Urine-DNA testing for bladder cancer may decrease the number of patients with gross hematuria who would need to undergo flexible cystoscopy, researchers concluded based on the findings of a prospective, blinded study.
Flexible cystoscopy, the current standard for detecting bladder tumors, is costly, invasive, and imperfect, the investigators, led by Per Guldberg, PhD, of the Danish Cancer Society Research Center in Copenhagen, noted.
The study included 475 patients who underwent standard urologic examination, including flexible cystoscopy and computed tomography urography, and provided urine samples immediately before (461 patients, 97.1%) and after (444 patients, 93.5%) cystoscopy. Researchers collected urine cells from full bladder voids using a filtration device containing an 8 µm pore size membrane filter and tested the cells for 8 DNA mutation and methylation biomarkers.
Clinical evaluation identified 99 patients (20.8%) with urothelial bladder tumors. Using this result as a reference and based on the analysis of all urine samples, the DNA test had a sensitivity of 97%, a specificity of 76.9%, a positive predictive value of 52.5%, and a negative predictive value of 99%, Dr Guldberg and colleagues reported online ahead of print in European Urology.
In 3 patients with a positive urine-DNA test without clinical evidence of cancer, a tumor was detected at repeat cystoscopy within 16 months, according to the researchers.
“In conclusion, with a negative predictive value of 99%, urine-DNA testing may be used to identify a large subgroup of patients with gross hematuria in whom the cystoscopic component of the work-up is not required,” the investigators wrote.
A positive DNA-test result was obtained for 1 or both urine samples in 96 of 99 patients with bladder tumors and 87 of 376 patients without clinical evidence of cancer. The specificity of the urine-DNA test was significantly greater for pre-cystoscopy compared with post-cystoscopy urine specimens (87.5% vs. 81.7%); the sensitivity did not differ significantly.
The filtration device used in the study was designed and patented by Dr Guldberg and a colleague, Kenneth E. Steven, MD. As described in a 2015 report in PLoS One, the device has a removable cartridge housing a membrane filter. After urinary cells are collected, the filter can be transferred to a storage unit containing an appropriate preserving solution.
“The practical use of urinary cell-based tests is often hampered by difficulties in handling and analyzing large sample volumes, the need for rapid sample processing to avoid degradation of cellular content, and low sensitivity due to a high background of normal cells,” the authors wrote.