Revolutionizing bladder cancer follow-up: Personalized urinary ctDNA analysis for detecting minimal residual disease.

Abstract

4584 Background: As one of the most common malignant neoplasms of the urinary tract, bladder cancer (BC) has received widespread attention with respect to high incidence and tend to recur and progress. Circulating tumor DNA (ctDNA) serves as a valuable tool for detecting and monitoring minimal residual disease (MRD). Here, we conducted a prospective study to assess the potential of urinary ctDNA (utDNA) as a biomarker for measuring MRD in patients for non-muscle-invasive bladder cancer (NMIBC). The objective of this study was to evaluate the utility of longitudinal utDNA in informing adjuvant therapy decisions, enhancing clinical monitoring strategies, and ultimately improving BC prognosis. Methods: A total of 67 patients diagnosed with stage I-IV BC were recruited for the study from 2022.11 to 2024.12. For each patient, a customized panel was developed and synthesized, encompassing up to 45 baseline mutations, including SNVs and Indels. In addition to the patient-specific panel, a standardized core panel targeting hotspot regions was incorporated. Whole exome sequencing (WES) was conducted on cancer tissue samples and blood leukocytes in order to reduce the risk of false-positive findings and to exclude potential germline mutations, respectively. Results: The study cohort consisted of 59 patients diagnosed with BC, 7 patients with renal pelvis cancer, and 1 patient with ureteral cancer. 59 individuals, accounting for 88% of the sample, had a median age of 65 years. UtDNA was identified in 64 out of 67 preoperative patients, resulting in a detection rate of 95.5%. Furthermore, the correlation between urine samples and tissue samples was confirmed by Pearson's correlation analysis, yielding a correlation coefficient of (r = 0.31). 10 patients (14.9%) experienced a recurrence following TURBT. Residual tumors were detected in 7 of the recurrent patients who tested positive for urinary utDNA, accounting for 70% of the cases (7/10). Notably, the presence of positive utDNA in urine samples was observed 3 to 8 months prior to any indications on imaging studies. Monitoring of MRD demonstrated a consistent reduction in utDNA concentrations following surgery. Among patients with complete remission (CR), 9 individuals who initially tested positive for MRD post-surgery subsequently tested negative. Conclusions: The findings revealed a high level of concordance between the mutations identified in the tumor and those detected in the utDNA. Patients with positive utDNA exhibited a greater risk of cancer recurrence compared to those who tested negative for utDNA. Urine-personalized MRD detection strategies are anticipated to enhance the efficacy of adjuvant therapy and improve prognostic assessments in patients with BC. None. Clinical trial information: ChiCTR2400079704 .