Urine DNA for monitoring chemoradiotherapy response in muscle-invasive bladder cancer: a pilot study | Gordon NS, et al | BJU international | Jan. 2022

Overview:

Accumulating evidence implies the utility of DNA-based urine biomarkers for initial detection of bladder cancer (BC) and surveillance of non-muscle-invasive BC. We have previously described gene panels with utility for these indications, identifying UBC-associated mutations in 96% of all BCs, such that the associated urine test is not reliant on the initial identification of mutations in primary tumour tissue. By contrast, the utility of urine as a liquid biopsy for the surveillance of patients with muscle-invasive BC (MIBC) treated by bladder preservation (radiotherapy  chemotherapy) remains understudied; one previous publication describes microsatellite analysis of urinary DNA to detect bladder recurrences in five out of six radiotherapy patients.

We undertook a pilot study to evaluate whether measuring common BC-associated mutations in urinary DNA can contribute to the monitoring of treatment responses in patients with organ-confined MIBC treated with curative intent.

In summary, two out of the four patients who relapsed (three local, one distant, 3–9 months after completing treatment) had undetectable urinary VAFs on treatment completion. This finding is particularly surprising for the two out of three bladder recurrences with undetectable urinary VAFs on treatment completion given that, in other cancer settings, the ‘clearance of mutations’ in liquid biopsy samples is associated with significantly improved outcomes.

Methodologically, both targeted capture-based and PCR-based library preparation and next-generation sequencing can be used to identify common BC-associated mutations in urinary cpDNA.

Urine DNA for monitoring chemoradiotherapy response in muscle-invasive bladder cancer: a pilot study