Validation of an mRNA-based Urine Test for the Detection of Bladder Cancer in Patients with Haematuria.

Bladder cancer Cystoscopy Diagnostic test Non–muscle-invasive bladder cancer Sensitivity Specificity Urine test mRNA

Journal

European urology oncology
ISSN: 2588-9311
Titre abrégé: Eur Urol Oncol
Pays: Netherlands
ID NLM: 101724904

Informations de publication

Date de publication:
02 2021
Historique:
received: 27 04 2020
revised: 04 08 2020
accepted: 01 09 2020
pubmed: 3 10 2020
medline: 20 11 2021
entrez: 2 10 2020
Statut: ppublish

Résumé

In patients with haematuria, a fast, noninvasive test with high sensitivity (SN) and negative predictive value (NPV), which is able to detect or exclude bladder cancer (BC), is needed. A newly developed urine assay, Xpert Bladder Cancer Detection (Xpert), measures five mRNA targets (ABL1, CRH, IGF2, UPK1B, and ANXA10) that are frequently overexpressed in BC. To validate the performance of Xpert in patients with haematuria. Voided precystoscopy urine specimens were prospectively collected at 22 sites from patients without prior BC undergoing cystoscopy for haematuria. Xpert, cytology, and UroVysion procedures were performed. Technical validation was performed and specificity (SP) was determined in patients without BC. Test characteristics were calculated based on cystoscopy and histology results, and compared between Xpert, cytology, and UroVysion. We included 828 patients (mean age 64.5 yr, 467 males, 401 never smoked). Xpert had an SN of 78% (95% confidence interval [CI]: 66-87) overall and 90% (95% CI: 76-96) for high-grade (HG) tumours. The NPV was 98% (95% CI: 97-99) overall. The SP was 84% (95% CI: 81-86). In patients with microhaematuria, only one HG patient was missed (NPV 99%). Xpert had higher SN and NPV than cytology and UroVysion. Cytology had the highest SP (97%). In a separate SP study, Xpert had an SP of 89% in patients with benign prostate hypertrophy and 92% in prostate cancer patients. Xpert is an easy-to-use, noninvasive test with improved SN and NPV compared with cytology and UroVysion, representing a promising tool for identifying haematuric patients with a low likelihood of BC who might not need to undergo cystoscopy. Xpert is an easy-to-perform urine test with good performance compared with standard urine tests. It should help identify (micro)haematuria patients with a very low likelihood to have bladder cancer.

Sections du résumé

BACKGROUND
In patients with haematuria, a fast, noninvasive test with high sensitivity (SN) and negative predictive value (NPV), which is able to detect or exclude bladder cancer (BC), is needed. A newly developed urine assay, Xpert Bladder Cancer Detection (Xpert), measures five mRNA targets (ABL1, CRH, IGF2, UPK1B, and ANXA10) that are frequently overexpressed in BC.
OBJECTIVE
To validate the performance of Xpert in patients with haematuria.
DESIGN, SETTING, AND PARTICIPANTS
Voided precystoscopy urine specimens were prospectively collected at 22 sites from patients without prior BC undergoing cystoscopy for haematuria. Xpert, cytology, and UroVysion procedures were performed. Technical validation was performed and specificity (SP) was determined in patients without BC.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS
Test characteristics were calculated based on cystoscopy and histology results, and compared between Xpert, cytology, and UroVysion.
RESULTS AND LIMITATIONS
We included 828 patients (mean age 64.5 yr, 467 males, 401 never smoked). Xpert had an SN of 78% (95% confidence interval [CI]: 66-87) overall and 90% (95% CI: 76-96) for high-grade (HG) tumours. The NPV was 98% (95% CI: 97-99) overall. The SP was 84% (95% CI: 81-86). In patients with microhaematuria, only one HG patient was missed (NPV 99%). Xpert had higher SN and NPV than cytology and UroVysion. Cytology had the highest SP (97%). In a separate SP study, Xpert had an SP of 89% in patients with benign prostate hypertrophy and 92% in prostate cancer patients.
CONCLUSIONS
Xpert is an easy-to-use, noninvasive test with improved SN and NPV compared with cytology and UroVysion, representing a promising tool for identifying haematuric patients with a low likelihood of BC who might not need to undergo cystoscopy.
PATIENT SUMMARY
Xpert is an easy-to-perform urine test with good performance compared with standard urine tests. It should help identify (micro)haematuria patients with a very low likelihood to have bladder cancer.

