Table 1.
Key urine-based liquid biopsy studies for diagnosis and preoperative triage.
| Study | Biomarker/assay | Setting | Key finding | Potential relevance to KSS | Main limitation |
|---|---|---|---|---|---|
| Freund et al., 2018 (51) | UroVysion FISH | Selective upper-tract urine; surveillance/triage | Sensitivity 90%, specificity 80% in a feasibility setting. | Could reduce unnecessary follow-up URS after KSS. | Very small cohort. |
| Hayashi et al., 2019 (60) | TERT/FGFR3 urinary cfDNA | Preoperative diagnosis and stage enrichment | FGFR3 signal associated with ≤pT1 disease; combined assay improved diagnostic performance. | Suggests biologically informative urine profiling beyond cytology. | Panel limited; exploratory stage signal. |
| Xu et al., 2021 (61) | 17-gene mutation panel + ONECUT2 methylation | Preoperative detection | High diagnostic accuracy in suspected UTUC. | May improve triage before invasive work-up. | Internal validation only. |
| Territo et al., 2022 (55) | Urine methylation panel | Prospective diagnostic setting | Outperformed cytology, especially for high-grade disease. | Useful adjunct when false-negative cytology is a concern. | Single-centre. |
| Ouyang et al., 2022 (62) | Point mutation + methylation model | Hematuria/diagnostic triage | Promising discrimination in multicentre framework. | Supports integrated molecular triage before URS. | Diagnosis-focused, not outcome-guiding. |
| Ghoreifi et al., 2023 (49) | DNA methylation marker test | Prospective cohort | High sensitivity and specificity for UTUC detection. | Clinically relevant adjunct to preoperative triage. | Direct KSS outcome data unavailable. |
| Palermo et al., 2024 (57) | Bladder EpiCheck | Selective upper-tract urine | Particularly strong signal for high-grade disease. | May enrich for lesions less suitable for conservative management. | Limited outcome linkage. |
| Wei et al., 2024 (58) | Urine liquid biopsy, self-matched design | Preoperative detection | Markedly higher sensitivity than cytology. | Reduces false reassurance before KSS decisions. | Small cohort. |
| Zhang et al., 2024 (22) | 8-gene RNA panel | Prospective multicentre validation | Robust noninvasive discrimination before treatment. | One of the strongest current pre-URS triage data sets. | Still not a standalone KSS selector. |
| Yang et al., 2026 (50) | UroCAD copy-number assay | Prospective multicentre study | High diagnostic performance; CNV burden may correlate with aggressiveness. | Potentially valuable for risk enrichment beyond simple detection. | Needs broader external and decisional validation. |
| Fujita et al., 2026 (63) | Oncuria-Detect multiplex immunoassay | Noninvasive detection | High sensitivity/NPV profile. | Likely more useful for suspicion triage than definitive selection. | Specificity more modest than sensitivity. |
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.