2402P - Urine-based comprehensive genomic profiling reveals mutational landscape in real-world patients with bladder cancer

Background

Bladder cancer is the most prevalent form of urothelial carcinoma. There is an urgent need for timely and accurate identification of molecular alterations to guide tailored therapeutic treatment. Urinary tumor DNA (utDNA) analysis not only holds promise as a valuable tool in bladder cancer diagnosis and monitoring, but also has the potential to identify actionable mutations that can be targeted with personalized therapies.

Methods

This prospective study enrolled 154 patients with bladder cancer in real-world settings, comprising 65 patients with non-muscle invasive bladder cancer (NMIBC) and 89 patients with muscle invasive bladder cancer (MIBC). The cohort included treatment-naive patients as well as those who had received treatment and were at risk of recurrence. Urine samples were collected from each patient. PredicineCARE, a NGS liquid biopsy assay, was applied to detect somatic alterations in urinary tumor DNA (utDNA).

Results

The study detected a total of 368 somatic mutations and 14 copy number variants in 65 NMIBC patients, and 485 somatic mutations and 43 copy number variants in 89 MIBC patients. Among NMIBC patients, the most frequently mutated genes were TP53 (38%), TERT (37%), ARID1A (22%), and BRCA2 (20%). Among MIBC patients, the most frequently mutated genes were TP53 (57%), TERT (39%), ERBB2 (24%), ARID1A (20%), and PIK3CA (20%). The prevalence of FGFR2/3 variations was 15% in NMIBC and 13% in MIBC among all patients, while 38.5% of NMIBC patients and 26.3% of MIBC patients who were confirmed to be treatment-naïve harbored FGFR2/3 variations. The prevalence of ERBB2 and TP53 mutations was significantly higher in MIBC than in NMIBC (ERBB2: 21/89 vs. 4/65, p<0.01; TP53: 51/89 vs. 25/65, p<0.05). Conversely, the prevalence of RARA was significantly higher in NMIBC than in MIBC (5/65 vs. 0/89, p<0.05).

Conclusions

The present study unveils a comprehensive mutational landscape of non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) utilizing urine samples from real-world patients. These results demonstrate the promising potential of urine-based next-generation sequencing (NGS) assays to identify tumor-derived variants for clinical diagnosis and targeted treatment.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.