EAU 2018: Prospective validation of a diagnostic urine test for bladder cancer: The HEMAturia study

Copenhagen, Denmark (UroToday.com) Kim E.M. van Kessel presented on an extremely exciting validation study of a urine-based diagnostic assay for bladder cancer: The HEMAturia study. The authors have previously published their findings on this test using a discovery cohort and retrospective validation cohort, reporting >90% sensitivity and 83-85% specificity. Now, they prospectively identified 968 patients referred to Urology for microscopic or macroscopic hematuria in 6 hospitals in the Netherlands. The urine sample was collected prior to undergoing diagnostic cystoscopy.

The test identifies 3 mutations (FGFR3, TERT, HRAS) and 3 methylations (OTX1, ONECUT2, TWIST1) from urine samples with volumes as low as 2ml in some patients within their study cohort. 52.7% of patients presented with macroscopic hematuria, and 45.6% presented with microscopic hematuria. Out of 968 patients, 116 patients were diagnosed with bladder cancer. The assay resulted in an AUC of 0.94, with 88% sensitivity (90% sensitivity for high grade disease) and 89% specificity. Negative predictive value was 98.5%. Only one false positive was found, which turned out to be invasive colorectal carcinoma into the bladder. Per the author, the test was quite specific to bladder carcinoma, since several known prostate and kidney cancers were not found to be positive with this assay.

These results are truly remarkable, and even more convincing based on the results of such a large prospectively collected cohort. The assay will now be developed for clinical use, and is being developed commercially by MDxHealth, Inc.

The development of such an assay has long been a dream for clinicians who see large volumes of hematuria patients. The current standard of care, which includes axial imaging, cystoscopy, and urine cytology for some patients, is costly, time-consuming, and not 100% diagnostic. Having a urine-based biomarker test to select which patients should undergo more intensive testing is a potential game-changer for our field. In this study alone, nearly 88% of patients might have been spared cystoscopic evaluation if the biomarker test were used as an initial screening tool.

Of course, the test still needs to be proven in the screening role, but it is likely that it will play an important role in future hematuria algorithms. Surely, this test will also be studied for use in patients under bladder cancer surveillance and potentially to even evaluate patients after neoadjuvant chemotherapy to assess the need for radical cystectomy (identifying T0 patients).

I look forward to having this test become clinically available, as I am sure it will have tremendous clinical and cost-saving implications for our field!

Speaker: Kim E.M. Van Kessel

Written by: Shreyas Joshi, MD, Fox Chase Cancer Center, Philadelphia, PA, Twitter: @ssjoshimd, at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark