Clinical effectiveness of a multitarget urine DNA test for urothelial carcinoma detection: a double-blinded, multicenter, prospective trial

• Published in: Molecular cancer Vol. 23; no. 1; pp. 57 - 6
• Main Authors: Wu, Junlong, Lin, Yuda, Yang, Kaiwei, Liu, Xiao, Wang, Huina, Yu, Tingting, Tao, Ran, Guo, Jing, Chen, Libin, Cheng, Huanqing, Lou, Feng, Cao, Shanbo, Yu, Wei, Hu, Hailong, Ye, Dingwei
• Format: Journal Article
• Language: English
• Published: London BioMed Central 19.03.2024; BioMed Central Ltd; BMC
• Subjects: Accuracy; Algorithms; Biomedical and Life Sciences; Biomedicine; Bladder; Cancer; Cancer biomarkers; Cancer Research; Carcinoma; Cellular biology; Clinical trials; Correspondence; Cytology; Diagnosis; DNA; drug resistance; Early detection; Fibroblast growth factor receptors; Genetic aspects; Hematuria; Latest Correspondence on Biomarkers for Cancer diagnosis; Liquid biopsy; Malignancy; Medical prognosis; Methylation; Molecular diagnosis; Mutation; Oncology; Patient compliance; Prediction models; prognosis; Sensitivity analysis; Tumors; Urinary tract; Urine; Urine tumor DNA; Urological cancer; Urothelial carcinoma; Cancer biomarkers; Liquid biopsy; Molecular diagnosis; Urothelial carcinoma; Urine tumor DNA; Early detection
• ISSN: 1476-4598; 1476-4598
• DOI: 10.1186/s12943-024-01974-4

Urine-based testing is promising for noninvasive diagnosis of urothelial carcinoma (UC) but has suboptimal sensitivity for early-stage tumors. Herein, we developed a multitarget urine tumor DNA test, UI-Seek, for UC detection and evaluated its clinical feasibility. The prediction model was developed in a retrospective cohort ( n  = 382), integrating assays for FGFR3 and TERT mutations and aberrant ONECUT2 and VIM methylation to generate a UC-score. The test performance was validated in a double-blinded, multicenter, prospective trial ( n  = 947; ChiCTR2300076543) and demonstrated a sensitivity of 91.37% and a specificity of 95.09%. The sensitivity reached 75.81% for low-grade Ta tumors and exceeded 93% in high-grade Ta and higher stages (T1 to T4). Simultaneous identification of both bladder and upper urinary tract tumors was enabled with sensitivities exceeding 90%. No significant confounding effects were observed regarding benign urological diseases or non-UC malignancies. The test showed improved sensitivities over urine cytology, the NMP22 test, and UroVysion FISH alongside comparable specificities. The single-target accuracy was greater than 98% as confirmed by Sanger sequencing. Post-surgery UC-score decreased in 97.7% of subjects. Overall, UI-Seek demonstrated robust performance and considerable potential for the early detection of UC.