Table 4.

Key plasma and urinary tumor DNA studies in perioperative UTUC management.

Study	Analyte/timing	Clinical question	Key finding	KSS/perioperative implication
Hayashi et al., 2019 (60)	Urinary cfDNA (TERT/FGFR3), preoperative	Can urinary tumor DNA enrich for lower-stage disease?	FGFR3 mutation detected only in ≤pT1 tumours; cytology combination improved performance.	Supports biologic staging at the front end of a KSS pathway.
Nakano et al., 2022 (23)	Plasma ctDNA, perioperative	Can ctDNA identify poor-prognosis localized UTUC?	Preoperative ctDNA fraction >2% and postoperative ctDNA positivity were associated with poorer outcomes.	Highlights biological risk not fully captured by conventional work-up.
Huelster et al., 2024 (24)	Plasma ctDNA + copy-number burden, preoperative	Can ctDNA predict muscle-invasive/non–organ-confined disease?	ctDNA and CN burden predicted MI/NOC disease before surgery.	Most direct evidence that plasma ctDNA may challenge conservative-treatment reassurance.
Tamura et al., 2024 (25)	Tumor-informed plasma/urinary ctDNA, postoperative	Can longitudinal ctDNA detect recurrence early?	Serial individualized monitoring detected postoperative recurrence dynamics.	Supports molecularly informed surveillance after KSS or RNU.
Powles et al., 2021/2024 (26, 66)	Postoperative ctDNA in urothelial carcinoma	Does ctDNA identify residual-risk states relevant to adjuvant treatment?	ctDNA positivity marked poorer prognosis and informed benefit signal in adjuvant setting.	Translational support for MRD-oriented escalation in UTUC.

KSS, kidney-sparing surgery; RNU, radical nephroureterectomy; URS, ureteroscopy; CTU, computed tomography urography; ctDNA, circulating tumor DNA; cfDNA, cell-free DNA; MRD, molecular residual disease; NOC, non–organ-confined; CNV, copy-number variation.