Comparison of clinical outcomes of bladder preservation and surgery in a real-world study of patients with muscle invasive urothelial carcinoma using urine and plasma based MRD (minimal residual disease) assays.

e16580 Background: Recently, non-invasive urine/plasma-based minimal residual disease (MRD) assays have demonstrated the ability to reliably detect deep molecular alterations in bladder cancer patients. Similar to circulating tumor DNA, urinary tumor DNA (utDNA) is a noninvasive method of measuring MRD by evaluating the molecular landscape of tumor DNA shed in urine with next generation sequencing techniques. UtDNA can reflect the tumor landscape in real-time in patients with urothelial carcinoma via direct shed into the urine and can be utilized in monitoring for disease progression and also treatment response. This study investigates tissue-informed blood MRD and urine-informed urine MRD tests in the real world setting. Methods: A cohort of 40 real-world bladder and UTUC patients were included in this study. Treatment modalities such as neoadjuvant chemotherapy, trimodality therapy (TMT) for bladder preservation, and systemic chemotherapy/immunotherapy were utilized. Matching time point blood samples and urine samples were collected at variable intervals depending on the treatment regimens the patients received. Urine samples were tested using the PredicineBEACON urine MRD assay, which used the urine PredicineWES+ whole exome sequencing results from baseline urine samples for the design of a personalized MRD panel. Patients were followed up with MRD tests until otherwise censored. Results: There were a total of 94 urine and 253 plasma-based MRD tests with a success rates of over 90%, indicating the maturation of liquid biopsy lab technologies. Patients were followed for a median of 6.5 months between the first MRD assay and most recent follow up. MRD status and tumor fraction (TF) were monitored. The TF and kinetics from the urine MRD assay were in high concordance with the blood MRD assay results at matching time points. The mutation allele frequency time course changes matched with patient treatment responses and progression events in most cases. Clear increase in mutations and TF were observed in patients with progressive disease. Patients receiving definitive therapy had good disease-free survival time (longest >2 years), and there is no significant difference between bladder preservation or surgery-based intervention. Conclusions: In this study, we observed no significant difference in clinical outcomes between bladder cancer patients receiving bladder preservation or surgery-based intervention. Urine and blood-based MRD tests closely correlated with clinical outcomes. Our study emphasizes the value of serial monitoring of urine/plasma-based MRD assays in informing MRD status or treatment response for patients who undergo bladder preservation or cystectomy. The number of cases was limited in this study and further follow up will be needed to confirm the findings in this study.