Cxbladder tests are urinary biomarker tests for detection of urothelial carcinoma (UC). We developed enhanced Cxbladder tests that incorporate DNA analysis of 6 single-nucleotide polymorphisms (SNPs) for the FGFR3 and TERT genes, in addition to the current 5 mRNA biomarkers and clinical risk factors.
Two multicenter, prospective studies were undertaken in: (1) US patients with gross hematuria aged ≥18 years, and (2) Singaporean patients with gross hematuria or microhematuria aged >21 years. All patients provided a midstream urine sample and underwent cystoscopy. Samples were retrospectively analyzed using enhanced Cxbladder-Triage (CxbT+; risk stratifies patients), Cxbladder-Detect (CxbD+; risk stratifies patients and detects positive patients) and the combination CxbT+×CxbD+.
In the pooled cohort (n = 804; gross hematuria: n = 484, microhematuria: n = 320), CxbD+ had a sensitivity of 97% (95% CI 89-100%), specificity of 90% (95% CI 88-92%), and negative predictive value of 99.7% (95% CI 99-100%) for detection of UC. Overall, 83% of patients were CxbD+-negative (ie, needed no further work-up). Of 133 CxbD+-positive patients, 59 had a confirmed tumor, of which 19 were low-grade non-invasive papillary carcinoma [Ta] or papillary urothelial neoplasm of low malignant potential. In total, 40 tumors were high-grade Ta, T1-T4, Tis, including concomitant carcinoma in situ. Of the 74 patients with normal cystoscopy, 41 were positive by SNP analysis. CxbT+ and CxbD+ had significantly better specificity than the first-generation Cxbladder tests (P<.001).
This study in ethnically diverse patients with hematuria showed the analytical validity of the enhanced Cxbladder tests.
The Journal of urology. 2022 Dec 30 [Epub ahead of print]
Yair Lotan, Jay D Raman, Badrinath Konety, Siamak Daneshmand, Florian Schroeck, Shahrokh F Shariat, Peter Black, Michel de Lange, Scott Asroff, Evan Goldfischer, Mitchell Efros, Kian Tai Chong, Eugene Huang, Hong Liang Chua, Qing Hui Wu, Siying Yeow, Weida Lau, Jin Yong, Molly Eng
University of Texas Southwestern, Dallas, Texas., Penn State Health Milton S. Hershey Medical Center, Hershey, Pennsylvania., Allina Health Cancer Institute, Minneapolis, Minnesota., Department of Urology, USC/Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California., White River Junction Veteran Affairs Medical Center, White River Junction, Vermont., Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria., Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia, Canada., Pacific Edge Ltd, Dunedin, New Zealand., New Jersey Urology, Mount Laurel Township, New Jersey., Premier Medical Group, Poughkeepsie, New York., Accumed Research Associates, Garden City, New York., Surgi-TEN Specialists, Farrer Park Hospital, Singapore., Department of Urogynaecology, KK Women's and Children's Hospital, Singapore., Department of Urology, National University Hospital, Singapore., Department of Urology, Khoo Teck Puat Hospital, Singapore., Department of Urology, Singapore General Hospital, Singapore.