Detection of Cancer Mutations by Urine Liquid Biopsy as a Potential Tool in 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.

Recent development of urinary biomarkers for bladder cancer diagnosis and monitoring

“…In this study, authors recruited 12 BC patients and analysed the preoperative and postoperative urine samples of 11 patients. Indeed, depending on the presence of somatic mutations in BC‐related genes, the detection sensitivity of early screening can be increased to 91% 55 . These data reveal a rich mutational landscape in BC, and based on these features, somatic mutation can be developed into biomarkers, and become one of the promising strategies for the treatment of BC in the future.…”

“…Indeed, depending on the presence of somatic mutations in BC-related genes, the detection sensitivity of early screening can be increased to 91%. 55 These data reveal a rich mutational landscape in BC, and based on these features, somatic mutation can be developed into biomarkers, and become one of the promising strategies for the treatment of BC in the future. ctDNA from urine also has the ability to detect MRD in MIBC for diagnosis.…”

Urine-Based Biomarker Test Uromonitor® in the Detection and Disease Monitoring of Non-Muscle-Invasive Bladder Cancer—A Systematic Review and Meta-Analysis of Diagnostic Test Performance

“…Among urine-based diagnostic tests (UBDT), only urinary cytology is widely established in clinical practice, although it exhibits limited sensitivity in low-grade (LG) UCB and heavily relies on the expertise of the examiner [2]. Over the past two decades, several UBDTs have been developed in an effort to avoid unnecessary cystoscopies in the oncological follow-up of NMIBC patients without compromising patient safety [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17]. Cystoscopic follow-up, in particular, is associated with significant discomfort for NMIBC patients and significantly contributes to the high long-term costs of this disease [18].…”