DETECT I: Detecting Bladder Cancer Using the UroMark Test.
Study Details
Study Description
Brief Summary
DETECT I is a prospective multicentre observational diagnostic study to assess the performance of the UroMark assay to rule out bladder cancer in patients with haematuria. The study will recruit consecutive patients attending haematuria clinics as well as patients referred to urology outpatient clinics for investigation of haematuria. Consenting patients will be provided with a urine sample collection kit and asked to provide a urine sample. An additional urine sample for control assay testing will be provided after the clinic attendance.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
Transitional cell carcinoma (TCC) of the urinary bladder is responsible for >12,000 new cases of cancer and >5,000 deaths per year in England and Wales. Most bladder cancers are non-muscle invasive bladder cancer (NMIBC) and do not invade deeply at presentation, but 80% of tumours recur within 3 years. For muscle invasive bladder cancer (MIBC), the 5 year survival is around 50%. Cystoscopy is the standard test for detection of bladder cancer along with imaging to assess the upper tracts and the common presenting symptom is haematuria. Cystoscopy is an invasive procedure and results in urinary infection in up to 5% of cases. Cystoscopy is performed under local anaesthetic and patients are required to attend hospital clinics for the test. About one in 10 patients who are investigated for haematuria will be found to have bladder cancer. Frequently, patients are not referred for investigation of haematuria at the time of first presentation and there is a delay in diagnosis of the disease. The early detection of bladder cancer by means of a non-invasive tumour marker test would impact on the management of the disease. There is an unmet need for a simple, non-invasive, highly sensitive and specific method for detecting bladder cancer.
This study will determine the accuracy of UroMark a high-throughput multiplex PCR test to detect bladder cancer in DNA from urine. The study will address the unmet clinical need to improve detection of bladder cancer. The rationale for the trial is based on proof of concept studies which provide compelling evidence that a panel of methylation markers can be applied to detect bladder cancer with high sensitivity and specificity. It will be also be possible to collect and store fractions of urine for assessment of other DNA related biomarkers as well as non-DNA assays for example cellular proteins, soluble biomarkers in urine supernatant and RNA transcripts in sediment cells. In this study we will compare the UroMark assay with established assays including urinary cytology, FISH as well as developing assays such as MCM5. In this proposal excess urine will be stored for these studies.
Study Design
Outcome Measures
Primary Outcome Measures
- Negative predictive value (NPV) of the UroMark test. [Baseline]
Secondary Outcome Measures
- Negative predictive value (NPV) of control assay (FDA approved urinary marker (UroVision)). [Baseline]
- Negative predictive value (NPV) against imaging (ultrasound/CT) [Baseline]
- Negative predictive value (NPV) against combination of UroMark and imaging. [Baseline]
Eligibility Criteria
Criteria
Inclusion Criteria:
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Participants must be over 18 years of age.
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Participants undergoing investigation for visible and non-visible haematuria.
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Able to give informed written consent.
Exclusion Criteria:
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Unwilling to have standard haematuria investigations.
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Unable to give informed consent.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UCLH | London | United Kingdom | NW1 2BU | |
| 2 | James Cook University Hospital | Middlesbrough | United Kingdom |
Sponsors and Collaborators
- University College, London
Investigators
- Principal Investigator: John Kelly, FRCS (urol), UCL
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Chan AW, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Krleža-Jerić K, Hróbjartsson A, Mann H, Dickersin K, Berlin JA, Doré CJ, Parulekar WR, Summerskill WS, Groves T, Schulz KF, Sox HC, Rockhold FW, Rennie D, Moher D. SPIRIT 2013 statement: defining standard protocol items for clinical trials. Ann Intern Med. 2013 Feb 5;158(3):200-7. doi: 10.7326/0003-4819-158-3-201302050-00583.
- Chan AW, Tetzlaff JM, Gøtzsche PC, Altman DG, Mann H, Berlin JA, Dickersin K, Hróbjartsson A, Schulz KF, Parulekar WR, Krleza-Jeric K, Laupacis A, Moher D. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials. BMJ. 2013 Jan 8;346:e7586. doi: 10.1136/bmj.e7586.
