92P - Transformative diagnostics in urothelial carcinoma: Utilizing targeted NGS and LP-WGS for non-invasive detection and personalized medicine

Background

Urothelial carcinoma (UC), the most common urinary system cancer, affects the bladder, upper urinary tract, and renal pelvis. Traditional diagnostics like urinary pathology, cystoscopy, and ureteroscopy are limited by sensitivity and patient compliance issues, highlighting the need for accurate, non-invasive diagnostics. This study examines the use of Next-Generation Sequencing (NGS) for urinary tumor DNA (utDNA) analysis, showcasing its potential as a diagnostic tool for UC.

Methods

This ongoing clinical trial is enrolling 250 patients with symptoms indicative of UC. So far, 20 patients have provided 40 ml urine samples for centralized analysis using two liquid biopsy assays: PredicineCARE (targeted NGS) and PredicineSCORE (low-pass WGS). These assays detect genomic alterations in utDNA, aiming to identify tumor fractions in urine. Their diagnostic efficacy is being evaluated against imaging, cystoscopy, ureteroscopy, and urinary pathology.

Results

In the 20 patients assessed, UC was confirmed in 11, 7 tested negative, and 2 cases remained uncertain. utDNA testing detected tumor fractions in all confirmed and uncertain UC cases, achieving 100% sensitivity and 71.4% specificity. Genomic profiling found 260 mutations and 24 copy number variants, with significant alterations in genes like TP53 and FGFR2/3, pointing to potential FGFR inhibitor treatments. The median urinary copy number burden (uCNB) score, derived from LP-WGS, distinguished between UC-positive and UC-negative patients with significant differences (median score of 9.04 in UC-positive vs. 5.97 in UC-negative, p=0.004). A uCNB threshold of 7.58 accurately identified 8 UC patients with 100% specificity and 73% sensitivity. Clinically UC-negative patients had negative uCNB scores, while one uncertain case tested positive, validating utDNA results and underscoring uCNB's value as a confirmatory biomarker.

Conclusions

The utDNA and uCNB analyses in this study demonstrated high sensitivity and specificity, offering promising non-invasive diagnostic options for UC. These methods also have the potential to facilitate personalized therapy, improving patient management in urothelial carcinoma.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

H. Tang, C. Jia, F. Xie, Y. Zhang, S. Jia: Financial Interests, Personal, Full or part-time Employment: Huidu. All other authors have declared no conflicts of interest.