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Whole-Genome Sequencing Via Urine: Novel Modality for Detecting Urothelial Carcinoma

By: Celeste L. Dixon
Posted: Friday, October 30, 2020

A noninvasive, low-cost test that relies on urine-exfoliated cell DNA may detect chromosomal aberrations associated with urothelial carcinomas. The whole-genome sequencing technology, a customized bioinformatics workflow called UroCAD, was reported to have better sensitivity than cytology tests and similar specificity, according to Chuan-Liang Xu, MD, PhD, of Changhai Hospital, Shanghai, China, and colleagues. Their study findings were published in Clinical Cancer Research.

If clinical trials confirm these early study findings, UroCAD—urine-exfoliated cells copy number aberration detector—may reduce patients' burden by lessening the need for a cystoscopy to diagnose urothelial carcinoma and check for its recurrence. UroCAD was created by incorporating the many autosomal chromosomal changes discovered when comparing urine samples from 126 patients with urothelial carcinomas with those from 64 healthy controls.

In the external validation cohort, which included 95 participants (56 with urothelial carcinomas, 39 without), the novel assay identified the tumors with an overall sensitivity of 80.4%, a specificity of 94.9%, and an AUC of 0.91. Compared with cytology tests, the assay had significantly improved sensitivity (80.4% vs. 33.9%; P < .001) and comparable specificity (94.9% vs. 100%; P = .49).

Not surprisingly, said Dr. Xu in an American Association for Cancer Research press release, the sensitivity of the test correlated with tumor size: For detecting tumors of up to 1 cm, between 1 and 3 cm, and greater than 3 cm, UroCAD’s sensitivity was 66.7%, 72.0%, and 95.5%, respectively. Smaller and lower-grade tumors tend to be “less likely to have abundant chromosomal alterations,” noted Dr. Xu. “Ultimately, we believe our assay could help to reduce the frequency of cystoscopy examination, but not replace it.”

Disclosure: The study authors reported no conflicts of interest.



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