2397P - A real-world study of longitudinal urinary ctDNA monitoring of minimal residual disease (MRD) in patients with muscle invasive urothelial carcinoma followed in parallel with plasma based ctDNA

Background

Recently, non-invasive urine-based MRD assays have demonstrated the ability to detect deep molecular alterations in bladder cancer patients, which may greatly improve disease monitoring and treatment stratification. In this study, we carried out both tissue-informed blood and urine-informed urine based MRD tests for a cohort of 30 real-world high risk bladder and UTUC patients and studied their concordance to clinical responses.

Methods

30 real-world bladder and UTUC patients of various subtypes were included in this study. Standard treatment modalities such as neoadjuvant chemotherapy, trimodality therapy (TMT) for bladder preservation, and systemic chemotherapy/immunotherapy were utilized. All patients with sufficient tissue had a Signatera™ blood-based MRD assay, for which FFPE tumor tissues were also tested to establish a baseline. Blood and urine samples were collected at variable intervals depending on the treatment regimens the patients received. The urine samples were tested using the PredicineBEACON™ urine MRD assay, which used the urine PredicineWES+™ whole exome sequencing results of the baseline urine sample for the design of personalize MRD panel tracking up to 50 mutations in addition to a fixed panel of 500 actionable mutations.

Results

The urine based MRD test had over a 90% testing success rate in detection of molecular alterations specific to urinary tract tumors. The tumor fraction (TF) estimate and kinetics from the urine MRD assay were in high concordance with the blood MRD assay results along with treatment responses and progression events in most cases. In several patients, the urine-based MRD assay detected mutations that were not detected in baseline tissue or blood based testing.

Conclusions

Urine-based MRD assays had highly concordance with blood based MRD. Besides its convenience in sample collection, urine-based genomic profiling also has the potential to capture more heterogeneity of urinary tract malignancies as compared to tissue or blood based testing alone. Urine ctDNA monitoring is a useful complementary test to support standard tissue and plasma based assays in high risk bladder and UTUC patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Rush University Medical Center.

Funding

Has not received any funding.

Disclosure

A. Tan: Financial Interests, Personal, Advisory Board: Exelixis, Natera; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Merck, EMD Serono, Myovant, Gilead, Regeneron; Financial Interests, Personal, Stocks/Shares: Natera.