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Validation of a mRNA-based urine test for bladder cancer detection in patients with hematuria
32nd Annual EAU Congress, 24-28 March 2017, London, United Kingdom
117
Validation of a mRNA-based urine test for bladder cancer detection in patients with hematuria Eur Urol Suppl 2017; 16(3);e190
Van Valenberg F.J.P.1, Bridge J.A.2, Mayne D.3, Beqaj S.4, Sexton W.J.5, Lotan Y.6, Weizer A.Z.7, Jansz G.K.8, Stenzl A.9, Danella J.F.10, Shepard B.R.11, Cline K.J.12, Williams M.B.13, Montgomery T.14, David R.D.15, Harris R.G.16, Klein E.W.17, Bradford T.J.18, Wolk F.N.19, Westenfelder K.R.20, Trainer A.F.21, Richardson T.A.22, Witjes J.A.1 1
Radboudumc, Dept. of Urology, Nijmegen, The Netherlands, 2University of Nebraska Medical Center, Departments of Pathology/Microbiology, Pediatrics and Orthopaedic Surgery, Omaha, United States of America, 3Sacred Heart Hospital, Molecular Laboratory, Pensacola, United States of America, 4 Pathology Inc., Clinical Laboratory, Torrance, United States of America, 5Moffitt Cancer Center, Genitourinary Oncology and Oncologic Sciences, Tampa, United States of America, 6University of Texas Southwestern, Dept. of Urology, Dallas, United States of America, 7University of Michigan Hospital, Dept. of Urology, Ann Arbor, United States of America, 8G. Kenneth Jansz MPC, Private Practice, Burlington, Canada, 9University of Tübingen, Dept. of Urology, Tübingen, Germany, 10Geisinger Health System, Dept. of Urology, Danville, United States of America, 11Urological Surgeons of Long Island, PLLC, Private Practice, Garden City, United States of America, 12Regional Urology, Private Practice, Shreveport, United States of America, 13Urology of Virginia, Private Practice, Virginia Beach, United States of America, 14Kansas City Urology Care, Private Practice, Overland Park, United States of America, 15Skyline Urology, Private Practice, Torrance, United States of America, 16UroPartners, Private Practice, Melrose Park, United States of America, 17Idaho Urologic Institute, Private Practice, Meridian, United States of America, 18Virginia Urology, Private Practice, Richmond, United States of America, 19 Skyline Urology, Private Practice, Sherman Oaks, United States of America, 20Five Valleys Urology, Private Practice, Missoula, United States of America, 21Adult and Pediatric Urology & Urogynecology, Private Practice, Omaha, United States of America, 22Wichita Urology Group, Private Practice, Wichita, United States of America INTRODUCTION & OBJECTIVES: Diagnosis of bladder cancer (BC) currently requires invasive tests. There is an unmet need for a fast, non-invasive test with good sensitivity (SN), specificity (SP) and negative predictive value (NPV) for detection of primary BC. Xpert Bladder Cancer Detection (Xpert BC Detection) includes reagents for detection of 5 mRNA targets (CRH, IGF2, UPK1B, ANXA10, and ABL1) in urine that may be overexpressed in BC. The Xpert BC Detection automates and integrates sample processing, nucleic acid amplification and detection of the target sequences. Our aim was to evaluate the test performance of Xpert BC Detection in patients with hematuria. MATERIAL & METHODS: We performed a prospective, multicenter (22 sites) study in patients without prior history of BC who were undergoing cystoscopic examination for work up of microscopic or gross hematuria (symptomatic). Urine samples were collected prior to cystoscopy and treated within one hour of collection with the Xpert® Urine Transport Reagent Kit. Treated urine (4mL) was transferred to the sample chamber of the test cartridge. The cartridge was then placed into the GeneXpert System for
