Prospective Validation of an mRNA-based Urine Test for Surveillance of Patients with Bladder Cancer.

A fast, noninvasive test with high sensitivity (SN) and a negative predictive value (NPV), which is able to detect recurrences in bladder cancer (BC) patients, is needed. A newly developed urine assay, Xpert Bladder Cancer Monitor (Xpert), measures five mRNA targets (ABL1, CRH, IGF2, UPK1B, and ANXA10) that are frequently overexpressed in BC.

To validate Xpert characteristics in patients previously diagnosed with non-muscle-invasive BC.

Voided precystoscopy urine samples were prospectively collected at 22 sites. Xpert, cytology, and UroVysion were performed. If cystoscopy was suspicious for BC, a histologic examination was performed. Additionally, technical validation was performed and specificity was determined in patients without a history or clinical evidence of BC.

Test characteristics were calculated based on cystoscopy and histology results, and compared between Xpert, cytology, and UroVysion.

Of the eligible patients, 239 with a history of BC had results for all assays. The mean age was 71 yr; 190 patients were male, 53 never smoked, and 64% had previous intravesical immunotherapy (35%) or chemotherapy (29%). Forty-three cases of recurrences occurred. Xpert had overall SN of 74% (95% confidence interval [CI]: 60-85) and 83% (95% CI: 64-93) for high-grade (HG) tumors. The NPV was 93% (95% CI: 89-96) overall and 98% (95% CI: 94-99) for HG tumors. Specificity was 80% (95% CI: 73-85). Xpert SN and NPV were superior to those of cytology and UroVysion. Specificity in non-BC individuals (n=508) was 95% (95% CI: 93-97).

Xpert has an improved NPV compared with UroVysion and cytology in patients under follow-up for BC. It represents a promising tool for excluding BC in these patients, reducing the need for cystoscopy.

Xpert is an easy-to-perform urine test with good performance compared with standard urine tests. It should help optimize the follow-up of recurrent bladder cancer patients.

European urology. 2018 Dec 12 [Epub ahead of print]

F Johannes P van Valenberg, Andrew M Hiar, Ellen Wallace, Julia A Bridge, Donna J Mayne, Safedin Beqaj, Wade J Sexton, Yair Lotan, Alon Z Weizer, Godfrey K Jansz, Arnulf Stenzl, John F Danella, Barry Shepard, Kevin J Cline, Michael B Williams, Scott Montgomery, Richard D David, Richard Harris, Eric W Klein, Timothy J Bradford, Fred N Wolk, Karl R Westenfelder, Andrew F Trainer, Timothy A Richardson, Russell B Egerdie, Bernard Goldfarb, Joseph A Zadra, Sijian Ge, Suling Zhao, Iris M Simon, Scott A Campbell, Brian Rhees, Michael P Bates, Russell G Higuchi, J Alfred Witjes

Radboudumc, Nijmegen, The Netherlands. Electronic address: ., Cepheid, Sunnyvale, CA, USA., UNMC, Omaha, NE, USA., Sacred Heart Hospital, Pensacola, FL, USA., Pathology, Inc., Torrance, CA, USA., Moffitt Cancer Center, Tampa, FL, USA., UT Southwestern Medical Center, Dallas, TX, USA., University of Michigan Hospital, Ann Arbor, MI, USA., Urology Office of G. Kenneth Jansz, Burlington, Ontario, Canada., University Medical Clinic of Tuebingen, Tuebingen, Germany., Geisinger Health System, Danville, PA, USA., Urological Surgeons of Long Island, PLLC, Garden City, NY, USA., Regional Urology, Shreveport, LA, USA., Urology of Virginia, Virginia Beach, VA, USA., Kansas City Urology Care, Overland Park, KS, USA., Skyline Urology, Torrance, CA, USA., UroPartners, Melrose Park, IL, USA., Idaho Urologic Institute, Meridian, ID, USA., Virginia Urology, Richmond, VA, USA., Skyline Urology, Sherman Oaks, CA, USA., Five Valleys Urology, Missoula, MT, USA., Adult and Pediatric Urology, Omaha, NE, USA., Wichita Urology Group, Wichita, KS, USA., Urology Office of R. Blaire Egerdie, Kitchener, Ontario, Canada., North Bay, Ontario, Canada., Barrie, Ontario, Canada., Radboudumc, Nijmegen, The Netherlands.