787P Urachal (URAC) and non-urachal (NURAC) adenocarcinomas of the urinary bladder: A comparative comprehensive genomic profiling (CGP) study

Although both URAC and NURAC are adenocarcinomas, their sites of origin and etiology are unique. We queried whether their genomic alteration (GA) signatures would also reflect their differences. From a series of 4,863 FFPE tissues from clinically advanced bladder tumors, 85 cases of URAC and 143 cases of NURAC underwent hybrid-capture based CGP to evaluate all classes of GA. Tumor mutational burden (TMB) was determined on 1.1 Mbp of sequenced DNA and microsatellite instability (MSI) was determined on 114 loci. There were significantly more women with NURAC and more men with URAC (p=0.028). Median ages and age ranges were similar. On CGP, the GA/tumor were similar as were GA in major currently untargetable genes including TP53 and KRAS. GA in SMAD4 and MYC were more common in URAC and GA in TERT, ARID1A and APC were more frequent in NURAC than URAC. Male patients had more frequent GA in SMAD4 and APC and females had more GA in KRAS. The major currently targetable GA in both tumor types included PIK3CA (10% in NURAC and 5% in URAC) and ERBB2 (8% in NURAC and 6% in URAC). Biomarkers indicating potential benefit from immunotherapy (IO) were infrequent in both tumor types which generally were MSI stable, featured a low TMB and did not frequently stain for PD-L1 expression even at a low cut-off of ≥ 1%.Table 787PNURACURACNumber of Cases14385Males/Females57/8647/38Median age (range) in years58 (24-83)57 (23-82)GA/tumor5.45.1Selected Top Untargetable GA TP53 KRAS SMAD4 MYC TERT ARID1A APC79% 30% 14% 13% 12% 10% 8%85% 32% 21% 18% 1% 6% 0%Top Targetable GA PIK3CA ERBB2 PTEN MET EGFR10% 8% 4% 4% 4%5% 6% 4% 1% 2%MSI-High2/106 (2%)0/77 (0%)Mean TMB (mut/Mb)2.43.9Median TMB (mut/Mb)3.62.6TMB>10 mut/Mb14 (10%)4 (4%)TMB>20 mut/Mb4 (3%)1 (1%)PD-L1 IHC ≥1% Positive2/11 (18%)1/18 (6%) Open table in a new tab URAC and NRAC have similar GA/tumor and absence of biomarkers predictive of IO response. However, gender frequencies differ as do GA in genes associated with their histogenesis such as TERT and APC. Significant potential treatments for both URAC and NURAC targeting PIK3CA and ERBB2 indicate that CGP has potential to personalize the care of patients suffering from these rare forms of bladder cancer.