Work

Trophoblastic-Differentiated Urothelial Carcinoma: Real-World Sequencing and Clinical Implications

Year: 2026

Type: article

Abstract: Introduction Urothelial carcinoma with trophoblastic differentiation (TUC) is a rare, aggressive variant reported in the upper and lower urinary tract, but its genomic landscape remains poorly defined. We aimed to define the genomic features of this uncommon histologic variant by evaluating results from clinical next-generation sequencing. Methods We retrospectively identified patients with pathologically confirmed TUC at our institution from 2020–2025. Patients were included if they underwent standard-of-care comprehensive genomic profiling (Signatera). Clinicopathologic data and tumor mutational burden (TMB) were abstracted from reports. Follow-up, overall survival, and recurrence-free survival were assessed. Results Eighteen patients had confirmed TUC (median age 75); 88.9% were male and 83.3% White. Disease was advanced at surgery (pT2–pT4, 66.7%) and 50% were node-positive. Median follow-up was 12.85 months with 27.8% deaths; OS was 88.5% at 6 months and 62.6% at 12/18 months overall. Genomics (n=5) showed MSI-stable, low–intermediate TMB (median 2 mut/Mb) and a largely luminal–papillary, FGFR3-driven profile. Conclusion TUC shows low-to-intermediate TMB and recurrent alterations in TERT and multiple canonical urothelial carcinoma genes, with occasional atypical co-mutations. Larger genomic studies are needed to clarify biology and guide targeted therapy development.

Source: Clinical Genitourinary Cancer

DOI: 10.1016/j.clgc.2026.102592