207P - Concordance of genomic alterations by next-generation sequencing in tumour tissue versus circulating tumour DNA in urothelial carcinoma

Background

Genomic alterations guided treatment are increasingly common in urothelial carcinoma (UC), but patients for whom tumor tissue is not available are not benefited from that. Molecular testing of circulating tumor DNA (ctDNA) in plasma enables the detection of mutations for patients with unavailable tumor specimens. In this study, the aim of this study was to assess whether the genomic alterations of UC detected via ctDNA is similar to tumor tissue DNA.

Methods

Patients diagnosed with UC were enrolled in the study. 49 serial plasma and matched tissue from participants were deeply sequenced via next-generation sequencing (NGS) techniques with Acornmed panel (2.0 Mbp) containing 808 cancer-related genes.

Results

A total of 49 patients were enrolled. Overall, 93.9% (46/49) patients had genomic alterations in both ctDNA and tissue DNA. For 91.3% (42/46) patients, at least one concordant mutation was detected in both ctDNA and tissue DNA. Combined ctDNA and tissue analysis identified clinical actionability, 61.2% of UC patients harbored at least one actionable alteration according to the OncoKB database via ctDNA, whereas tissue DNA was 83.7%. The concordance for the detection of clinical actionability in ctDNA and tissue DNA was 73.2%. The most common genes altered in ctDNA were TP53 (39%) and KMT5A (33%), whereas tissue DNA were TP53 (54%) and KMT2D (46%). The concordance rate between ctDNA and tissue DNA alterations was 72.2% for TP53, 66.7% for KMT5A, and 60.9 % for KMT2D, respectively. There was no statistically significant difference for gene between ctDNA and tissue DNA.

Conclusions

NGS for ctDNA and tissue revealed genomic alterations in most patients. The genomic results of ctDNA and tissue overlapped, suggesting that among patients with UC for whom no tumor tissue was available, cfDNA was able to identify a similar profile of genomic alterations compared with tumor tissue.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

W. Wang, H.H. Liu, T. Zhou, H. Wang, F. Lou, S. Cao: Full/Part-time employment: Beijing Acornmed Biotechnology Co., Ltd.