Detection of Cancer Mutations by Urine Liquid Biopsy as a Potential Tool in the Clinical Management of Bladder Cancer Patients

SIMPLE SUMMARY: The management of bladder cancer faces multiple challenges concerning the diagnostic and follow-up approaches. The standard diagnostic examination comprises invasive cystoscopy. Urine cytology and recently proposed urine-based biomarkers have been unable to replace cystoscopy, thus prompting calls for improvements. Here, we explore urine liquid biopsy to detect cancer mutations and subsequently evaluate the utility of urine as a suitable specimen for diagnosing bladder cancer. Our results show that the analysis of pre- and postoperative urine with a cost-effective 127-gene panel enables the characterization of tumor mutations. These findings provide cumulative evidence in support of the results of previous studies that testing urine for mutations is a useful strategy to complement the clinical management of bladder cancer patients. ABSTRACT: The standard diagnostic and follow-up examination for bladder cancer is diagnostic cystoscopy, an invasive test that requires compliance for a long period. Urine cytology and recent biomarkers come short of replacing cystoscopy. Urine liquid biopsy promises to solve this problem and potentially allows early detection, evaluation of treatment efficacy, and surveillance. A previous study reached 52–68% sensitivity using small-panel sequencing but could increase sensitivity to 68–83% by adding aneuploidy and promoter mutation detection. Here, we explore whether a large 127-gene panel alone is sufficient to detect tumor mutations in urine from bladder cancer patients. We recruited twelve bladder cancer patients, obtained preoperative and postoperative urine samples, and successfully analyzed samples from eleven patients. In ten patients, we found at least one mutation in bladder-cancer-associated genes, i.e., a promising sensitivity of 91%. In total, we identified 114 variants, of which 90 were predicted as nonbenign, 30% were associated with cancer, and 13% were actionable according to the CIViC database. Sanger sequencing of the patients’ formalin-fixed, paraffin-embedded (FFPE) tumor tissues confirmed the findings. We concluded that incorporating urine liquid biopsy is a promising strategy in the management of bladder cancer patients.