Potential of Urinary Mutation and Methylation Biomarkers in Selecting Candidates for Repeat Transurethral Resection of Bladder Tumor in Non-muscle-invasive Bladder Cancer: A Prospective Multicenter Study

Xiao Yang; Lingkai Cai; Yaqun Xin; Xinfeng Chen; Bing Zheng; Jie Han; Lin Yuan; Xuejian Yang; Pengchao Li; Juntao Zhuang; Peikun Liu; Ruixi Yu; Rongjie Bai; Yiyang Liu; Tonghui Ma; Qiang Cao; Qiang Lu

doi:10.1016/j.euros.2025.05.011

Potential of Urinary Mutation and Methylation Biomarkers in Selecting Candidates for Repeat Transurethral Resection of Bladder Tumor in Non-muscle-invasive Bladder Cancer: A Prospective Multicenter Study

Eur Urol Open Sci. 2025 Jun 10:77:49-57. doi: 10.1016/j.euros.2025.05.011. eCollection 2025 Jul.

Authors

Xiao Yang¹, Lingkai Cai^{1

2}, Yaqun Xin³, Xinfeng Chen⁴, Bing Zheng⁴, Jie Han⁵, Lin Yuan⁵, Xuejian Yang⁶, Pengchao Li^{1

6}, Juntao Zhuang¹, Peikun Liu¹, Ruixi Yu¹, Rongjie Bai¹, Yiyang Liu¹, Tonghui Ma⁷, Qiang Cao¹, Qiang Lu¹

Affiliations

¹ Department of Urology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
² Department of Urology, Wuxi Medical Center of Nanjing Medical University, Wuxi, China.
³ Hangzhou Jichenjunchuang Medical Laboratory, Hangzhou, China.
⁴ Department of Urology, Nantong First People's Hospital, Nantong, China.
⁵ Department of Urology, Jiangsu Province Hospital of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
⁶ Department of Urology, Suqian First Hospital, Suqian, China.
⁷ Genecn-Biotech, Hangzhou, China.

Abstract

Background and objective: The necessity of repeat transurethral resection of bladder tumor (re-TURBT) in patients with non-muscle-invasive bladder cancer (NMIBC) remains a matter of debate. The role of liquid biopsy in predicting residual tumor status and selecting patients who can be spared re-TURBT is still undefined. The aim of our study was to assess the efficacy of the urinary OncoUrine assay for mutation and methylation markers in determining the necessity for re-TURBT in NMIBC.

Methods: We prospectively recruited patients with NMIBC who were candidates for re-TURBT. Urine samples for OncoUrine testing and exfoliated cytology analysis were collected after initial TURBT, followed by re-TURBT.

Key findings and limitations: Among 151 patients with NMIBC, 48 (32%) had residual tumor at re-TURBT, and 87 (58%) had detrusor muscle (DM) in their initial TURBT specimen. The OncoUrine test showed sensitivity of 77%, specificity of 78%, positive predictive value of 62%, and negative predictive value (NPV) of 88% for residual tumor, while exfoliated cytology showed corresponding values of 20%, 96%, 69%, and 72%. Stratified analyses revealed higher OncoUrine accuracy in predicting disease-free status in intermediate-risk NMIBC (NPV 98%) and in high-risk NMIBC cases with DM in the initial TURBT specimen (NPV 92%). At 18-mo follow-up for 131 patients, 20 had experienced tumor recurrence, for which OncoUrine positivity was the only independent factor predictive for the risk of recurrence (hazard ratio 3.67, 95% confidence interval 1.49-9.00; p = 0.005).

Conclusions and clinical implications: The OncoUrine test may identify patients who can avoid unnecessary re-TURBT, especially for intermediate-risk NMIBC cases and high-risk NMIBC cases with DM in the initial TURBT specimen. Conversely, patients with a positive OncoUrine result are at higher risk of recurrence and should undergo re-TURBT.

Patient summary: OncoUrine is a urine test that can help in identifying patients with non-muscle-invasive bladder cancer who may be able to avoid unnecessary repeat resection of the bladder.

Keywords: Methylation; Mutation; Non–muscle-invasive bladder cancer; Recurrence; Repeat transurethral resection of bladder tumor; Residual tumor; Urine liquid biopsy.