Gibb, Ewan A.

831 Background: Long non-coding RNA (lncRNA)-based genomic profiling has suggested utility to identify a distinct tumor subgroup corresponding to a favorable prognosis in patients with bladder cancer. Here, we further evaluate a genomic classifier in a cohort of patients undergoing radical cystectomy (RC). Methods: Transcriptome-wide expression profiling using Decipher Bladder was performed on TURBT samples from a cohort of patients with high grade, clinically organ confined (cTa-T2N0M0) UC who subsequently underwent RC without any neoadjuvant therapy (n=226). LncRNA-based luminal favorable status was determined using a previously developed genomic classifier. The primary endpoint was overall survival (OS) following surgery. Secondary endpoints included cancer-specific mortality and upstaging at RC. Results: In the study, 134 patients were clinical NMIBC (cTa/Tis/T1) and 92 patients were cT2. We identified 60 patients with luminal favorable subtype, all of which showed robust gene expression patterns associated with less aggressive bladder cancer biology. On MVA, patients with the luminal favorable subtype (vs. without) were significantly associated with lower odds of upstaging to pT3+ disease (OR [95% CI] 0.32 [0.12-0.82], p = 0.02), any upstaging (OR [95% CI] 0.41 [0.20-0.83], p = 0.01), and any upstaging and/or pN+ (OR [95% CI] 0.50 [0.25-1.00], p = 0.05). Luminal favorable bladder cancer was significantly associated with better OS (HR 0.33 [95% CI 0.15-0.74], p=0.007). Conclusions: This study validates the performance of the genomic classifier for identifying urothelial carcinomas with a luminal favorable subtype, harboring less aggressive tumor biology.

Objective To further evaluate a genomic classifier (GC) in a cohort of patients undergoing radical cystectomy (RC), as long non‐coding RNA (lncRNA)‐based genomic profiling has suggested utility in identifying a distinct tumour subgroup corresponding to a favourable prognosis in patients with bladder cancer. Patients and Methods Transcriptome‐wide expression profiling using Decipher Bladder was performed on transurethral resection of bladder tumour samples from a cohort of patients with high‐grade, clinically organ‐confined (cTa–T2N0M0) urothelial carcinoma (UC) who subsequently underwent RC without any neoadjuvant therapy ( n = 226). The lncRNA‐based luminal favourable status was determined using a previously developed GC. The primary endpoint was overall survival (OS) after RC. Secondary endpoints included cancer‐specific mortality and upstaging at RC. Results In the study, 134 patients were clinical non‐muscle‐invasive bladder cancer (cTa/Tis/T1) and 92 patients were cT2. We identified 60 patients with luminal favourable subtype, all of which showed robust gene expression patterns associated with less aggressive bladder cancer biology. On multivariate analysis, patients with the luminal favourable subtype (vs without) were significantly associated with lower odds of upstaging to pathological (p)T3+ disease (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.12–0.82; P = 0.02), any upstaging (OR 0.41, 95% CI 0.20–0.83; P = 0.01), and any upstaging and/or pN+ (OR 0.50, 95% CI 0.25–1.00; P = 0.05). Luminal favourable bladder cancer was significantly associated with better OS (hazard ratio 0.33, 95% CI 0.15–0.74; P = 0.007). Conclusions This study validates the performance of the GC for identifying UCs with a luminal favourable subtype, harbouring less aggressive tumour biology.