Eur Urol Suppl 2017; 16(3);e190
32nd Annual EAU Congress, 24-28 March 2017, London, United Kingdom
117
Validation of a mRNA-based urine test for bladder cancer detection in patients with hematuria Eur Urol Suppl 2017; 16(3);e191
sample processing, RT-PCR and detection. If cystoscopy was abnormal, tissue for histology was obtained. The assay hands-on time was less than 2 minutes and the time to result was approximately 90 minutes. Xpert BC Detection performance was compared with cytology, UroVysion®(Abbott Molecular, Des Plains, USA) and histology-confirmed cystoscopy results. RESULTS: The study included 895 subjects with a mean age of 62.3±13.6 (SD) years. Of these, 511 (57.1%) were male, and 434 (48.5%) never smoked. Table 1 presents the test characteristics for Xpert BC Detection, cytology and UroVysion® as compared to histology-confirmed cystoscopy. Xpert BC Detection had an overall SN of 75.8%, a SP of 84.6%, and a NPV of 97.8%. These test characteristics were superior to cytology and UroVysion®, except for the SP where cytology was best with a value of 97.3%. For High Grade (HG) disease, Xpert BC Detection had the highest SN (88.4%). Table 1: Overview of test characteristics (overall and HG) [95%-CI] Detection SN SP NPV HG SN
Xpert® 75.8 [64.2-84.5] 84.6 [81.9-86.9] 97.8 [96.4-98.6] 88.4 [75.5-94.9]
Cytology 40.3 [29.4-52.3] 97.3 [95.9-98.2] 95.1 [93.5-96.4] 59.5 [44.5-72.9]
UroVysion® 57.8 [45.6-69.1] 87.9 [85.4-90.0] 96.3 [94.7-97.4] 77.5 [62.5-87.7]
CONCLUSIONS: Xpert BC Detection has improved SN and NPV for detection of BC compared to cytology and UroVysion® in patients with hematuria. It represents a promising new tool for adjunctive use in combination with other diagnostic modalities to further optimize the detection of BC in hematuric patients.
Eur Urol Suppl 2017; 16(3);e191 Powered by TCPDF (www.tcpdf.org)
117
Validation of a mRNA-based urine test for bladder cancer detection in patients with hematuria Eur Urol Suppl 2017; 16(3);e190
Van Valenberg F.J.P.1, Bridge J.A.2, Mayne D.3, Beqaj S.4, Sexton W.J.5, Lotan Y.6, Weizer A.Z.7, Jansz G.K.8, Stenzl A.9, Danella J.F.10, Shepard B.R.11, Cline K.J.12, Williams M.B.13, Montgomery T.14, David R.D.15, Harris R.G.16, Klein E.W.17, Bradford T.J.18, Wolk F.N.19, Westenfelder K.R.20, Trainer A.F.21, Richardson T.A.22, Witjes J.A.1 1
Radboudumc, Dept. of Urology, Nijmegen, The Netherlands, 2University of Nebraska Medical Center, Departments of Pathology/Microbiology, Pediatrics and Orthopaedic Surgery, Omaha, United States of America, 3Sacred Heart Hospital, Molecular Laboratory, Pensacola, United States of America, 4 Pathology Inc., Clinical Laboratory, Torrance, United States of America, 5Moffitt Cancer Center, Genitourinary Oncology and Oncologic Sciences, Tampa, United States of America, 6University of Texas Southwestern, Dept. of Urology, Dallas, United States of America, 7University of Michigan Hospital, Dept. of Urology, Ann Arbor, United States of America, 8G. Kenneth Jansz MPC, Private Practice, Burlington, Canada, 9University of Tübingen, Dept. of Urology, Tübingen, Germany, 10Geisinger Health System, Dept. of Urology, Danville, United States of America, 11Urological Surgeons of Long Island, PLLC, Private Practice, Garden City, United States of America, 12Regional Urology, Private Practice, Shreveport, United States of America, 13Urology of Virginia, Private Practice, Virginia Beach, United States of America, 14Kansas City Urology Care, Private Practice, Overland Park, United States of America, 15Skyline Urology, Private