Urine-based liquid biopsy more effective than urine cytology in bladder cancer detection

The UroCAD urine-based liquid biopsy assay detected urothelial carcinoma with higher sensitivity and comparable specificity as urine cytology, according to findings from an observational trial published in Clinical Cancer Research.^1,2

The sensitivity rate for the detection of urothelial carcinoma exceeded 80% with UroCAD compared with just over 30% with urine cytology. The specificity rates were approximately 95% with versus 100%, respectively. The sensitivity of UroCAD corresponded with both tumor grade and tumor size.

“Urine cytology, which is widely used to screen for bladder cancer, has high specificity but lacks sensitivity, especially for low-grade cancers,” study author Chuan-Liang Xu, MD, PhD, a urologist at Changhai Hospital in Shanghai, stated in a press release. “Cystoscopy, while more accurate than cytology, is an invasive procedure with added costs and potential complications for the patient,” added Xu. “Therefore, an inexpensive, non-invasive test for the detection and monitoring of bladder cancer is an unmet clinical need.”

UroCAD works by analyzing DNA copy number variants (CNVs) in the urine exfoliated cells.

“The DNA isolated from urine exfoliated cells, a complex cell mixture that potentially includes tumor cells shed from the lining of the bladder, can provide clues to the presence of bladder cancer,” study author Jia-Tao Ji, MD, PhD, urologist at Shanghai Hudong Hospital, stated in the press release. “Because CNVs are a hallmark of many cancers, we developed an assay to detect CNV burden in the DNA from urine exfoliated cells.”

The discovery phase of the trial included 190 patients, comprising 64 cancer-free patients and 126 patients with urothelial carcinoma. Among the group of patients without cancer, the investigators did not detect any significant CNV burden. UroCAD detected urothelial carcinoma in this discovery cohort with an 82.5% rate of sensitivity and a 96.9% specificity rate, respectively.

The investigators then proceeded to compare the UroCAD assay with urine cytology in a 95-patient validation cohort. The validation cohort comprised 39 patients without cancer and 56 patients with urothelial carcinoma.

The results showed that UroCAD had significantly higher sensitivity for the identification of urothelial carcinoma at a rate of 80.4% versus 33.9% with urine cytology. Of note, among patients with pTa tumors (noninvasive papillary carcinoma), the sensitivity rates were 71.4% versus 0 percent, respectively. The specificity rates were comparable at 94.9% versus 100% with UroCAD versus urine cytology, respectively.

There was a positive correlation between the sensitivity of UroCAD and tumor grade, with the assay showing a sensitivity rate of 60% in detecting low-grade tumors and 86.6% in detecting high-grade tumors. There was also a positivity correlations between sensitivity and tumor size at 66.7% for detecting tumors ≤1 cm; 72% for tumors >1 cm and ≤3 cm; and 95.5% for tumors >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,” stated Xu. “Ultimately, we believe that our assay could help to reduce the frequency of cystoscopy examination, but not to replace it.”

Added Ji, “For patients with hematuria or who have suspected urothelial carcinoma, UroCAD is a promising way to replace cytology and to reduce repeated cystoscopy examinations.”

An ongoing clinical trial (NCT04432909)³ is further evaluating the accuracy of UroCAD in identifying urothelial carcinoma, and is also assessing the assay’s potential as a surveillance tool in follow-up assessment of patients with urothelial carcinoma. The prospective, multicenter, single-blinded study has a targeted enrollment of 500 patients and an estimated primary completion date of January 30, 2022.

In the press release, Xu noted that the efficacy of UroCAD may be limited when there is not enough exfoliated cells, as accurately assessing CNV burden is contingent on there being a sufficient amount of epithelial cells.

References

1. Urine-based Liquid Biopsy Test Outperforms Urine Cytology in Detecting Bladder Cancer. AACR. Posted October 9, 2020. Accessed October 9, 2020. https://bit.ly/2SGfgUy

2. Zeng S, Ying Y, Xing N, et al. Noninvasive detection of urothelial carcinoma by cost-effective low-coverage whole-genome sequencing from urine-exfoliated cell DNA. Clin Cancer Res [published online October 9, 2020]. doi: 10.1158/1078-0432.CCR-20-0401

3. A Prospective, Multi-centre, Single-blinded Study of UroCAD for Urothelial Carcinoma Diagnosis and Follow-up. ClinicalTrials.gov. Last updated June 16, 2016. Accessed October 9, 2020. https://clinicaltrials.gov/ct2/show/NCT04432909.