Researchers develop urine test for bladder cancer

The researchers found that by testing for fragments of cancer DNA in urine, they could find the cancer in early stages of development, when it’s easier to treat.

Maximilian Diehn and Ash Alizadeh.
Mark Tuschman

Researchers at the School of Medicine have developed a highly sensitive urine test for diagnosing and monitoring bladder cancer. 

The test involves looking for fragments of cancer DNA in urine samples. “This study describes a new diagnostic approach to bladder cancer focused on analysis of urine samples,” said Maximilian Diehn, MD, PhD, associate professor of radiation oncology. “Urine is in direct contact with bladder tumors, which shed some of their DNA into it.”

The findings were published online Dec. 21 in Cancer Discovery. Diehn shares senior authorship with Ash Alizadeh, MD, PhD, associate professor of medicine. Postdoctoral scholars Jonathan Dudley, MD, and Joseph Schroers-Martin, MD, are the lead authors.

Sixth most common cancer

Bladder cancer is the sixth most common cancer. More than 80,000 people are diagnosed with it every year in the United States. Currently, the most accurate method of diagnosing bladder cancer is through cystoscopy, an invasive method to visualize the bladder and take tissue samples. Another method is to look for cancer cells in the urine via a cytology test. Although noninvasive, this approach has suboptimal sensitivity, Diehn said.

The research builds on earlier studies co-authored by Diehn and Alizedah in which they showed that they could detect certain cancers by looking for DNA fragments of tumors circulating in the bloodstream using a method called CAPP-Seq, an abbreviation for cancer personalized profiling by deep sequencing. In the new study, the researchers modified molecular and bioinformatics aspects of this technique to apply to bladder cancer DNA fragments found in urine. They analyzed a total of 67 healthy adults and 118 patients with early stage bladder cancer who either had urine collected prior to treatment or during surveillance.

The researchers found that by testing for bladder cancer in urine, they could detect cancer in the early stages of development, when it can be treated more easily. Their approach correctly identified the presence of bladder cancer in 83 percent of patients with early stage bladder cancer, compared with only 14 percent for the clinically available urine cytology test.

One of the greatest benefits of the new approach may be its ability to detect the recurrence of bladder cancer after someone has been treated for the disease. “In our test samples, we were able to detect bladder cancer recurrence an average of 2.7 months earlier than could be done with cystoscopy,” Alizadeh said. With the new approach, they detected almost all cases of recurrent bladder cancer, nearly double the sensitivity of cystoscopy and cytology. 

The researchers believe that the method of looking for cancer DNA in body fluids other than blood could be more widely applied. “It may eventually be useful for testing saliva for oral cancer, cerebrospinal fluid for neurological cancers or sputum for lung cancer,” Diehn said.

Other Stanford co-authors are associate professor of urology Joseph Liao, MD; clinical assistant professor in pathology Henning Stehr, MD; pathology resident Simon Chen, MD; urology affiliate Dharati Trivedi, MD; pathology instructor Helio Costa, PhD; postdoctoral scholars Mohammad Esfahani, PhD, Mandy Sin, PhD, and Barzin Nabet, PhD; former postdoctoral scholar Aadel Chaudhuri, MD, PhD; medical students William Shi and Daniel Lazzareschi; former graduate student Jacob Chabon, PhD; research associate Chih Long Liu, PhD; cytologist Harumi Lim; and cytopathology laboratory director Marumi Lim.

Alizadeh and Diehn are members of the Sthe Stanford Institute for Stem Cell Biology and Regenerative Medicine, the Stanford Cancer Institute and Stanford Bio-X.

This research was supported by the Stanford-National Institute of Standards and Technology Joint Initiative for Metrology in Biology, the Stanford Cancer Institute, the Albert Institute for Bladder Cancer Care and Research, the National Cancer Institute, the National Institutes of Health, the Virginia and D.K. Ludwig Fund for Cancer Research and the CRK Faculty Scholar Fund.

Stanford’s departments of Pathology, of Medicine and of Radiation Oncology also supported the work.



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