Postresection Urinary Tumor DNA Refines Residual Disease Assessment and Recurrence Risk Stratification in Non–Muscle-Invasive Bladder Cancer
Shiwang Huang, Zihan Xue, Ning Kang, Boyue Ma, Kaipeng Jia, Yuda Lin, Peng Li, Chong Shen, Bin Fu, Hailong Hu, Yunkai QiePurpose
Repeat transurethral resection of bladder tumor (TURBT) is recommended for selected patients with non–muscle-invasive bladder cancer (NMIBC), but clinicopathologic indications are broad and often identify no residual tumor. We tested whether postresection urinary tumor DNA (utDNA) adds value beyond guideline-derived repeat-TURBT selection and established recurrence risk models.
Materials and Methods
This guideline-anchored cohort analysis included 161 patients with NMIBC who underwent repeat TURBT. Urine was collected 2 to 6 weeks after initial TURBT and before repeat TURBT. Tissue-naïve utDNA and cytology were compared with repeat-TURBT pathology and evaluated against repeat-TURBT indication sets, European Association of Urology (EAU) risk grouping, The European Organisation for Research and Treatment of Cancer (EORTC) models, and Club Urologico Espanol de Tratamiento Oncologico (CUETO) models.
Results
Residual tumor was found in 57 patients (35.4%). Core, expanded, and carcinoma in situ-augmented core indication sets selected 73.3%, 88.2%, and 80.7% of patients. Within these indication-positive groups, utDNA-negative status identified 66.9% to 67.7% as lower-yield, although 9.1% to 10.4% still had residual tumor. Adding utDNA increased residual tumor AUCs from 0.544 to 0.891, 0.537 to 0.892, and 0.513 to 0.890 for the three indication sets, respectively. For any recurrence, c-indices increased from 0.602 to 0.774 for EAU risk grouping, 0.717 to 0.837 for EORTC models, and 0.770 to 0.824 for CUETO models after adding utDNA.
Conclusion
Postresection utDNA refined residual tumor detection beyond repeat-TURBT indication sets and improved recurrence risk stratification beyond EAU/EORTC models, with directionally consistent CUETO results. Positive utDNA after negative repeat TURBT suggested occult molecular risk and supports prospective testing of utDNA-informed resection and surveillance algorithms.