The study authors developed a low-coverage whole-genome sequencing technique, called “Urine Exfoliated Cells Copy Number Aberration Detector” (UroCAD), to detect copy number variants in urine-exfoliated cells.
The team then tested whether UroCAD could detect urothelial carcinomas in a single-blinded trial.
Shuxiong Zeng, MD, PhD, of Naval Medical University, Shanghai, China, and colleagues described this work in Clinical Cancer Research.
Study details and results
The researchers first tested UroCAD on urine samples from a discovery cohort of 190 patients – 126 with urothelial carcinoma and 64 noncancer controls. In this group, UroCAD detected urothelial carcinoma with a sensitivity of 82.5% and a specificity of 96.9%.
The researchers also analyzed samples from a validation cohort of 95 patients – 56 with urothelial carcinoma and 39 noncancer controls.
In this cohort, UroCAD had significantly higher sensitivity than urine cytology (80.4% and 33.9%, respectively; P < .001) but similar specificity (94.9% and 100%, respectively; P = .49) for the detection of urothelial carcinoma.
Among seven patients with pTa tumors, UroCAD had a sensitivity of 71.4%, while urine cytology had a sensitivity of 0%.
UroCAD’s sensitivity was greater for high-grade than low-grade urothelial carcinomas (86.7% and 60.0%, respectively). The assay was also more sensitive for larger tumors, with sensitivities of 66.7% for tumors measuring 1 cm or less, 72% for tumors between 1 cm and 3 cm, and 95.5% for tumors larger than 3 cm.
“The relatively lower sensitivity of UroCAD for the detection of lower-grade or smaller tumors is not unexpected, as these tumors are less likely to have abundant chromosomal alterations,” study author Chuan-Liang Xu, MD, PhD, of the Changhai Hospital in Shanghai, explained in a press release. “Ultimately, we believe that our assay could help to reduce the frequency of cystoscopy examination but not to replace it.”
The researchers noted that UroCAD positivity was associated with microscopic epithelial cells in cancer patients, and this suggests that insufficient exfoliative cells “might be the major technique limitation.”
Conclusions and next steps
“In summary, UroCAD could be a highly specific, robust, and noninvasive urothelial carcinoma diagnostic method with improved sensitivity and similar specificity as compared with cytology tests,” the researchers concluded.
“Within the next 5 years, we can see UroCAD in a variety of commercial formats available to the global markets, including the USA,” Dr. Xu commented in an interview. “We see UroCAD as a disruptive technology in diagnosing and monitoring patients with urothelial carcinoma.
“In America, given the COVID-19 pandemic, we also envision UroCAD becoming commercially available in the form of a mailed, at-home collection kit for high-risk patients, which may also be purchased off the shelf at commercial pharmacies,” Dr. Xu added. “We hope UroCAD will make a positive clinical impact to the urology field.”
In a follow-up trial (NCT04432909), researchers are evaluating the utility of UroCAD in the surveillance of urothelial carcinoma.
The current research was supported by various funding sources in China. The authors reported having no conflicts of interest.
SOURCE: Zeng S et al. Clin Cancer Res. 2020 Oct 9. doi: 10.1158/1078-0432.CCR-20-0401.
