Postoperative assessment using urinary tumor DNA (utDNA) to identify potential candidates for repeat transurethral resection of bladder tumor (re-TURBT) in non-muscle invasive bladder cancer (NMIBC): A retrospective analysis.

Abstract

4587 Background: The role of routine repeat transurethral resection of bladder tumor (re-TURBT) in managing non-muscle invasive bladder cancer (NMIBC) remains controversial, especially when the initial resection includes the detrusor muscle. Urinary tumor DNA (utDNA) seem really promising in urothelial carcinoma diagnosis and detection of minimal residual disease. Here, we investigated the correlation between post-initial TURBT utDNA results and the pathology of secondary resection to assess utDNA's potential for precisely identifying patients who may benefit from re-TURBT. Methods: A retrospective analysis was conducted on patients with HG Ta/T1 bladder carcinoma（BCa）who underwent re-TURBT in 2 to 6 weeks after initial TURBT at The Second Hospital of Tianjin Medical University between 2020 and 2024. All visible tumor were completely resected and detrusor muscle was collected at the initial surgery. Urine samples were collected and utDNA analysis was performed using a validated next-generation sequencing（NGS）platform a week after initial TURBT. The secondary resection includes the base of the primary tumor, resection margins, excision scar and any suspicious lesion. The results of utDNA testing were compared with the histopathology from re-TURBT. Results: 130 patients met the study inclusion criteria. Re-TURBT was successfully performed in all study participants. Urinary tumor DNA test was positive in 39 patients; of whom 35 (89.7%) showed positive repeat biopsy (HR = 7.42, 95%CI = 2.94-18.67, P < 0.001). The sensitivity, specificity, positive and negative predictive value of utDNA test for re-TURBT histopathology were 76.1%（95%CI：64-88），95.2%（95%CI：91-99），89.7%（95%CI：80-99），87.9%（95%CI：81-95），respectively. On a median（range）follow-up of 23 (3-47) months，15 cases of tumor recurrence were encountered in 14（10.7%）patients. On multivariate Cox regression analysis, the post-initial-TURBT utDNA test was significantly associated with tumor recurrence (HR = 4.48, 95%CI：2.0-9.8, P < 0.001). Conclusions: Our findings suggest that utDNA analysis after initial TURBT can effectively identify patients with residual disease who are likely to benefit from re-TURBT and that utDNA is an independent predictor of tumor recurrence. This non-invasive liquid biopsy method has the potential to identify beneficiaries of re-TURBT, and optimize the management of HG Ta/T1 bladder cancer. Further prospective studies are warranted to validate the clinical utility of utDNA in this setting.