Detection and surveillance of bladder cancer using urine tumor DNA. Cancer discovery Dudley, J. C., Schroers-Martin, J. n., Lazzareschi, D. V., Shi, W. Y., Chen, S. B., Esfahani, M. S., Trivedi, D. n., Chabon, J. J., Chaudhuri, A. A., Stehr, H. n., Liu, C. L., Lim, H. n., Costa, H. A., Nabet, B. Y., Sin, M. L., Liao, J. C., Alizadeh, A. A., Diehn, M. n. 2018


Current regimens for the detection and surveillance of bladder cancer (BLCA) are invasive and have suboptimal sensitivity. Here, we present a novel high-throughput sequencing (HTS) method for detection of urine tumor DNA (utDNA) called utDNA CAPP-Seq (uCAPP-Seq) and apply it to 67 healthy adults and 118 patients with early-stage BLCA who either had urine collected prior to treatment or during surveillance. Using this targeted sequencing approach, we detected a median of 6 mutations per BLCA patient and observed surprisingly frequent mutations of the PLEKHS1 promoter (46%), suggesting these mutations represent a useful biomarker for detection of BLCA. We detected utDNA pre-treatment in 93% of cases using a tumor mutation-informed approach and in 84% when blinded to tumor mutation status, with 96-100% specificity. In the surveillance setting, we detected utDNA in 91% of patients who ultimately recurred, with utDNA detection preceding clinical progression in 92% of cases. uCAPP-Seq outperformed a commonly used ancillary test (UroVysion, p=0.02) and cytology and cystoscopy combined (p is less than or equal to 0.006), detecting 100% of BLCA cases detected by cytology and 82% that cytology missed. Our results indicate that uCAPP-Seq is a promising approach for early detection and surveillance of BLCA.

View details for PubMedID 30578357