Wei Shen Tan1, Wei Phin Tan2, Mae-Yen Tan3, Pramit Khetrapal4, Liqin Dong5, Patricia deWinter6, Andrew Feber5, John D Kelly4. 1. Division of Surgery and Interventional Science, University College London, 3rd Floor Charles Bell House, 43-45 Foley Street, London W1W 7TS, UK; Department of Urology, University College London Hospital at Westmoreland Street, 16-18 Westmoreland Street, London W1G 8PH, UK. Electronic address: wei.tan@ucl.ac.uk. 2. Department of Urology, Rush University Medical Center, 1653 W Congress Pkwy, Chicago, IL 60612, USA. 3. School of Public Health, London School of Hygiene & Tropical Medicine, Keppel Street, London WC1E 7HT, UK. 4. Division of Surgery and Interventional Science, University College London, 3rd Floor Charles Bell House, 43-45 Foley Street, London W1W 7TS, UK; Department of Urology, University College London Hospital at Westmoreland Street, 16-18 Westmoreland Street, London W1G 8PH, UK. 5. UCL Cancer Institute, University College London, Paul O'Gorman Building, 72 Huntley Street, London WC1E 6DD, UK. 6. Division of Surgery and Interventional Science, University College London, 3rd Floor Charles Bell House, 43-45 Foley Street, London W1W 7TS, UK.
Abstract
BACKGROUND: Urinary biomarkers for the diagnosis of bladder cancer represents an area of considerable research which has been tested in both patients presenting with haematuria and non-muscle invasive bladder cancer patients requiring surveillance cystoscopy. In this systematic review, we identify and appraise the diagnostic sensitive and specificity of reported novel biomarkers of different 'omic' class and highlight promising biomarkers investigated to date. METHODS: A MEDLINE/Pubmed systematic search was performed between January 2013 and July 2017 using the following keywords: (bladder cancer OR transitional cell carcinoma OR urothelial cell carcinoma) AND (detection OR diagnosis) AND urine AND (biomarker OR assay). All studies had a minimum of 20 patients in both bladder cancer and control arms and reported sensitivity and/or specificity and/or receiver operating characteristics (ROC) curve. QUADAS-2 tool was used to assess risk of bias and applicability of studies. The search protocol was registered in the PROSPERO database (CRD42016049918). RESULTS: Systematic search yielded 115 reports were included for analysis. In single target biomarkers had a sensitivity of 2-94%, specificity of 46-100%, positive predictive value (PPV) of 47-100% and negative predictive value (NPV) of 21-94%. Multi-target biomarkers achieved a sensitivity of 24-100%, specificity of 48-100%, PPV of 42-95% and NPV of 32-100%. 50 studies achieved a sensitivity and specificity of ≥80%. Protein (n = 59) and transcriptomic (n = 21) biomarkers represents the most studied biomarkers. Multi-target biomarker panels had a better diagnostic accuracy compared to single biomarker targets. Urinary cytology with urinary biomarkers improved the diagnostic ability of the biomarker. The sensitivity and specificity of biomarkers were higher for primary diagnosis compared to patients in the surveillance setting. Most studies were case control studies and did not have a predefined threshold to determine a positive test result indicating a possible risk of bias. CONCLUSION: This comprehensive systematic review provides an update on urinary biomarkers of different 'omic' class and highlights promising biomarkers. Few biomarkers achieve a high sensitivity and negative predictive value. Such biomarkers will require external validation in a prospective observational setting before adoption in clinical practice.
BACKGROUND: Urinary biomarkers for the diagnosis of bladder cancer represents an area of considerable research which has been tested in both patients presenting with haematuria and non-muscle invasive bladder cancer patients requiring surveillance cystoscopy. In this systematic review, we identify and appraise the diagnostic sensitive and specificity of reported novel biomarkers of different 'omic' class and highlight promising biomarkers investigated to date. METHODS: A MEDLINE/Pubmed systematic search was performed between January 2013 and July 2017 using the following keywords: (bladder cancer OR transitional cell carcinoma OR urothelial cell carcinoma) AND (detection OR diagnosis) AND urine AND (biomarker OR assay). All studies had a minimum of 20 patients in both bladder cancer and control arms and reported sensitivity and/or specificity and/or receiver operating characteristics (ROC) curve. QUADAS-2 tool was used to assess risk of bias and applicability of studies. The search protocol was registered in the PROSPERO database (CRD42016049918). RESULTS: Systematic search yielded 115 reports were included for analysis. In single target biomarkers had a sensitivity of 2-94%, specificity of 46-100%, positive predictive value (PPV) of 47-100% and negative predictive value (NPV) of 21-94%. Multi-target biomarkers achieved a sensitivity of 24-100%, specificity of 48-100%, PPV of 42-95% and NPV of 32-100%. 50 studies achieved a sensitivity and specificity of ≥80%. Protein (n = 59) and transcriptomic (n = 21) biomarkers represents the most studied biomarkers. Multi-target biomarker panels had a better diagnostic accuracy compared to single biomarker targets. Urinary cytology with urinary biomarkers improved the diagnostic ability of the biomarker. The sensitivity and specificity of biomarkers were higher for primary diagnosis compared to patients in the surveillance setting. Most studies were case control studies and did not have a predefined threshold to determine a positive test result indicating a possible risk of bias. CONCLUSION: This comprehensive systematic review provides an update on urinary biomarkers of different 'omic' class and highlights promising biomarkers. Few biomarkers achieve a high sensitivity and negative predictive value. Such biomarkers will require external validation in a prospective observational setting before adoption in clinical practice.
Authors: Apurva Bhasin; Nicholas P Drago; Sudipta Majumdar; Emily C Sanders; Gregory A Weiss; Reginald M Penner Journal: Acc Chem Res Date: 2020-10-01 Impact factor: 24.466
Authors: Wei Shen Tan; Chin Hai Teo; Delcos Chan; Malgorzata Heinrich; Andrew Feber; Rachael Sarpong; Jennifer Allan; Norman Williams; Chris Brew-Graves; Chirk Jenn Ng; John D Kelly Journal: BJU Int Date: 2019-03-04 Impact factor: 5.588
Authors: Edward Cox; Pedro Saramago; John Kelly; Nuria Porta; Emma Hall; Wei Shen Tan; Mark Sculpher; Marta Soares Journal: Clin Genitourin Cancer Date: 2019-12-14 Impact factor: 2.872
Authors: Wei Shen Tan; Rachael Sarpong; Pramit Khetrapal; Simon Rodney; Hugh Mostafid; Joanne Cresswell; Dawn Watson; Abhay Rane; James Hicks; Giles Hellawell; Melissa Davies; Shalom J Srirangam; Louise Dawson; David Payne; Norman Williams; Chris Brew-Graves; Andrew Feber; John D Kelly Journal: BJU Int Date: 2018-08-29 Impact factor: 5.588