Identifiants

pubmed: 33004290
pii: S2588-9311(20)30141-3
doi: 10.1016/j.euo.2020.09.001
pii:
doi:

Substances chimiques

RNA, Messenger 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

93-101

Informations de copyright

Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.

Auteurs

Franciscus Johannes P van Valenberg (FJPV)

Department of Urology, Radboudumc, Nijmegen, The Netherlands. Electronic address: hans.vanvalenberg@radboudumc.nl.

Andrew M Hiar (AM)

Cepheid, Sunnyvale, CA, USA.

Ellen Wallace (E)

Cepheid, Sunnyvale, CA, USA.

Julia A Bridge (JA)

University of Nebraska Medical Center, Omaha, NE, USA.

Donna J Mayne (DJ)

Sacred Heart Hospital, Pensacola, FL, USA.

Safedin Beqaj (S)

Pathology, Inc, Torrance, CA, USA.

Wade J Sexton (WJ)

Department of Genitourinary Oncology, Moffitt Cancer Center, Tampa, FL, USA.

Yair Lotan (Y)

UT Southwestern Medical Center, Dallas, TX, USA.

Alon Z Weizer (AZ)

University of Michigan Hospital, Ann Arbor, MI, USA.

Godfrey K Jansz (GK)

Urology Office of G. Kenneth Janz, Burlington, Ontario, Canada.

Arnulf Stenzl (A)

Department of Urology, University Medical Clinic of Tübingen, Tübingen, Germany.

John F Danella (JF)

Geisinger Health System, Danville, PA, USA.

Kevin J Cline (KJ)

Regional Urology, Shreveport, LA, USA.

Michael B Williams (MB)

Urology of Virginia, Virginia Beach, VA, USA.

Scott Montgomery (S)

Kansas City Urology Care, Overland Park, KS, USA.

Richard D David (RD)

Skyline Urology, Torrance, CA, USA.

Richard Harris (R)

UroPartners, Melrose Park, IL, USA.

Eric W Klein (EW)

Idaho Urologic Institute, Meridian, ID, USA.

Timothy J Bradford (TJ)

Virginia Urology, Richmond, VA, USA.

Fred N Wolk (FN)

Skyline Urology, Sherman Oaks, CA, USA.

Karl R Westenfelder (KR)

Five Valleys Urology, Missoula, MT, USA.

Andrew F Trainer (AF)

Adult, Pediatric Urology, Omaha, NE, USA.

Timothy A Richardson (TA)

Wichita Urology Group, Wichita, KS, USA.

Russell B Egerdie (RB)

Urology Associates/Urologic Medical Research, Kitchener, Ontario, Canada.

Bernard Goldfarb (B)

North Bay, Ontario, Canada.

Joseph A Zadra (JA)

Barrie, Ontario, Canada.

Xixi Lu (X)

Cepheid, Sunnyvale, CA, USA.

Iris M Simon (IM)

Cepheid, Sunnyvale, CA, USA.

Scott A Campbell (SA)

Cepheid, Sunnyvale, CA, USA.

Michael P Bates (MP)

Cepheid, Sunnyvale, CA, USA.

Russell G Higuchi (RG)

Cepheid, Sunnyvale, CA, USA.

J Alfred Witjes (JA)

Department of Urology, Radboudumc, Nijmegen, The Netherlands.

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