Urine samples from 134 patients with BU NMIBC were collected at baseline and after four cycles of treatment. uCGP was completed using UroAmp (Convergent Genomics). Recurrence risk was calculated at baseline, and molecular response was classified based on change in molecular residual disease (MRD) between the two time points. Comparison of mutations was made to a non-study cohort of high-grade BCG-naïve (BN) NMIBC (n=101). Clinical variables were not available for analysis.
Baseline samples demonstrated high genomic diversity. The number of mutations ranged from 0–20, with a median of 4. Among samples with mutations, allele frequencies ranged from < 1% up to 80%. Copy number gains up to 22x were observed. The most frequently mutated genes in baseline samples included TERT promoter (43%), TP53 (32%), ARID1A (21%), KMT2D (21%), and ERBB2 (15%). NIT1 and SOX4 were frequently amplified (12% and 10%). Compared to BN, BU patients were enriched in: SNVs in ERBB3 (OR=4.6, p=0.01), ERBB2 (OR=2.3, p=0.09), ARID1A (OR=2.2, p=0.05), TP53 (OR=1.9, p=0.05), and TERT promoter (OR=1.8, p=0.05); gain in NIT1 (OR=3.2, p=0.05); and high aneuploidy (OR=3.2, p=0.01). At baseline, 68% of patients were predicted to be at high risk of clinical recurrence. After treatment, 8% showed complete MRD response, 14% partial response, 25% stable MRD, and 46% exhibited MRD expansion.
In conclusion, this study suggests uCGP can identify genomic patterns associated with BU NMIBC and assess response to treatment via MRD measurements. Ongoing correlation with clinical characteristics and outcomes will test the utility of uCGP to monitor therapeutic response.
Presented by: Marie-Pier St-Laurent, University of British Columbia, Vancouver, BC, Canada
Written by: Stephen B. Williams, MD, MBA, MS @SWilliams_MD on Twitter during the International Bladder Cancer Network (IBCN) Annual Meeting, September 29-30, 2023, Montreal, Canada