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UroCAD: Liquid Biopsy Outperforms Urine Cytology in Bladder Cancer Detection

UroCAD is a new, urine-based liquid biopsy test. A recent study published by the American Association for Cancer Research has reported UroCAD provides higher sensitivity and specificity when detecting urothelial carcinoma compared with urine cytology.

Urine cytology is a technique widely used to screen for bladder cancer. Whilst it provides high specificity, it lacks sensitivity, especially for cancers that are still in the early stages of development. Alternatively, cystoscopy is a more accurate procedure which looks inside the bladder using a narrow camera, called a cystoscope. However, it is highly invasive and can result in additional costs and complications for the patient. Thus, a novel, non-invasive and inexpensive test is desirable for the detection and monitoring of bladder cancer.

DNA can be isolated from urine-exfoliated cells. These are a complex mixture of cells, shed from the lining of the bladder and may potentially include tumour cells. Thus, they can provide clues to the presence of bladder cancer, even for low-grade cancers. DNA copy number variants (CNVs) are a hallmark of many cancers. A recent study developed a novel assay to detect the level of CNVs in the DNA of these urine exfoliated cells. 

Methods and Results

The assay, called UroCAD, begins with a simple urine sample. Once DNA has been extracted, it can be analysed using low-coverage whole-genome sequencing (LC-WGS). The assay aims to detect the overall CNV burden in this DNA, not specific genetic alterations. Therefore, the authors note that this is an ideal and highly cost-effective sampling analysis technique.

The study reported that UroCAD identified urothelial carcinoma with a sensitivity and specificity of 82.5% and 96.9%, respectively. It was also found to have significantly higher specificity and sensitivity when compared to urine cytology in the detection of urothelial carcinoma. Furthermore, in a subset of patients whose low-grade tumours were confined to the epithelial layer of the bladder, UroCAD has a sensitivity of 71.4%, whilst urine cytology had a sensitivity of 0%.

Limitations of UroCAD and Future Directions

One limitation of this assay is that the detection of the CNV burden was correlated with the number of epithelial cells present. Therefore, it is likely that a lack of sufficient exfoliated cells may limit the usefulness of the assay.

Similarly, the sensitivity of UroCAD corresponded with tumour grade and tumour size. For example, it could detect low-grade and high-grade urothelial carcinoma with a sensitivity of 60% and 86.6%, respectively. Furthermore, sensitivity for tumours of 1cm or less was 66.7% compared to 95.5% for tumours greater than 3cm.

The authors note that the lower sensitivity of UroCAD for lower-grade or smaller tumours is not unexpected. Often these tumours have less abundant chromosomal alterations, thus are less likely to be detected. Therefore, they suggest that UroCAD could be used to help reduce the need for repeated cystoscopy examinations, but not to replace them entirely. 

However, for patients with haematuria or those who have suspected urothelial carcinoma, UroCAD is a promising new test to replace cytology and reduce the need to cystoscopy examinations. The use of UroCAD for the surveillance of urothelial carcinoma is currently being evaluated in a clinical trial.

More on these topics

Cancer / Genetic Variants / Liquid Biopsy / WGS