Urothelial Cancer

In this carefully selected elderly MIBC patient, neoadjuvant enfortumab vedotin combined with toripalimab was well tolerated and associated with marked tumor regression and a favorable pathological response on post-treatment TURBT. Bladder preservation was attempted, illustrating the feasibility of this regimen and generating a hypothesis for future investigation.

FGFR3 mutation was not detected in any of the cases. Urothelial carcinomas occurring in children and young adults exhibit a distinct molecular profile compared with those in older patients, characterized by a higher frequency of HRAS mutations and a significantly lower prevalence of TERT promoter and FGFR3 alterations.

MYC OE defines a lethal subtype with aggressive behaviors and therapeutic resistance in UC patients. Our findings highlight the need for tailored therapeutic strategies for this refractory subtype of UC.

These findings indicated that SOX2 expression represents an independent and robust prognostic biomarker in UTUC, identifying a biologically distinct high-risk subgroup with unfavorable clinical outcomes. The preserved expression of PD-L1 and ADC targets in this subgroup may suggest potential responsiveness to immune checkpoint inhibitors and ADC-based therapies, supporting the consideration of intensified perioperative or systemic treatment strategies in SOX2-positive patients.

RNA-based, DNA methylation-based, protein-based, and ctDNA-based assays showed promise for UTUC diagnosis and risk stratification. However, the current evidence is limited, with few validated studies. Large prospective cohorts and biomarker-driven interventional trials are needed before clinical integration.

Ancillary modalities, including immunohistochemistry (e.g., CK20, p53, CD44) and emerging molecular tests, are appraised for their utility and constraints. Finally, the review highlights emerging computational tools-particularly artificial intelligence-based analysis of histopathology slides, which shows considerable promise in enhancing diagnostic accuracy-and concludes with evidence-based recommendations aimed to optimize the management of flat urothelial lesions.

P1, N=158, Recruiting, Avacta Life Sciences Ltd | Trial primary completion date: Mar 2026 --> Jun 2026

P1, N=154, Terminated, M.D. Anderson Cancer Center | Trial completion date: Oct 2026 --> May 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Oct 2026 --> May 2026; < 75 % participation

P=N/A, N=200, Recruiting, Peking University First Hospital | Not yet recruiting --> Recruiting

P2, N=50, Not yet recruiting, RenJi Hospital

P1/2, N=144, Not yet recruiting, G.O.I.R.C. Gruppo Oncologico Italiano Di Ricerca Clinica

In conclusion, tumor HER2 expression may identify a subgroup of patients with advanced UC at increased risk of recurrence and cancer-specific mortality, supporting its potential role as a prognostic biomarker. However, standardized assessment and prospective studies are warranted to define its utility for risk stratification and therapeutic targeting.