Disclosures: Xu reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
November 23, 2020
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Noninvasive assay outperforms standard cytology in detection of urothelial carcinoma

Disclosures: Xu reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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A urine-based whole-genome sequencing assay demonstrated high specificity and comparable sensitivity to standard cytology for the detection of urothelial carcinoma, according to study results published in Clinical Cancer Research.

The Urine Exfoliated Cells Copy Number Aberration Detector (UroCAD) potentially could be used as a noninvasive approach for diagnosis of urothelial carcinoma and surveillance for recurrence before cystoscopy, researchers wrote.

A urine-based whole-genome sequencing assay demonstrated high specificity and comparable sensitivity to standard cytology for the detection of urothelial carcinoma.
A urine-based whole-genome sequencing assay demonstrated high specificity and comparable sensitivity to standard cytology for the detection of urothelial carcinoma.

“Traditional methods used to diagnose urothelial cancer include cystoscopy, CT urography and urine cytology. Patients with urothelial carcinoma usually have to undergo lifelong cystoscopy for surveillance, because it is a disease that recurs often,” Chuan-Liang Xu, MD, PhD, urologist at Changhai Hospital of Shanghai in China, told Healio. “However, cystoscopy is invasive and uncomfortable for patients, and costs a lot of money. CT urography is less accurate and exposes patients to radiation. Traditional urine cytology involves trying to find tumor cells in the urine, but this method could miss up to 50% to 70% of tumors. There is a great unmet need to establish a new noninvasive and more accurate method to detect urothelial cancer by analyzing the chromosomal alterations from urine-exfoliated cells and reduce the use of cystoscopy.”

Chuan-Liang Xu, MD, PhD
Chuan-Liang Xu

For this reason, Xu and colleagues developed the UroCAD assay, which analyzes urine samples with low-coverage whole-genome sequencing. Researchers examined the efficacy of the assay in the detection of chromosomal aberrations in urine samples of 126 patients with urothelial carcinoma and 64 nontumor disease samples.

Results of a diagnostic model that incorporated all autosomal chromosomal changes in urine-exfoliated cells showed UroCAD identified urothelial carcinoma with a sensitivity of 82.5% and specificity of 96.9%.

Researchers then assessed the assay in a validation cohort that included 56 patients with urothelial carcinoma and 39 individuals without cancer. The assay outperformed standard urine cytology with significant improvements in sensitivity (80.4% vs. 33.9%; P < .001) and comparable specificity (94.9% vs. 100%). Among seven patients with low-grade tumors confined to the epithelial layer of the bladder, UroCAD demonstrated significantly higher sensitivity than urine cytology (71.4% vs. 0%).

Moreover, the assay had a sensitivity of 60% for the detection of low-grade disease and 86.6% for the detection of high-grade disease. The sensitivity of the test correlated with tumor size, with a sensitivity of 66.7% in the detection of tumors of 1 cm or smaller, 72% for tumors between 1 cm to 3 cm and 95.5% for tumors greater than 3 cm.

“Frequent disease recurrence is a significant characteristic of urothelial cancer. After surgery, patients require frequent cystoscopy to assess for recurrence or residual disease,” Xu said. “Most guidelines recommend cystoscopy at 3-month intervals for 2 years, and lifelong surveillance every 6 months or once yearly. This causes pain and economic burden to patients and results in poor patient compliance.”

For patients with hematuria and suspected urothelial carcinoma, UroCAD could replace the cytology test and reduce the use of cystoscopy, Xu added.

“For those with suspected upper urinary tract urothelial carcinoma, UroCAD can guide imaging techniques and provide more information to urologists. Further research is needed to evaluate the efficacy of UroCAD in disease surveillance,” he told Healio. “We want to assess whether the assay can detect residual or recurrent tumor before cystoscopy, and to examine if the alteration burden of chromosomes is related to the prognosis of tumor. We have already initiated a multi-institutional and single-blind clinical trial to address these questions.”

For more information:

Chuan-Liang Xu, MD, PhD, can be reached at Changhai Hospital of Shanghai, Changhai Road 168, Yangpu District, Shanghai 200433, China; email: drxuchuanliang@126.com.