Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Ruiyun Zhang , Jingyu Zang , Haoran Tang , Feng Xie , Yue Zhang , Di Jin , Lei Qian , Tianxiang Zhang , Shidong Jia , Guanglei Zhuang , Haige Chen
Background: Bladder cancer is a common malignancy and detection of tumor recurrence is important to improve patient outcomes. Transurethral resection of bladder tumor (TURBT) is the standard treatment for early-stage bladder cancer, but the molecular detection of disease relapse remains a challenge. Reliable and non-invasive methods for monitoring the molecular changes in urine are crucial for timely intervention and disease management. Methods: In this study, 108 patients with early-stage bladder cancer who were selected for detection of disease relapse after the 1st TURBT (median timing 4.8 months after TURBT) were prospectively enrolled. The molecular recurrence in these patients was detected from the urinary tumor DNA (utDNA) using a targeted next-generation sequencing (NGS) assay (PredicineCARE). This assay identifies somatic alterations in utDNA, including single nucleotide variations (SNVs), gene fusions and copy number variations (CNVs), and based on these variations, the tumor fraction was called to identify molecular relapse in the patients. Results: 77 out of 108 (71.3%) patients were found to be tumor positive in utDNA with a tumor fraction ≥ 0.5%. The assay identified 525 SNVs and 32 CNVs in the tumor positive patients. The most frequently mutated genes in the urine samples were TP53 (38%), TERT (32%), KMT2D (28%), ARID1A (19%), FGFR3 (19%), PIK3CA (14%) and ERBB2 (12%). Conclusions: This study demonstrates the feasibility of using urine ctDNA assay to detect molecular recurrence in early-stage bladder cancer patients treated by TURBT. This information can be used to improve patient outcomes by enabling early detection of tumor recurrence and guiding treatment decisions. The findings of this study highlight the promising potential of urine-based NGS assays for cancer detection and disease surveillance.
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