Abstract 753P
Background
Current methods for the detection and surveillance of bladder cancer (BCa) are often invasive and/or possess suboptimal sensitivity and specificity. Novel sensitive methods for detection of early stage, minimal, residual or recurrent tumors may achieve a great improvement on treatment and outcome for patients with BCa.
Methods
We developed a novel method for the detection of urine tumor DNA Methylation at multiple genomic regions by Mass Array, termed utMeMA. We identified the BCa-specific methylation markers by combined analyses of Sun Yat-sen Memorial Hospital (SYSMH), TCGA and GEO cohorts. The BCa diagnostic model was built in a retrospective cohort (n=313) and validated in a multicenter, prospective cohort (n=175). The performance of this diagnostic assay was analyzed and compared with urine cytology and FISH.
Results
We first discovered 26 significant methylation markers of BCa in combined analyses. We build and validate a two-marker-based diagnostic model that discriminated patients with BCa with high accuracy (86.7%), sensitivity (90.0%) and specificity (83.1%). Furthermore, utMeMA based assay achieved a great improvement in sensitivity over urine cytology and FISH, especially in the detection of early stage (Ta and low grade tumor, 64.5% vs. 11.8%, 15.8%), minimal (81.0% vs. 14.8%, 37.9%), residual (93.3% vs. 27.3%, 64.3%) and recurrent (89.5% vs. 31.4%, 52.8%) tumors. The urine diagnostic score (UD-score) from this assay was better associated with tumor malignancy and burden.
Conclusions
Urine tumor DNA methylation assessment for early diagnosis, minimal, residual tumor detection and surveillance in bladder cancer is a rapid, high-throughput, non-invasive and promising approach, which may reduce the burden of cystoscopy and blind second surgery.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Sun Yat-sen Memorial Hospital, Sun Yat-sen University.
Funding
AnchorDx Medical Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.