Besides TERT promoter mutation, we

Besides TERT promoter mutation, we selected FGFR3 muta-tion as an additional biomarker candidate. Sfakianos et al reported that 30.4% of tissue from UTUC harbors a FGFR3 S249C hotspot mutation, and most of the FGFR3 mutations were detected in non- muscle-invasive UTUC.15 Consistent with a previous report, in the present study, all FGFR3 S249C mutations were detected at the early stage (at most pT1) of UTUC. It is difficult to accurately diagnose the pathological stage with CT or magnetic resonance imaging, es- pecially in ureteral tumors, because the muscle layer of the ureter is very thin. Guidelines of the European Association of Urology rec- ommend carrying out ureteroscopy for pathological staging6 and to offer ureteroscopic nephron-sparing surgery for patients with low-risk UTUC. In this study, the sensitivity and PPV for detecting≤T1 tumor by FGFR3 S249C were 32.1% and 100.0%, respectively. Although the sensitivity is relatively low, a positive result of an FGFR3 mutation in urinary cfDNA could help to predict a low-stage tumor as a liquid biopsy not requiring tissue examination. This assay for FGFR3 mutation may have the potential to become an alternative for ureteroscopy and a reliable factor for deciding whether to carry out ureteroscopic nephron-sparing surgery.This study has several limitations because of its small population size and short follow-up period. The median age of the hematuria co- hort is significantly younger than that of the UTUC cohort.