Development of a 90-Minute Integrated Noninvasive Urinary Assay for Bladder Cancer Detection

Ellen Wallace, Russell Higuchi, Malini Satya, Leena McCann, Mandy L.Y. 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 & 3 others Yair Lotan, Bernard Goldfarb, Joseph C. Liao

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Purpose: Despite suboptimal sensitivity urine cytology is often performed as an adjunct to cystoscopy for bladder cancer diagnosis. We aimed to develop a noninvasive, fast molecular diagnostic test for bladder cancer detection with better sensitivity than urine cytology while maintaining adequate specificity. Materials and Methods: 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 10 urinary mRNAs were measured in a training cohort of 483 subjects and regression analysis was used to identify a 5-mRNA model to predict cancer status. The performance of the GeneXpert® Bladder Cancer Assay, an assay labeled for investigational use only to detect the 5 mRNAs ABL1, CRH, IGF2, ANXA10 and UPK1B, was evaluated in an independent test cohort of 450 participants. Results: In the independent test cohort the assay ROC curve AUC was 0.87 (95% CI 0.81-0.92). At an example cutoff point of 0.4 overall sensitivity was 73% while specificity was 90% and 77% in the hematuria and surveillance patient populations, respectively. Conclusions: We developed a 90-minute, urine based test that is simple to perform for the detection of bladder cancer. The test can help guide physician decision making in the management of bladder cancer. Additional evaluation in a prospective study is needed to establish the clinical usefulness of this assay.

Original languageEnglish (US)
JournalJournal of Urology
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Urinary Bladder Neoplasms
Urine
Cystoscopy
Messenger RNA
Cell Biology
Population Surveillance
Molecular Pathology
Hematuria
Routine Diagnostic Tests
ROC Curve
Area Under Curve
Neoplasms
Decision Making
Regression Analysis
Prospective Studies
Physicians

Keywords

  • Early detection of cancer
  • Hematuria
  • Messenger
  • Molecular
  • Pathology
  • RNA
  • Urinary bladder neoplasms

ASJC Scopus subject areas

  • Urology

Cite this

Wallace, E., Higuchi, R., Satya, M., McCann, L., Sin, M. L. Y., Bridge, J. A., ... Liao, J. C. (Accepted/In press). Development of a 90-Minute Integrated Noninvasive Urinary Assay for Bladder Cancer Detection. Journal of Urology. https://doi.org/10.1016/j.juro.2017.09.141

Development of a 90-Minute Integrated Noninvasive Urinary Assay for Bladder Cancer Detection. / Wallace, Ellen; Higuchi, Russell; Satya, Malini; McCann, Leena; Sin, Mandy L.Y.; Bridge, Julia A.; Wei, Huilin; Zhang, Jun; Wong, Edith; Hiar, Andrew; Mach, Kathleen E.; Scherr, Douglas; Egerdie, R. Blair; Ohta, Shoichiro; Sexton, Wade J.; Meng, Maxwell V.; Weizer, Alon Z.; Woods, Michael; Jansz, G. Kenneth; Zadra, Joseph; Lotan, Yair; Goldfarb, Bernard; Liao, Joseph C.

In: Journal of Urology, 01.01.2018.

