Genomic Alterations in Liquid Biopsies from Patients with Bladder Cancer

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Background: At least half of the patients diagnosed with non–muscle-invasive bladder
cancer (NMIBC) experience recurrence and approximately 15% will develop progression to
muscle invasive or metastatic disease. Biomarkers for disease surveillance are urgently
needed.
Objective: Development of assays for surveillance using genomic variants in cell-free
tumour DNA from plasma and urine.
Design, setting, and participants: Retrospective pilot study of 377 samples from 12 patients
with recurrent or progressive/metastatic disease. Three next-generation sequencing methods
were applied and somatic variants in DNA from tumour, plasma, and urine were
subsequently monitored by personalised assays using droplet digital polymerase chain
reaction (ddPCR). Samples were collected from 1994 to 2015, with up to 20 yr of follow-up.
Outcome measurements and statistical analysis: Progression to muscle-invasive or metastatic
bladder cancer; t test for ddPCR data.
Results and limitations: We developed from one to six personalised assays per patient.
Patients with progressive disease showed significantly higher levels of tumour DNA in
plasma and urine before disease progression, compared with patients with recurrent disease
(p = 0.032 and 1.3 106, respectively). Interestingly, tumour DNA was detected in plasma
and urine in patients with noninvasive disease, being no longer detectable in disease-free
patients. A significant level of heterogeneity was observed for each patient; this could be due
to tumour heterogeneity or assay performance.
Conclusions: Cell-free tumour DNA can be detected in plasma and urine, even in patients
with noninvasive disease, with high levels of tumour DNA detectable before progression,
especially in urine samples. Personalised assays of genomic variants may be useful for
disease monitoring.
Patient summary: Tumour DNA can be detected in blood and urine in early and advanced
stages of bladder cancer. Measurement of these highly tumour-specific biomarkers may
represent a novel diagnostic tool to indicate the presence of residual disease or to discover
aggressive forms of bladder cancer early in the disease course.
Original languageEnglish
JournalEuropean Urology
ISSN0302-2838
DOIs
Publication statusPublished - 21 Jan 2016

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