Cytology vs. biomarkers
Voided urine cytology has been the mainstay for urine-based bladder cancer detection, and it has the advantage of having very high specificity.
“If the cytology comes back positive, then there is a greater than 90% chance that cancer is present. However, a negative result is not that helpful because the majority of low-grade tumors have negative cytology, and that limitation of cytology is the gap that the newer biomarkers are trying to fill,” said Dr. Konety, professor and chair of urology at the University of Minnesota, Minneapolis.
As another drawback, there is a turnaround delay of several days for cytology, whereas some of the other biomarkers (BTA stat, NMP22BladderChek) are point-of-care tests that generate immediate results. In addition, the results of cytology can be variable because there are at least five official values for the results, and the interpretation is reader dependent. In contrast, some of the second- and third-generation biomarker tests provide a result that is cut and dry—the test is either positive or negative.
Consistent with the AUA/SUO guideline, Dr. Konety observed that the biomarkers seem to be finding the greatest application in the follow-up of patients diagnosed with bladder cancer and particularly as a second-level test in the setting of atypical urine cytology. It appears they are being used less often for initial diagnosis in patients with hematuria.
In order to investigate the uptake of the newer urinary biomarker tests for bladder cancer surveillance, Dr. Konety and colleagues conducted an analysis using Medicare data. Their methods did not include analyses of any individual assays, but the results showed that overall use of biomarkers by urologists increased from 11% in 2000 to 26% in 2011.
Commenting on the findings, Dr. Konety described the uptake as “stagnated” and said he does not believe that the new urinary markers have led to a change in approach to management of bladder cancer.
“The lament of people who have been doing research with the new urinary biomarkers is that these diagnostic tools have not been adopted to the extent that might be expected considering their specificity is in the 50% to 80% range. This reluctance is difficult to reconcile when juxtaposed against the high reliance on PSA for prostate cancer screening and monitoring, taking into account that as a stand-alone marker, PSA has a specificity of only about 25%,” Dr. Konety said.
He suggested multiple factors to explain the limited utilization of the bladder cancer biomarkers.
“Cost may be an issue, although the protein-based markers are covered by insurance and not that expensive, which may explain why the qualitative NMP22 assay may have the greatest use overall. And while the FISH assay was initially very expensive, costing thousands of dollars, it has now come down in price,” he said.
Logistics is another consideration, but uncertainty of how to apply the results clinically likely plays a major role.
“Because guidelines have not definitively advocated for or against biomarkers for diagnosis or surveillance, urologists have not been compelled to use them. In fact, the current AUA guideline on diagnosis, evaluation, and follow-up of asymptomatic microhematuria in adults, which is from 2012, doesn’t even advocate for cytology in the workup. That creates a high bar for justifying the use of these newer, more expensive markers,” Dr. Konety said.