Detecting Bladder Cancer Using a Urine-based Liquid Biopsy Test
A new study reports that an inexpensive way to analyze DNA isolated from cells in urine is more sensitive than urine cytology, a microscopic examination of cells in the urine.
When a doctor suspects a patient may have urothelial carcinoma –bladder cancer – she may order a test called urine cytology to determine if a tumor is present or not. In this test, cells present in a urine sample are examined under a microscope to look for signs of cancer.
While urine cytology has high specificity – meaning that it is a good test to rule out a diagnosis of cancer – it has low sensitivity, meaning it is likely to miss some cancers. Other, more sensitive, tests are more expensive or invasive, and doctors would like to have a sensitive but inexpensive and non-invasive test.
Scientists in China reported recently in Clinical Cancer Research, a journal of the American Association for Cancer Research (AACR), that a urine-based liquid biopsy test may provide a solution.
Called UroCAD, the test examines DNA isolated from cells in a urine sample and looks for copy number variations (CNVs), which are structural variations in the DNA where portions of the genome are repeated or deleted. Having a high number of CNVs has been linked to many forms of cancer.
“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,” said Jia-Tao Ji, MD, PhD, urologist at Shanghai Hudong Hospital. “Because CNVs are a hallmark of many cancers, we developed an assay to detect CNV burden in the DNA from urine exfoliated cells.”
After the researchers developed UroCAD, they validated the test in 95 patients, 56 of whom had bladder cancer and 39 did not have cancer. Compared with urine cytology, UroCAD was significantly more sensitive (roughly 80 percent versus roughly 34 percent) with a similar specificity (roughly 95 percent versus 100 percent).
The sensitivity of UroCAD corresponded to the grade of the tumor, detecting low-grade urothelial carcinoma with a sensitivity of 60 percent and high-grade tumors at 86.6 percent. The sensitivity also correlated with tumor size, more successfully detecting the larger tumors.
“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,” said Xu. “Ultimately, we believe that our assay could help to reduce the frequency of cystoscopy examination, but not to replace it.”