DNA methylation analysis in urinary samples is associated with recurrence and grade progression in selected patients with pT1 low-grade urothelial bladder carcinoma

Low-grade urothelial carcinoma (LGUC) has a lower risk of recurrence and grade progression than high-grade urothelial carcinoma (HGUC), although a subset of patients may develop recurrent disease and/or grade progression. The Bladder EpiCheck test (Nucleix Ltd) analyzes 15 DNA methylation biomarkers and provides a score, termed EpiScore. In this retrospective study, urine cytology and urinary methylation analysis were performed in 78 patients who subsequently received a histological diagnosis of LGUC. Patients were followed after treatment with cystoscopy and voided urine cytology every 6 months for 1 to 2 years. During follow-up, 31 of 78 patients (40%) developed recurrent disease, including 7 cases with progression to HGUC. No recurrence was observed in 47 of 78 patients (60%). At first diagnosis, an EpiScore ≥ 60 was associated with recurrent neoplasia (p < 0.0001). Progression to HGUC was observed only among patients with an EpiScore ≥ 60, although this finding should be interpreted cautiously because of the limited number of progression events and the absence of events in the EpiScore < 60 group. In conclusion, urinary methylation analysis may identify a subgroup of patients with LGUC associated with recurrence and grade progression to HGUC. These findings are exploratory and require prospective validation in larger and more heterogeneous cohorts.