Comprehensive genomic profiling; Genomic alterations; Humans; Kidney Neoplasms - therapy; Proto-Oncogene Proteins B-raf; Upper tract urothelial carcinoma; Ureteral Neoplasms - genetics; Urinary Bladder - pathology; Urinary Bladder Neoplasms - pathology; Urothelial cancer
• ISSN: 2405-4569; 2405-4569
• DOI: 10.1016/j.euf.2020.08.001

Characterization of the different genomic alterations (GAs) in urothelial carcinoma (UC), by site of origin, may identify contrasting therapeutic opportunities and inform distinct putative pathogenetic mechanisms. To describe the genomic landscape of UC based on the anatomic site of the primary tumor. In total, 479 upper tract UC (UTUC) and 1984 bladder UC (BUC) patients underwent comprehensive genomic profiling (CGP) to evaluate all classes of GAs, tumor mutational burden (TMB), and microsatellite instability (MSI) status. Targetable GAs and signatures were assessed according to the European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets (ESCAT). Hybrid-capture–based CGP. Descriptive analyses and differences between anatomic subgroups were reported. In total, 39% of patients with UC harbored one or more tier 1–2 GAs, suggesting potential benefit from approved or investigational therapies. UTUC cases were enriched in FGFR3 short variant (SV) GA (20% vs 13%) and HRAS SV GA (7.3% vs 3%), the latter attributed specifically to enrichment in renal pelvis UC (9.5%) versus ureteral UC (1.8%, p=0.002). RB1 GAs were more frequent in BUC than in UTUC (21% vs 7.8% p