title: Performance Characteristics of a Multigene Urine Biomarker Test for Monitoring for Recurrent Urothelial Carcinoma in a Multicenter Study.
abstract: Urothelial carcinoma is associated with a high rate of recurrence. Guidelines recommend rigorous, regular surveillance programs that are invasive and expensive. This study describes a noninvasive urine test with sufficient sensitivity to rule out recurrent urothelial carcinoma, thereby reducing invasive diagnostic evaluations without compromising patient care.
  
  
  
  A total of 1,036 urine samples were prospectively collected from 763 patients undergoing routine surveillance for recurrent urothelial carcinoma of the bladder. The purpose was to develop and validate a test with combined high sensitivity and high negative predictive value. Cxbladder Monitor combines gene expression, clinical and patient data, and it is designed to rule out the presence of recurrent urothelial carcinoma.
  
  
  
  Cxbladder Monitor showed an internally validated sensitivity of 0.93 with a negative predictive value of 0.97 and a test negative rate of 0.34. Sensitivity was 0.95 for recurrent disease with a high risk of progression (all high grade disease and low grade, stage T1 or greater disease) compared with 0.86 for low grade Ta disease. Subgroup analyses indicated that diagnostic performance was not significantly different in different age groups, or by gender or tumor stage. Sensitivity was not affected by adjuvant bacillus Calmette-Guérin treatment within the last 6 months. False-negative findings were reported in fewer than 1.5% of all samples collected.
  
  
  
  The Cxbladder Monitor test offers combined high sensitivity and high negative predictive value to rule out urothelial carcinoma. This test has clinical utility as a confirmatory negative adjunct to cystoscopy, potentially justifying the postponement/avoidance of cystoscopic investigations to monitor recurrence in patients.
authors.affiliation: Pacific Edge Ltd., Dunedin, New Zealand.
authors.forename: Laimonis
authors.initials: L
authors.lastname: Kavalieris
authors.affiliation: Pacific Edge Ltd., Dunedin, New Zealand.
authors.forename: Paul
authors.initials: P
authors.lastname: O'Sullivan
authors.affiliation: Department of Medicine, University of Otago, Christchurch, New Zealand.
authors.forename: Chris
authors.initials: C
authors.lastname: Frampton
authors.affiliation: Pacific Edge Ltd., Dunedin, New Zealand; Department of Biochemistry, University of Otago, Dunedin, New Zealand.
authors.forename: Parry
authors.initials: P
authors.lastname: Guilford
authors.affiliation: Pacific Edge Ltd., Dunedin, New Zealand.
authors.forename: David
authors.initials: D
authors.lastname: Darling
authors.affiliation: Pacific Edge Ltd., Dunedin, New Zealand.
authors.forename: Elsie
authors.initials: E
authors.lastname: Jacobson
authors.affiliation: Pacific Edge Ltd., Dunedin, New Zealand. Electronic address: jimmy.suttie@pelnz.com.
authors.forename: James
authors.initials: J
authors.lastname: Suttie
authors.affiliation: Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Raman
authors.affiliation: Department of Urology, Weill Cornell Medical College, Cornell University, New York, New York; Department of Urology Medical University of Vienna, Vienna, Austria; Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D002295:Carcinoma, Transitional Cell / Q000235:genetics / Q000652:urine*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000652:urine*; D011159:Population Surveillance; D011237:Predictive Value of Tests; D011446:Prospective Studies; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000652:urine*
chemical_list: D014408:Biomarkers, Tumor
keywords: biomarkers; diagnostic techniques; local; molecular diagnostic techniques; neoplasm recurrence; tumor; urinary bladder neoplasms; urological