Highly Sensitive Urine Test Could Be a Better, Less Invasive Tool for Bladder Cancer

A newly developed, highly sensitive urine test may be better at diagnosing and monitoring bladder cancer than the standard tests currently available to patients, according to study findings published in Cancer Discovery.

Researchers at Stanford School of Medicine in California developed the test that looks for fragments of cancer DNA in urine samples through a method called cancer personalized profiling by deep sequencing (CAPP-Seq), which tests for tiny bits of genetic material that cancer cells release as tumors grow.

“In the case of bladder cancer, the tumors are in direct contact with urine, and so, therefore, we hypothesized that there would be significant levels of tumor DNA present in the urine,” Maximilian Diehn, M.D., Ph.D., associate professor of radiation oncology, said in an interview with CURE. “Importantly, we were looking for pieces of the DNA not inside cancer cells and, in that way, it’s very different from what is currently done in clinic.”

The newly developed test looks at molecules that can’t be viewed under a microscope compared with the current cytology test that looks for abnormal cells in a patient’s urine. A cystoscopy is another test used for bladder cancer surveillance. The procedure involves using a hollow tube equipped with a lens to examine the lining of a person’s bladder and the urethra. However, the researchers noted, cystoscopy is an invasive procedure and cytology has suboptimal sensitivity. “The reason we wanted to develop this test even though there already is a test is because cytology is unfortunately not very sensitive,” Diehn said. “The sensitivity is only about 15 to 40 percent, so we wanted to develop a test that does better than that.”

They applied the CAPP-Seq method to two groups of patients. One was made up of 67 patients who had urine collected before treatment. This group mimicked how the test would behave in the case of screening or early detection, Diehn explained. The second group consisted of 118 patients with early-stage bladder cancer who had already been treated for the disease and their urine was collected during surveillance. The researchers found the test could detect cancer in its early stages of development, when it’s easier to treat.

The test correctly identified bladder cancer in 83 percent of patients with early-stage disease compared with 14 percent for the cytology test. In the surveillance group, the test correctly identified the disease in more than 90 percent of patients. In addition, researchers were able to detect bladder cancer recurrence an average of 2.7 months earlier than with cystoscopy. It also detected a median of six mutations per patient — some that could be potentially used as a biomarker for bladder cancer.

“We look for particular mutations that we know are often present in bladder cancer in the DNA that is floating in a patient’s urine,” Diehn said. “That way we can differentiate between a healthy urine sample and a urine sample from a patient with bladder cancer when we see mutations that are often seen in bladder cancer (and are) strongly predictive that that patient has a tumor in their bladder.”

Bladder cancer is the sixth most common cancer in the United States. Each year, more than 80,000 new cases of the disease are diagnosed, according to the American Cancer Society, and it appears more commonly in men.

Although the test is not yet clinically available, Diehn is excited that it outperformed the standard of care and hopes it will help patients down the road. “There is some more work needed so that we can get it into routine clinical care,” he said. “We will want to reproduce our results and then do a prospective study where we do the test and then manage patients based on those results.”