Upper tract urothelial carcinoma (UTUC) presents a clinically important gap in urologic oncology: treatment intensity is determined before surgery, yet conventional preoperative risk stratification remains imperfect. Kidney-sparing surgery (KSS) is established for selected low-risk disease and is increasingly considered when renal preservation is clinically important, but safe selection depends on distinguishing technically manageable tumors from biologically unsuitable disease. Computed tomography urography (CTU), cytology, ureteroscopy, and ureteroscopic biopsy remain indispensable, although they describe anatomy and morphology more reliably than tumor biology. Urine-based liquid biopsy platforms, including DNA methylation, mutational, multiplex RNA, copy-number, and protein assays, appear most mature for noninvasive detection and preoperative triage. Plasma circulating tumor DNA (ctDNA), in contrast, appears more closely linked to biological upstaging, occult muscle-invasive or non-organ-confined disease, perioperative risk refinement, and molecular residual disease surveillance. This review follows the KSS decision chain from patient selection to postoperative monitoring. We emphasize that current evidence supports liquid biopsy as an adjunctive, decision-enhancing layer rather than a replacement for imaging, ureteroscopy, pathology, or multidisciplinary judgment. Future studies should move beyond isolated sensitivity and specificity estimates and test whether biomarker-informed pathways improve treatment allocation, renal preservation, surveillance burden, and oncologic outcomes.
Frontiers in oncology. 2026 Jun 02*** epublish ***
Difei Yu, Jiarun Tang, Yu Zhang, Ke Hu, Jing Qing, Jiamo Zhang
Department of Urology, The Affiliated Yongchuan Hospital of Chongqing Medical University, Chongqing, Yongchuan, China.