Development of a 90-minute integrated non-invasive urinary assay for bladder cancer detection

Despite suboptimal sensitivity, urine cytology is often performed as an adjunct to cystoscopy for bladder cancer diagnosis. We aimed to develop a non-invasive, fast molecular diagnostic test for bladder cancer detection with better sensitivity than urine cytology while maintaining adequate specificity.

Urine specimens were collected at 18 multinational sites from subjects prior to cystoscopy or tumor resection, and from healthy and other control subjects without evidence of bladder cancer. The levels of ten urinary mRNAs were measured in a training cohort (n=483) and regression analysis was used to identify a five mRNA model to predict cancer status. Performance of the investigational use only-labeled GeneXpert® (Cepheid, Sunnyvale, CA) Bladder Cancer Assay, an assay for detection of the five mRNAs (ABL1, CRH, IGF2, ANXA10, and UPK1B), was evaluated in an independent test cohort (n=450).

In the independent test cohort, the GeneXpert assay ROC curve AUC was 0.87 (95% CI: 0.81-0.92). At an example cut point of 0.4, the overall sensitivity was 73%, and the specificity was 90% and 77% for hematuria and surveillance patient populations, respectively.

We have developed a 90 minute, simple to perform urine-based test for the detection of bladder cancer that can that can help guide physician decision making in the management of bladder cancer. Additional evaluation in a prospective study is needed to establish clinical utility of this assay.

The Journal of urology. 2017 Oct 20 [Epub ahead of print]

Ellen Wallace, Russell Higuchi, Malini Satya, Leena McCann, Mandy Ly Sin, Julia A Bridge, Huilin Wei, Jun Zhang, Edith Wong, Andrew Hiar, Kathleen E Mach, Douglas Scherr, R Blair Egerdie, Shoichiro Ohta, Wade J Sexton, Maxwell V Meng, Alon Z Weizer, Michael Woods, G Kenneth Jansz, Joseph Zadra, Yair Lotan, Joseph C Liao

Cepheid, Sunnyvale, California. Electronic address: ., Cepheid, Sunnyvale, California., Department of Urology, Stanford University School of Medicine, Stanford, California and VA Palo Alto Health Care System, Palo Alto, California., Department of Pathology & Microbiology, University of Nebraska Medical Center, Omaha, Nebraska., Weill Cornell Medical College, New York, New York., Urology Associates / Urologic Medical Research, Kitchener, Ontario, Canada., Kan-Etsu Hospital, Saitama, Japan., Moffitt Cancer Center, Tampa, Florida., University of California San Francisco, San Francisco, California., University of Michigan, Ann Arbor, Michigan., University of North Carolina, Chapel Hill, North Carolina., Jansz MD, Burlington, Ontario, Canada., Male/Female Health and Research Centre, Barrie, Ontario, Canada., University of Texas Southwestern, Dallas, Texas.