Clinical, genomic characteristics, and Decipher® results

Case characteristicsCase 1Case 2Case 3Case 4
Age/Sex72/Male57/Male80/Female64/Male
Upper tract locationRenal pelvis and ureterRenal pelvis and ureterRenal pelvisRenal pelvis
Initial stageIIIIVIIIIV
Metastatic (Y/N); sitesN; N/AY; lung, bronchusY; RP nodes, liverY; spine osseous
Neoadjuvant chemo (Y/N); cyclesY; 3N; N/AN; N/AN; N/A
Treatment responseResidual ypT3 after NAC but without metastatic diseaseProgressive diseaseProgressive diseaseInitial stable disease then progressive disease
Final clinical stageStage IIIStage IVStage IVStage IV
Final pT stage ypT3pT3cN1cM1pT3cN2MxpT3aNxM1
Variant histologyHG UTUC with glandular and focal squamous differentiationHG UTUC with squamous differentiation of 40%Pure HG UTUCHG UTUC with 30% sarcomatoid features and 20% necrosis
Decipher® subtype probabilityBasal probability 53.4%/Basal Claudin-low 43%Basal probability 80.4%Basal probability 82.4%Basal probability 39.4%/Basal Claudin-low probability 43.5%
Decipher subtypeBasal/Basal Claudin-lowBasalBasalBasal/Basal Claudin-low
Consensus subtypeStroma-richBasal/SquamousBasal/SquamousStroma-rich
UNC subtypeBasalBasalBasalBasal
FGFR3 activity classinactiveinactiveinactiveinactive
Immune190 score0.700.270.680.48
ESTIMATE stromal score3,675–8751,8892,245
Foundation medicine (NGS results)N/APD-L1 TPS 1%; MS-Stable; TMB—6 Muts/Mb; CASP8 loss exons 3-7; CDKN2A loss; CDKN2B loss; HRAS G12S; MTAP loss; TERT promoter -124C>T; VUS: BTK Y418H; CDH1 V794I; CSF1R V48M; HRAS L163fs*52; MITF E207G; NOTCH3 S872F; RBM10 G280V; RPTOR D821N; SNCAIP R269Q; TSC2 R1268HMS-Stable; TMB—11 Muts/Mb; AKT2 amplification; CDKN2A loss; CDKN2B loss; ERBB3 E332K; KDM6A Q670*; MTAP loss; RAF1 amplification; TERT promoter -124C>T; TP53 lossN/A
Overall survival36.6 mos8.7 mos10.8 mos14.2 mos
Progression free survivalN/A6 mos0.7 mos2.5 mos
Decipher gene outlier categoryImmune activation/angiogenesisFGF/ADCImmune activation/angiogenesisImmune activation

HG UTUC: high-grade upper tract urothelial carcinoma; mos: months; N/A: not applicable; NAC: neoadjuvant chemotherapy; RP: retroperitoneal; TPS: tumor proportion score; VUS: variants of unknown significance; UNC: University of North Carolina; NGS: next generation sequencing; PD-L1: programmed death ligand 1; TMB: tumor mutational burden; FGFR: fibroblast growth factor receptor