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Liquid biopsy biomarker could revolutionize bladder cancer diagnostics and treatment

Researchers have developed a potential tumour DNA diagnostic test to better inform decision-making for bladder cancer treatment.
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Liquid biopsies that examine circulating tumour DNA (ctDNA) could be a game changer in aggressive bladder cancer diagnostics, according to the findings of a new study led by Dr. Alexander Wyatt, scientist with the Genome Sciences Centre at BC Cancer, researcher at the Vancouver Coastal Health Research Institute and assistant professor in the Vancouver Prostate Centre. The study was published in Nature Communications in January 2021.

The discovery is the first step towards validating a tool to improve treatment outcomes for the most severely ill of the roughly 1,730 British Columbians who were newly diagnosed with bladder cancer in 2020.

“Our study results offer a paradigm shift in the way we diagnose bladder cancer,” said Wyatt.

ctDNA is cell-free DNA released from cancer cells in the body. Previous studies have shown that this potential biomarker acts as a barometer of cancer severity—the higher ctDNA concentrations found in a single blood draw, the greater the amount of cancer present in a patient’s body.

Dr. Alexander Wyatt (photo courtesy of Vancouver Coastal Health Research Institute)

In collaboration with BC Cancer medical oncologist Dr. Bernhard Eigl and co-authors, Wyatt examined the ctDNA of over 100 patients with metastatic bladder cancer, which occurs when the disease progresses and the cancer spreads to areas of the body beyond the bladder. This later-stage and more dangerous disease requires time-sensitive decisions about treatment courses.

“For metastatic disease, chemotherapy used to be the only option,” says Wyatt. “There are now three or four alternative therapies for which patients are eligible, but clinicians cannot necessarily access the most up-to-date information on their patient’s disease to help decide what therapy to use.”

This is because it’s not typically possible to sample metastases in real time, so they have to rely on biopsies or surgical tissue that may have been collected years ago, and may not be representative of their current disease.

ctDNA could be the new gold standard in diagnostics

The current gold standard approach to obtain information about a person’s cancer is a tissue sample surgically removed from the tumour, however a liquid biopsy is less invasive and a more efficient way to collect information on the tumour. For those who live in remote or rural communities, the blood sample can be taken locally and sent to a lab for processing with results coming back in a matter of days.

“As we look to the future, we need to get information in real-time and have diagnostics that are representative of the present state of the disease. This is where the blood sample can really help us avoid subjecting patients to additional procedures or relying on tissue that was taken at an earlier time.”

The ctDNA blood draw could help clinicians decide whether to stick with chemotherapy as a treatment course, apply immunotherapies or use therapies that target specific genomic mutations.

“Circulating tumour DNA could add an extra layer of information about the genomic alterations in the tumour and disease severity, which will support an even more precise application of treatment.”

Liquid biopsies can also reveal treatment effectiveness in the event that ctDNA concentrations level off or decrease.

“We still need to conduct additional studies to test whether ctDNA data is indeed clinically useful and can be applied to clinical practices,” says Wyatt. “Next, we aim to validate in clinical trials whether or not ctDNA profiling is a reliable tool that matches or exceeds the current gold standard of tissue profiling.”

A version of this story was originally published on the Vancouver Coastal Health Research Institute website.

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