3 | RESULTSTable 1 shows the clinic

3 | RESULTSTable 1 shows the clinical characteristics and mutational status of the cohort. Fifty-six UTUC patients (UTUC cohort), 50 patients with microscopic or macroscopic hematuria caused by other than UC (hematuria cohort), 21 patients with no evidence of disease for atleast 1 year after TURBT or RNU (UC surveillance cohort), and 26 healthy controls (HC cohort) were included in this study. Median age was 74.5 years (range: 55-92 years) in the UTUC cohort, 68 years (range: 33-89 years) in the hematuria cohort, 70 years (range: 47- 89 years) in the UC surveillance cohort, and 57 years (range: 31- 81 years) in the HC cohort. Median follow-up time was 13 months (range: 1-60 months). Of the 56 UTUC patients, 54 (96.4%) re- ceived RNU, one (1.8%) received Bacillus Calmette-Guérin therapy for carcinoma in situ of UTUC, and one (1.8%) received platinum- based chemotherapy for clinical T4 UTUC. Nineteen UTUC patients (33.9%) experienced non-invasive bladder recurrence, 12 (21.4%) progressed to metastatic disease including one patient with pT1pN1 at the time of RNU, and three (5.4%) patients died from UTUC dur- ing follow up. Hotspot mutation analysis of cfDNA in urine superna- tant extracted from all of these patients was carried out (Figure 1). The amount of cfDNA extracted from the UC surveillance cohort and HC cohort was significantly lower than that from the UTUC patients (Figure S1A). No significant difference was observed in the amount of cfDNA between high stage and low stage or highgrade and low grade (Figure S1B,C). There was no association between mutant copy number and pathological grade or stage (Figure S1D,E). Fractions of UTUC patients harboring a mutation were 22/56 (39.3%) for TERT C228T, 4/56 (7.1%) for TERT C250T, 9/56 (16.1%) for FGFR3 S249C, 5/56 (8.9%) for PIK3CA E545K, and 32/56 (57.1%) for any mutation (Table 2, Figure 2). Because the detection rate of mutant PIK3CA was very low and overlapped with othermutations, hereafter, we focus on the analysis of FGFR3 and TERT promoters (C228T and C250T). There was no association between the rate of mutation detection and smoking history, but more mutations were detected in older patients (75%, 21/28) than in younger ones (35.7%, 10/28; P = 0.031; Figure 2).