Bladder Care Epigenetic Test Allows The Sensitive Early Detection Of Bladder Cancer From Urine Samples

Introduction: Bladder cancer (BC) is the 5th most common cancer in the USA, with 81,190 new cases and 17,240 deaths in 2018. The high recurrence rate of BC requires a lifelong patient follow-up with cystoscopy. However, the invasiveness of cystoscopy and the high costs associated to this procedure, poses a significant burden on patients as well as on the healthcare system. Several tests for the non-invasive detection of BC have been developed in the past years however, because of relatively low sensitivities and/or specificities (especially for low-grade tumors), these tests have not been adopted for the routine clinical use. Therefore, a non-invasive, simple and sensitive test for detection and routine monitoring of BC is needed. Methods: Bladder CARE is a new non-invasive and quantitative test that measures the methylation levels of three BC specific biomarkers and two internal controls in urine samples. Contrary to other epigenetic tests, Bladder CARE analyzes DNA methylation without converting the DNA with sodium bisulfite, thus minimizing the degradation of the target DNA. In this clinical study, we evaluated the performance of this test using voided urine samples collected from 136 healthy individuals and 77 BC patients with no prior history of bladder cancer. Urine specimens were collected and stabilized using Bladder CARE at-home urine sample collection kit and BC detection was performed by a CLIA-certified and CAP-accredited laboratory (Pangea Laboratory LLC) using Bladder CARE. The results were then compared to the clinical information (cystoscopy). Additionally, the test linearity and limit of detection (LOD) were determined by analyzing artificial samples with Bladder CARE test. Results: Bladder CARE was able to discriminate BC from healthy control samples with a sensitivity of 93.5%, a specificity of 92.6%, and a positive and negative predictive value of 87.8% and 96.2%, respectively. Remarkably, low-grade tumors were detected with a sensitivity of 90.0%. We also found that Bladder CARE test has a LOD of 0.046% (the equivalent of detecting 1 cancer cell in a sample containing 2,200 normal cells). Conclusions: While cystoscopy remains the gold standard to confirm the presence of BC, the superior sensitivity of Bladder CARE test, together with its low LOD, make this test an effective early indicator of low-grade tumors and for routine recurrence monitoring of BC patients. In addition, Bladder CARE urine collection kit allows to collect and stabilize the urine specimen comfortably at-home and mail it to the testing laboratory at room temperature, streamlining the patients9 detection and monitoring process. Citation Format: Paolo Piatti, Michiko Suwoto, Taikun Jamada, Yap Ching Chew, Gangning Liang, Saum Ghodossipour, Siamak Daneshmand, Xi-Yu Jia. Bladder care epigenetic test allows the sensitive early detection of bladder cancer from urine samples [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2295.