Carcinoma in situ of the upper urinary tract: a scoping review mapping the evidence and research gaps

BACKGROUND: Carcinoma in situ (CIS) of the upper urinary tract (UUT) is a rare, highgrade, non-invasive urothelial neoplasm whose diagnostic and therapeutic management remains largely extrapolated from bladder CIS. No comprehensive update of the evidence has been produced since the landmark consensus review of 2017. OBJECTIVE: To systematically map the breadth, nature and gaps of the available literature on UUT-CIS, using the Population- Concept-Context (PCC) framework, focusing on diagnosis, treatment, molecular/genetic characterization and prognosis. METHODS: This scoping review followed the Arksey and O'Malley framework and was reported according to the PRISMA extension for Scoping Reviews (PRISMA-ScR). PubMed/MEDLINE, Embase, Scopus, Web of Science and the Cochrane Library were searched from January 2000 through September 2026, supplemented by guideline repositories and hand-searching of reference lists. Because scoping reviews are not eligible for PROSPERO registration, the protocol was defined a priori but not prospectively registered in a public repository; this is acknowledged as a limitation. RESULTS: Of 643 records identified, 36 sources were retained for narrative synthesis, including 28 primary or empirical studies. Computed tomography urography shows high sensitivity (92%) but poor detection of flat lesions; urinary cytology and ureteroscopic biopsy remain the diagnostic mainstays despite limited sensitivity and sampling constraints. Kidney-sparing topical therapy (bacillus Calmette-Guérin [BCG] or mitomycin reversethermal gel) achieves complete response in 59-100% of cases but with highly heterogeneous recurrence (0-70%) and progression (0-43%) rates, reflecting the absence of standardized delivery protocols. Mismatch-repair protein loss and Lynch syndrome are identified in up to 9-14% of cases, supporting universal reflex screening. Concomitant CIS is consistently reported as an independent predictor of worse recurrence-free and cancer-specific survival after radical nephroureterectomy. CONCLUSIONS: Evidence on UUT-CIS remains fragmented, predominantly retrospective and single-institutional. Five priority research gaps were identified: absence of a standardized histological/ imaging definition, lack of standardized topical-therapy protocols, scarcity of prospective long-term data, near-absence of quality-of-life/patient-reported outcomes, and underuse of molecular risk stratification. Multi-institutional prospective registries are needed to inform future evidence-based guidelines.