- Coenen MJ, Ploeg M, Schijvenaars MM, Cornel EB, Karthaus HF, Scheffer H, Witjes JA, Franke B, Kiemeney LA. Allelic imbalance analysis using a single-nucleotide polymorphism microarray for the detection of bladder cancer recurrence. Clin Cancer Res. 2008 Dec 15;14(24):8198-204. doi: 10.1158/1078-0432.CCR-08-1103.
- Dudderidge TJ, Kelly JD, Wollenschlaeger A, Okoturo O, Prevost T, Robson W, Leung HY, Williams GH, Stoeber K. Diagnosis of prostate cancer by detection of minichromosome maintenance 5 protein in urine sediments. Br J Cancer. 2010 Aug 24;103(5):701-7. doi: 10.1038/sj.bjc.6605785. Epub 2010 Jul 20.
- Edwards TJ, Dickinson AJ, Natale S, Gosling J, McGrath JS. A prospective analysis of the diagnostic yield resulting from the attendance of 4020 patients at a protocol-driven haematuria clinic. BJU Int. 2006 Feb;97(2):301-5; discussion 305.
- Hoque MO, Begum S, Topaloglu O, Chatterjee A, Rosenbaum E, Van Criekinge W, Westra WH, Schoenberg M, Zahurak M, Goodman SN, Sidransky D. Quantitation of promoter methylation of multiple genes in urine DNA and bladder cancer detection. J Natl Cancer Inst. 2006 Jul 19;98(14):996-1004.
- Kelly JD, Fawcett DP, Goldberg LC. Assessment and management of non-visible haematuria in primary care. BMJ. 2009 Jan 16;338:a3021. doi: 10.1136/bmj.a3021. Review.
- Khadra MH, Pickard RS, Charlton M, Powell PH, Neal DE. A prospective analysis of 1,930 patients with hematuria to evaluate current diagnostic practice. J Urol. 2000 Feb;163(2):524-7.
- Lotan Y, Elias K, Svatek RS, Bagrodia A, Nuss G, Moran B, Sagalowsky AI. Bladder cancer screening in a high risk asymptomatic population using a point of care urine based protein tumor marker. J Urol. 2009 Jul;182(1):52-7; discussion 58. doi: 10.1016/j.juro.2009.02.142. Epub 2009 May 17.
- Lyratzopoulos G, Abel GA, McPhail S, Neal RD, Rubin GP. Gender inequalities in the promptness of diagnosis of bladder and renal cancer after symptomatic presentation: evidence from secondary analysis of an English primary care audit survey. BMJ Open. 2013 Jun 24;3(6). pii: e002861. doi: 10.1136/bmjopen-2013-002861.
- Malmström PU, Sylvester RJ, Crawford DE, Friedrich M, Krege S, Rintala E, Solsona E, Di Stasi SM, Witjes JA. An individual patient data meta-analysis of the long-term outcome of randomised studies comparing intravesical mitomycin C versus bacillus Calmette-Guérin for non-muscle-invasive bladder cancer. Eur Urol. 2009 Aug;56(2):247-56. doi: 10.1016/j.eururo.2009.04.038. Epub 2009 Apr 24.
- Mitra AP, Cote RJ. Molecular screening for bladder cancer: progress and potential. Nat Rev Urol. 2010 Jan;7(1):11-20. doi: 10.1038/nrurol.2009.236. Review.
- Mowatt G, N'Dow J, Vale L, Nabi G, Boachie C, Cook JA, Fraser C, Griffiths TR; Aberdeen Technology Assessment Review (TAR) Group. Photodynamic diagnosis of bladder cancer compared with white light cystoscopy: Systematic review and meta-analysis. Int J Technol Assess Health Care. 2011 Jan;27(1):3-10. doi: 10.1017/S0266462310001364. Epub 2011 Jan 25. Review.
- Rodgers M, Nixon J, Hempel S, Aho T, Kelly J, Neal D, Duffy S, Ritchie G, Kleijnen J, Westwood M. Diagnostic tests and algorithms used in the investigation of haematuria: systematic reviews and economic evaluation. Health Technol Assess. 2006 Jun;10(18):iii-iv, xi-259. Review.
- Sangar VK, Ragavan N, Matanhelia SS, Watson MW, Blades RA. The economic consequences of prostate and bladder cancer in the UK. BJU Int. 2005 Jan;95(1):59-63.
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