Detection and surveillance of bladder cancer using urine tumor DNA

Jonathan C. Dudley, Joseph Schroers-Martin, Daniel V. Lazzareschi, William Y. Shi, Simon B. Chen, Mohammad S. Esfahani, Dharati Trivedi, Jacob J. Chabon, Aadel A. Chaudhuri, Henning Stehr, Chih Long Liu, Harumi Lim, Helio A. Costa, Barzin Y. Nabet, Joseph C. Liao, Ash A. Alizadeh, Ash A. Alizadeh

Research output: Contribution to journalArticlepeer-review

136 Scopus citations


Current regimens for the detection and surveillance of bladder cancer 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 bladder cancer who had urine collected either prior to treatment or during surveillance. Using this targeted sequencing approach, we detected a median of 6 mutations per patient with bladder cancer and observed surprisingly frequent mutations of the PLEKHS1 promoter (46%), suggesting these mutations represent a useful biomarker for detection of bladder cancer. We detected utDNA pretreatment in 93% of cases using a tumor mutation-informed approach and in 84% when blinded to tumor mutation status, with 96% to 100% specifi city. 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 ≤ 0.006), detecting 100% of bladder cancer 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 bladder cancer.

Original languageEnglish
Pages (from-to)500-509
Number of pages10
JournalCancer discovery
Issue number4
StatePublished - Apr 2019


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