Urine test may revolutionize bladder cancer detection
A novel urine test may detect bladder cancer earlier than available methods, according to study results published in Cancer Discovery.
Maximilian Diehn, MD, PhD, associate professor of radiation oncology at Stanford University, and colleagues developed a high-throughput sequencing-based hybrid capture method for urine tumor DNA detection.
They speculated that the approach — called uCAPP-Seq — would be superior to cytology for detection of early-stage bladder cancer and posttreatment residual disease.
Diehn and colleagues assessed their approach in a study of 67 healthy adults and 118 patients with early-stage bladder cancer who either had urine collected prior to treatment or during surveillance.
The method detected tumor DNA in 84% of cases when using an approach blinded to tumor mutation status and 93% of cases using a tumor mutation-informed approach. Researchers reported specificity of 96% to 100%.
During surveillance, investigators detected tumor DNA in 91% of patients who recurred, and detection preceded clinical progression in 92% of cases.
“Detecting bladder cancer DNA in urine appears to be an extremely promising approach for both early detection and surveillance of bladder cancer,” Diehn told HemOnc Today. “Our findings suggest that this approach should also be explored for other cancers affecting the urinary tract.”
HemOnc Today spoke with Diehn about his team’s research, the benefit of urine-based tests compared with other bladder cancer detection methods, and the likelihood that this approach could become widely adopted.
Question: What prompted this study?
Answer: We previously developed a method called CAPP-Seq, which is an ultra-sensitive and -specific method for detecting tumor DNA in the blood. In prior work we applied CAPP-Seq to a variety of malignancies, including lymphoma, lung cancer and esophageal cancer.
Our new study is related to our prior research, but because we were studying early-stage bladder cancer, we focused on detecting tumor DNA in urine rather than blood. We thought this likely would work well because bladder tumors are in direct contact with urine.
Bladder cancer is the sixth most common cancer type, and we don’t have efficient, noninvasive methods for detecting it or monitoring response after treatment. Cystoscopy is standard, but that is invasive, uncomfortable and costly. There is a major unmet need for noninvasive tests that can minimize the number of cystoscopy procedures performed.
Q: How did you conduct this study?
A: First, we developed a novel method to detect urine tumor DNA. This method is based on CAPP-Seq, which measures cell-free tumor DNA released from dead tumor cells into the blood. However, we had to modify it significantly to be able to detect bladder tumor DNA in urine efficiently.
We began by optimizing a method for purifying cell-free DNA from the urine. We then optimized the sequencing approach that we use to detect the presence of bladder cancer DNA in cell-free urine DNA. These optimizations make up a new method called urine tumor DNA CAPP-Seq (uCAPP-Seq).
We applied this method to two patient cohorts. For the first cohort, we collected urine samples at the time of diagnosis to mimic a cancer early detection or screening application. The second cohort had been previously treated for bladder cancer and were in the surveillance setting. We wanted to see if we could detect or predict recurrence of cancer solely through a urine sample and compared our approach to cystoscopy and cytology.
Q: What did you find?
A: The results were quite striking. We were able to detect tumor DNA in 83% of patients at 97% specificity, which is a dramatic improvement compared with the urine cytology test. The mutations that we see in urine very closely matched the mutations that can be found by removing the tumor surgically and analyzing it. Results were even better in the second cohort. We were able to detect recurrence with 91% sensitivity and 100% specificity. We detected recurrence from a single urine sample often multiple months before clinical diagnosis. Given how striking the results are, we’re hopeful that there will be clinical utility to developing such an approach for routine use.
Q: When might this approach become widely adopted?
A: The key consideration when detecting cancer using these kinds of tumor DNA-based approaches is determining what cancer you are trying to detect. From there, you can decide which might be the best bodily fluid to use. Blood makes sense for a variety of cancers, but for cancers that affect the genitourinary system, urine is a potentially ideal fluid because it is in such close contact with the tumor. Before clinical adoption, prospective studies demonstrating the clinical utility of this approach will need to be conducted. Such prospective studies should focus on using this biomarker to make changes in patient management. For example, one could envision a study in which patients in the surveillance setting receive the test prospectively to see if there would be survival improvements based on early intervention or cost savings compared with existing methods. – by Joe Gramigna
Dudley JC, et al. Cancer Discov. 2018;doi:10.1158/2159-8290.CD-18-0825.
For more information:
Maximilian Diehn, MD, PhD, can be reached at Stanford Medicine, Department of Radiation Oncology, 875 Blake Wilbur Drive, MC-5847, Stanford, CA 94305; email: firstname.lastname@example.org.
Disclosure: Diehn reports being a co-inventor on patent applications related to CAPP-Seq.