New bladder cancer test to launch in 2022

Liquid biopsy provider Nonacus has partnered with the University of Birmingham to develop a non-invasive test for bladder cancer, which is expected to be available by mid-2022.

The test will use Nonacus’ liquid biopsy technology, and a panel of biomarkers validated by Dr Rik Bryan and Dr Douglas Ward from the University’s Bladder Cancer Research Centre, to diagnose the disease from urine samples.

In the UK, over 100,000 people a year are referred to hospital clinics that investigate for bladder cancer, usually after passing blood in their urine (haematuria). The first stage of investigation is usually cystoscopy, which involves inserting a camera into the bladder. Around 12% are subsequently diagnosed with bladder cancer, normally after a second invasive procedure to extract a biopsy.

Dr Bryan, director of the Bladder Cancer Research Centre, said: “While blood visible in the urine should always be investigated, over 80% of people who have a cystoscopy at a haematuria clinic are diagnosed with non-malignant conditions or have no abnormality. Unfortunately, the remaining 20% will need a further invasive procedure to confirm diagnosis. What is required is a highly sensitive and specific, non-invasive test that can rapidly determine those who need a biopsy and those who do not, and a urine test is the obvious place to start.”

While the ‘liquid biopsy’ approach is attractive, the low levels of tumour DNA in a background of DNA from normal tissues requires highly sensitive analytical techniques to obtain accurate results. However, researchers at the University started their work knowing that Nonacus has pioneered commercial non-invasive prenatal tests to identify low-levels of fetal DNA in maternal blood samples.

The researchers used ‘deep sequencing’ of tumour DNA to identify mutations that are present in the majority of urothelial bladder cancers (UBCs). Their work, funded by Cancer Research UK and an MRC Confidence in Concept grant, involved sequencing 23 genes from tumour samples collected from 956 newly diagnosed, treatment-naïve patients. This deep sequencing of genes identified 451 unique mutations that were present in over 96% of tumours. The mutations were identifiable in urine samples collected at the same time as tumour sampling.

Mutated DNA in a urine sample can be extracted from cancer cells shed into the urine from the lining of the urinary tract, or can be found as cell-free DNA fragments. However, extracting DNA from the cancer cells provides more reliable amounts of DNA for the test, especially when only small volumes of urine may be available. Coupling the mutation panel with the molecular identifiers and the target capture technology provided by the Nonacus Cell3 Target can provide a more sensitive test than the PCR-based approach.

The original research also determined the influence of the mutations on cancer progression, time to recurrence, and overall and disease-specific survival in patients with non-muscle-invasive bladder cancer (NMIBC), and disease-specific survival in patients with muscle-invasive bladder cancer (MIBC), raising the possibility that the test could be used to stratify patients according to risk.