Research output: Contribution to journalArticle

Wallace, E, Higuchi, R, Satya, M, McCann, L, Sin, MLY, Bridge, JA, Wei, H, Zhang, J, Wong, E, Hiar, A, Mach, KE, Scherr, D, Egerdie, RB, Ohta, S, Sexton, WJ, Meng, MV, Weizer, AZ, Woods, M, Jansz, GK, Zadra, J, Lotan, Y, Goldfarb, B & Liao, JC 2018, 'Development of a 90-Minute Integrated Noninvasive Urinary Assay for Bladder Cancer Detection', Journal of Urology. https://doi.org/10.1016/j.juro.2017.09.141
Wallace, Ellen ; Higuchi, Russell ; Satya, Malini ; McCann, Leena ; Sin, Mandy L.Y. ; Bridge, Julia A. ; Wei, Huilin ; Zhang, Jun ; Wong, Edith ; Hiar, Andrew ; Mach, Kathleen E. ; Scherr, Douglas ; Egerdie, R. Blair ; Ohta, Shoichiro ; Sexton, Wade J. ; Meng, Maxwell V. ; Weizer, Alon Z. ; Woods, Michael ; Jansz, G. Kenneth ; Zadra, Joseph ; Lotan, Yair ; Goldfarb, Bernard ; Liao, Joseph C. / Development of a 90-Minute Integrated Noninvasive Urinary Assay for Bladder Cancer Detection. In: Journal of Urology. 2018.
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abstract = "Purpose: Despite suboptimal sensitivity urine cytology is often performed as an adjunct to cystoscopy for bladder cancer diagnosis. We aimed to develop a noninvasive, fast molecular diagnostic test for bladder cancer detection with better sensitivity than urine cytology while maintaining adequate specificity. Materials and Methods: 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 10 urinary mRNAs were measured in a training cohort of 483 subjects and regression analysis was used to identify a 5-mRNA model to predict cancer status. The performance of the GeneXpert{\circledR} Bladder Cancer Assay, an assay labeled for investigational use only to detect the 5 mRNAs ABL1, CRH, IGF2, ANXA10 and UPK1B, was evaluated in an independent test cohort of 450 participants. Results: In the independent test cohort the assay ROC curve AUC was 0.87 (95{\%} CI 0.81-0.92). At an example cutoff point of 0.4 overall sensitivity was 73{\%} while specificity was 90{\%} and 77{\%} in the hematuria and surveillance patient populations, respectively. Conclusions: We developed a 90-minute, urine based test that is simple to perform for the detection of bladder cancer. The test can help guide physician decision making in the management of bladder cancer. Additional evaluation in a prospective study is needed to establish the clinical usefulness of this assay.",
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AU - Wallace, Ellen

AU - Higuchi, Russell

AU - Satya, Malini

AU - McCann, Leena

AU - Sin, Mandy L.Y.

AU - Bridge, Julia A.

AU - Wei, Huilin

AU - Zhang, Jun

AU - Wong, Edith

AU - Hiar, Andrew

AU - Mach, Kathleen E.

AU - Scherr, Douglas

AU - Egerdie, R. Blair

AU - Ohta, Shoichiro

AU - Sexton, Wade J.

AU - Meng, Maxwell V.

AU - Weizer, Alon Z.

AU - Woods, Michael

AU - Jansz, G. Kenneth

AU - Zadra, Joseph

AU - Lotan, Yair

AU - Goldfarb, Bernard

AU - Liao, Joseph C.

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N2 - Purpose: Despite suboptimal sensitivity urine cytology is often performed as an adjunct to cystoscopy for bladder cancer diagnosis. We aimed to develop a noninvasive, fast molecular diagnostic test for bladder cancer detection with better sensitivity than urine cytology while maintaining adequate specificity. Materials and Methods: 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 10 urinary mRNAs were measured in a training cohort of 483 subjects and regression analysis was used to identify a 5-mRNA model to predict cancer status. The performance of the GeneXpert® Bladder Cancer Assay, an assay labeled for investigational use only to detect the 5 mRNAs ABL1, CRH, IGF2, ANXA10 and UPK1B, was evaluated in an independent test cohort of 450 participants. Results: In the independent test cohort the assay ROC curve AUC was 0.87 (95% CI 0.81-0.92). At an example cutoff point of 0.4 overall sensitivity was 73% while specificity was 90% and 77% in the hematuria and surveillance patient populations, respectively. Conclusions: We developed a 90-minute, urine based test that is simple to perform for the detection of bladder cancer. The test can help guide physician decision making in the management of bladder cancer. Additional evaluation in a prospective study is needed to establish the clinical usefulness of this assay.

AB - Purpose: Despite suboptimal sensitivity urine cytology is often performed as an adjunct to cystoscopy for bladder cancer diagnosis. We aimed to develop a noninvasive, fast molecular diagnostic test for bladder cancer detection with better sensitivity than urine cytology while maintaining adequate specificity. Materials and Methods: 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 10 urinary mRNAs were measured in a training cohort of 483 subjects and regression analysis was used to identify a 5-mRNA model to predict cancer status. The performance of the GeneXpert® Bladder Cancer Assay, an assay labeled for investigational use only to detect the 5 mRNAs ABL1, CRH, IGF2, ANXA10 and UPK1B, was evaluated in an independent test cohort of 450 participants. Results: In the independent test cohort the assay ROC curve AUC was 0.87 (95% CI 0.81-0.92). At an example cutoff point of 0.4 overall sensitivity was 73% while specificity was 90% and 77% in the hematuria and surveillance patient populations, respectively. Conclusions: We developed a 90-minute, urine based test that is simple to perform for the detection of bladder cancer. The test can help guide physician decision making in the management of bladder cancer. Additional evaluation in a prospective study is needed to establish the clinical usefulness of this assay.

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KW - Pathology

KW - RNA

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