Practice, Torrance, United States of America, 16UroPartners, Private Practice, Melrose Park, United States of America, 17Idaho Urologic Institute, Private Practice, Meridian, United States of America, 18Virginia Urology, Private Practice, Richmond, United States of America, 19 Skyline Urology, Private Practice, Sherman Oaks, United States of America, 20Five Valleys Urology, Private Practice, Missoula, United States of America, 21Adult and Pediatric Urology & Urogynecology, Private Practice, Omaha, United States of America, 22Wichita Urology Group, Private Practice, Wichita, United States of America INTRODUCTION & OBJECTIVES: Diagnosis of bladder cancer (BC) currently requires invasive tests. There is an unmet need for a fast, non-invasive test with good sensitivity (SN), specificity (SP) and negative predictive value (NPV) for detection of primary BC. Xpert Bladder Cancer Detection (Xpert BC Detection) includes reagents for detection of 5 mRNA targets (CRH, IGF2, UPK1B, ANXA10, and ABL1) in urine that may be overexpressed in BC. The Xpert BC Detection automates and integrates sample processing, nucleic acid amplification and detection of the target sequences. Our aim was to evaluate the test performance of Xpert BC Detection in patients with hematuria. MATERIAL & METHODS: We performed a prospective, multicenter (22 sites) study in patients without prior history of BC who were undergoing cystoscopic examination for work up of microscopic or gross hematuria (symptomatic). Urine samples were collected prior to cystoscopy and treated within one hour of collection with the Xpert® Urine Transport Reagent Kit. Treated urine (4mL) was transferred to the sample chamber of the test cartridge. The cartridge was then placed into the GeneXpert System for
Eur Urol Suppl 2017; 16(3);e190
32nd Annual EAU Congress, 24-28 March 2017, London, United Kingdom
117
Validation of a mRNA-based urine test for bladder cancer detection in patients with hematuria Eur Urol Suppl 2017; 16(3);e191
sample processing, RT-PCR and detection. If cystoscopy was abnormal, tissue for histology was obtained. The assay hands-on time was less than 2 minutes and the time to result was approximately 90 minutes. Xpert BC Detection performance was compared with cytology, UroVysion®(Abbott Molecular, Des Plains, USA) and histology-confirmed cystoscopy results. RESULTS: The study included 895 subjects with a mean age of 62.3±13.6 (SD) years. Of these, 511 (57.1%) were male, and 434 (48.5%) never smoked. Table 1 presents the test characteristics for Xpert BC Detection, cytology and UroVysion® as compared to histology-confirmed cystoscopy. Xpert BC Detection had an overall SN of 75.8%, a SP of 84.6%, and a NPV of 97.8%. These test characteristics were superior to cytology and UroVysion®, except for the SP where cytology was best with a value of 97.3%. For High Grade (HG) disease, Xpert BC Detection had the highest SN (88.4%). Table 1: Overview of test characteristics (overall and HG) [95%-CI] Detection SN SP NPV HG SN
Xpert® 75.8 [64.2-84.5] 84.6 [81.9-86.9] 97.8 [96.4-98.6] 88.4 [75.5-94.9]
Cytology 40.3 [29.4-52.3] 97.3 [95.9-98.2] 95.1 [93.5-96.4] 59.5 [44.5-72.9]
UroVysion® 57.8 [45.6-69.1] 87.9 [85.4-90.0] 96.3 [94.7-97.4] 77.5 [62.5-87.7]
CONCLUSIONS: Xpert BC Detection has improved SN and NPV for detection of BC compared to cytology and UroVysion® in patients with hematuria. It represents a promising new tool for adjunctive use in combination with other diagnostic modalities to further optimize the detection of BC in hematuric patients.
Eur Urol Suppl 2017; 16(3);e191 Powered by TCPDF (www.tcpdf.org)