Plasma ctDNA Assay Determines Genomic Profile in Patients with Advanced UC

Circulating tumor DNA (ctDNA) analysis can serve as a noninvasive alternative to tissue biopsy for genotyping in multiple forms of cancer. A recent study has sought to determine the clinical utility of ctDNA in advanced urothelial cancer (UC) by establishing and evaluating a plasma ctDNA sequencing assay.

The study involved 82 patients diagnosed with muscle-invasive or metastatic UC, from which 158 blood samples and 73 tumors tissue samples were obtained and sequenced using the panel developed by the investigators, which included 53 UC-relevant genes as well as TERT promoter mutations.

Researchers examined the association between ctDNA fraction and response to pembrolizumab, analyzing ctDNA dynamics throughout systemic therapy.

In paired tissue and ctDNA samples, 50.2% of somatic mutations were shared by both sources, and 17.6% of mutations were only found in ctDNA. Increases in ctDNA fraction during treatment with pembrolizumab in the metastatic setting were significantly linked to poor response rates (18.7% vs 76.1%; P=0.001) and progression-free survival (median 2.8 vs 9.8 months; P<0.001).

A comparison of cancer cell fraction measured at initiation of pembrolizumab treatment and again during  continued treatment showed a strong correlation (r=0.73) in patients with increasing ctDNA fraction during treatment. Conversely, no correlation was seen in patients without a ctDNA fraction increase (r=0.09). The majority of mutations newly detected on development of pembrolizumab resistance were already present in tumor tissues at earlier stages.

This newly developed assay can assess the genomic profile of ctDNA in patients with advanced UC, and these data may support future biomarker analysis for UC.