Cystoscopy remains the gold standard for initial diagnostic assessment and follow-up in bladder cancer (BC) patients. Novel diagnostic tools and biomarkers are needed to minimize reliance on cystoscopies whenever possible. Bladder EpiCheck® (BE) represents one such approach with encouraging results. However, its diagnostic performance at primary BC diagnosis and its effectiveness across distinct non-muscle-invasive BC (NMIBC) risk groups during follow-up have not yet been described.
Prospective case-control study between July 2018 and December 2024 including two cohorts: cohort 1 comprised individuals during primary diagnosis of BC (n = 254); cohort 2 included BC patients in follow-up for disease recurrence (n = 138). Overall, 415 voided urine samples were collected (n = 254 for cohort 1; n = 161 for cohort 2) and analyzed using BE test (Nucleix Ltd). Urine cytology was conducted whenever sufficient residual urine was available. Diagnostic performance of both techniques in detecting BC was compared.
Overall, BE sensitivity (SN) for detecting primary BC and recurrent NMIBC was 73% and 55%, respectively. When limited to high-grade (HG) tumours, BE SN increased to 92% and 87%, respectively. BE showed comparable specificity (SP) to cytology in primary (99% vs. 100%) and in recurrent tumours (91% vs. 100%). Diagnostic performance of BE was significantly better than that of cytology in primary (p = 0.013) and recurrent patients (p = 0.023). BE and cytology SN increased progressively across higher NMIBC risk groups. However, BE SN ranged from 47% in low-risk to 93% in very-high risk NMIBC patients while cytology SN ranged from 0% to 79%. Strikingly, EpiScore values were higher in those BC patients in follow-up who progressed into a muscle-invasive disease (p < 0.001), and patients with an EpiScore ≥ 90 were more likely to present high/very-high risk NMIBC or MIBC (OR = 1.93; 95% CI: 1.01-3.67; p = 0.046), ≥T1 stage (OR = 2.00; 95% CI: 1.09-3.71; p = 0.026) and HG tumours (OR = 2.59; 95% CI: 1.27-5.29; p = 0.008).
During initial diagnosis of BC, BE showed higher SN with similar SP compared with urine cytology. Diagnostic performance of BE increased gradually across EAU prognostic NMIBC factor risk classification, outperforming cytology in all risk groups. Moreover, EpiScore values are able to identify high risk BC patients, ≥T1 tumours and HG tumours.
Journal of translational medicine. 2026 May 18 [Epub ahead of print]
Marcel Figueras, Mercedes Ingelmo-Torres, Fiorella L Roldan, Emma Gomà, Pilar Galve, Clàudia Mercader, Lluís Peri, Agustin Franco, Ignacio Asiain, Antonio Alcaraz, Lourdes Mengual
Department and Laboratory of Urology, Hospital Clínic Barcelona, Barcelona, Spain., Department and Laboratory of Urology, Hospital Clínic Barcelona, Barcelona, Spain. .