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IBCN 2023: Urinary Comprehensive Genomic Profiling Predicts Urothelial Cancer Up To 12 Years Ahead Of Clinical Diagnosis: An Expanded Analysis Of The Golestan Cohort Study

(UroToday.com) Detecting pre-clinical urothelial carcinoma (UC) using urinary comprehensive genomic profiling (uCGP) may providea valuable opportunity for early detection and screening of high-risk populations. The UroAmp (Convergent Genomics) uCGP test uses next-generation sequencing to identify mutations across 60 genes. The authors performed an informatically narrowing of the data to consider 10 genes with the highest performance and test the potential of modified uCGP to detect preclinical urothelial carcinoma.

A urothelial carcinoma screening model was developed using uCGP data from a training cohort consisting of 140 urology controls and96 tumors (56 de novo, 40 recurrent). Model validation was performed in two studies: first a multi-institutionalcase-control design with 96 controls and 70 urothelial carcinoma cases (22 de novo, 48 surveillance); a second using a nested casecontroldesign within the population-based prospective Golestan Cohort Study (50,045 participants), which consisted of 29 asymptomatic individuals who subsequently developed primary urothelial carcinoma (median time to urothelial carcinoma 7.3 years) and 98 matched controls (median f/u 6.1 years).

The urothelial carcinoma screening model was trained to a sensitivity of 88% (97% sensitivity for High-Grade (HG)) and specificity of 94%. In the first validation, a sensitivity of 86% in de novo (87% for HG), 71% overall, and specificity 94% was observed. In the Golestan cohort, baseline uCGP had a prediction sensitivity of 66% (71% for HG) and a specificity of 94%. In contrast baseline TERT predicted 48% of cancers with a specificity of 100%. Cancer-free survival was significantly worse in uGCP-predicted positives vs. negatives (HR 8.5, 95% CI 3.8 – 18.4, p<0.0001). When limited to urothelial carcinoma diagnosis within seven years, UroAmp detected pre-clinical urothelial carcinoma in 86% of future cancers, compared to a sensitivity of 57% using TERT mutations alone.

These results provide the first evidence from a population-based prospective cohort study of potential pre-clinical urothelial carcinoma detection with urinary comprehensive genomic profiling. Moreover, these findings suggest the application of precision based medicine applications in bladder cancer.

Presented by: Florence Le Calvez-Kelm, PhD, International Agency for Research on Cancer, Genomic Epidemiology, Lyon, France

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