Next-generation sequencing (NGS) of cell-free circulating tumor DNA and tumor tissue in patients with advanced urothelial cancer: a pilot assessment of concordance

Abstract

Background: Advances in cancer genome sequencing have led to the development of various next generation sequencing (NGS) platforms. There is paucity of data regarding concordance of different NGS tests performed in the same patient.Methods: Here, we report a pilot analysis of 22 patients with metastatic urinary tract cancer and available NGS data from paired tumor tissue [FoundationOne (F1)] and cell-free circulating tumor DNA (ctDNA) [Guardant360 (G360)].Results: The median time between the diagnosis of stage IV disease and the first genomic test was 23.5 days (0-767), after a median number of 0 (0-3) prior systemic lines of treatment for advanced disease. Most frequent genomic alterations (GA) were found in the genes TP53 (50.0%), TERT promoter (36.3%); ARID1 (29.5%); FGFR2/3 (20.5%), PIK3CA (20.5%) and ERBB2 (18.2%). While we identified GA in both tests, the overall concordance between the two platforms was only 16.4% (0-50%), and 17.1% (0-50%) for those patients (n = 6) with both tests conducted around the same time (median difference= 36 days). On the contrary, in the subgroup of patients (n = 5) with repeated NGS in ctDNA after a median of 1 systemic therapy between the two tests, average concordance was 55.5% (12.1-100.0%). Tumor tissue mutational burden was significantly associated with number of GA in G360 report (p<0.001), number of known GA (p = 0.009) and number of variants of unknown significance (VUS) in F1 report (p<0.001), and with total number of GA (non-VUS and VUS) in F1 report (p<0.001).Conclusions: This study suggests a significant discordance between clinically available NGS panels in advanced urothelial cancer, even when collected around the same time. There is a need for better understanding of these two possibly complementary NGS platforms for better integration into clinical practice.

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