. 2019 Apr;285(4):436-445.

doi: 10.1111/joim.12868. Epub 2019 Jan 4.

Development and validation of a haematuria cancer risk score to identify patients at risk of harbouring cancer

W S Tan^{1

2}, A Ahmad³, A Feber^{1

4}, H Mostafid⁵, J Cresswell⁶, C D Fankhauser⁷, S Waisbrod⁷, T Hermanns⁷, P Sasieni⁸, J D Kelly^{1

2}; DETECT I trial collaborators

Collaborators, Affiliations

Collaborators

DETECT I trial collaborators:
P Khetrapal, H Baker, A N Sridhar, B W Lamb, F Ocampo, H McBain, K Baillie, K Middleton, D Watson, H Knight, S Maher, A Rane, B Pathmanathan, A Harmathova, G Hellawell, S Pelluri, J Pati, A Cossons, C Scott, S Madaan, S Bradfield, N Wakeford, A Dann, J Cook, M Cornwell, R Mills, S Thomas, S Reyner, G Vallejera, P Adeniran, S Masood, N Whotton, K Dent, S Pearson, J Hatton, M Newton, E Heeney, K Green, S Evans, M Rogers, K Gupwell, S Whiteley, A Brown, J McGrath, N Lunt, P Hill, A Sinclair, A Paredes-Guerra, B Holbrook, E Ong, H Wardle, D Wilson, A Bayles, R Fennelly, M Tribbeck, K Ames, M Davies, J A Taylor, E Edmunds, J Moore, S Mckinley, T Nolan, A Speed, A Tunnicliff, G Fossey, A Williams, M George, I Hutchins, R Einosas, A Richards, A Henderson, B Appleby, L Kehoe, L Gladwell, S Drakeley, J A Davies, R Krishnan, H Roberts, C Main, S Jain, J Dumville, N Wilkinson, J Taylor, F Thomas, K Goulden, C Vinod, E Green, C Waymont, J Rogers, A Grant, V Carter, H Heap, C Lomas, P Cooke, L Scarratt, T Hodgkiss, D Johnstone, J Johnson, J Allsop, J Rothwell, K Connolly, J Cherian, S Ridgway, M Coulding, H Savill, J Mccormick, M Clark, G Collins, K Jewers, S Keith, G Bowen, J Hargreaves, K Riley, S Srirangam, A Rees, S Williams, S Dukes, A Goffe, L Dawson, R Mistry, J Chadwick, S Cocks, R Hull, A Loftus, Y Baird, S Moore, S Greenslade, J Margalef, I Chadbourn, M Harris, J Hicks, P Clitheroe, S Connolly, S Hodgkinson, H Haydock, A Sinclair, E Storr, L Cogley, S Natale, W Lovegrove, K Slack, D Nash, K Smith, J Walsh, A M Guerdette, M Hill, D Payne, B Taylor, E Sinclair, M Perry, M Debbarma, D Hewitt, R Sriram, A Power, J Cannon, L Devereaux, A Thompson, K Atkinson, L Royle, J Madine, K MacLean, R Sarpong, C Brew-Graves, N Williams

Affiliations

¹ Division of Surgery & Interventional Science, University College London, London, UK.
² Department of Urology, University College London Hospital, London, UK.
³ Cancer Intelligence, Cancer Research UK, London, UK.
⁴ UCL Cancer Institute, London, UK.
⁵ Department of Urology, Royal Surrey County Hospital, Guildford, UK.
⁶ Department of Urology, James Cook University Hospital, Middlesbrough, UK.
⁷ Department of Urology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁸ Faculty of Life Sciences & Medicine, School of Cancer & Pharmaceutical Sciences, Innovation Hub, Guys Cancer Centre, Guys Hospital, King's College London, London, UK.

PMID: 30521125
PMCID: PMC6446724
DOI: 10.1111/joim.12868

Development and validation of a haematuria cancer risk score to identify patients at risk of harbouring cancer

W S Tan et al. J Intern Med. 2019 Apr.

. 2019 Apr;285(4):436-445.

doi: 10.1111/joim.12868. Epub 2019 Jan 4.

Authors

W S Tan^{1

2}, A Ahmad³, A Feber^{1

4}, H Mostafid⁵, J Cresswell⁶, C D Fankhauser⁷, S Waisbrod⁷, T Hermanns⁷, P Sasieni⁸, J D Kelly^{1

2}; DETECT I trial collaborators

Collaborators

DETECT I trial collaborators:
P Khetrapal, H Baker, A N Sridhar, B W Lamb, F Ocampo, H McBain, K Baillie, K Middleton, D Watson, H Knight, S Maher, A Rane, B Pathmanathan, A Harmathova, G Hellawell, S Pelluri, J Pati, A Cossons, C Scott, S Madaan, S Bradfield, N Wakeford, A Dann, J Cook, M Cornwell, R Mills, S Thomas, S Reyner, G Vallejera, P Adeniran, S Masood, N Whotton, K Dent, S Pearson, J Hatton, M Newton, E Heeney, K Green, S Evans, M Rogers, K Gupwell, S Whiteley, A Brown, J McGrath, N Lunt, P Hill, A Sinclair, A Paredes-Guerra, B Holbrook, E Ong, H Wardle, D Wilson, A Bayles, R Fennelly, M Tribbeck, K Ames, M Davies, J A Taylor, E Edmunds, J Moore, S Mckinley, T Nolan, A Speed, A Tunnicliff, G Fossey, A Williams, M George, I Hutchins, R Einosas, A Richards, A Henderson, B Appleby, L Kehoe, L Gladwell, S Drakeley, J A Davies, R Krishnan, H Roberts, C Main, S Jain, J Dumville, N Wilkinson, J Taylor, F Thomas, K Goulden, C Vinod, E Green, C Waymont, J Rogers, A Grant, V Carter, H Heap, C Lomas, P Cooke, L Scarratt, T Hodgkiss, D Johnstone, J Johnson, J Allsop, J Rothwell, K Connolly, J Cherian, S Ridgway, M Coulding, H Savill, J Mccormick, M Clark, G Collins, K Jewers, S Keith, G Bowen, J Hargreaves, K Riley, S Srirangam, A Rees, S Williams, S Dukes, A Goffe, L Dawson, R Mistry, J Chadwick, S Cocks, R Hull, A Loftus, Y Baird, S Moore, S Greenslade, J Margalef, I Chadbourn, M Harris, J Hicks, P Clitheroe, S Connolly, S Hodgkinson, H Haydock, A Sinclair, E Storr, L Cogley, S Natale, W Lovegrove, K Slack, D Nash, K Smith, J Walsh, A M Guerdette, M Hill, D Payne, B Taylor, E Sinclair, M Perry, M Debbarma, D Hewitt, R Sriram, A Power, J Cannon, L Devereaux, A Thompson, K Atkinson, L Royle, J Madine, K MacLean, R Sarpong, C Brew-Graves, N Williams

Affiliations

¹ Division of Surgery & Interventional Science, University College London, London, UK.
² Department of Urology, University College London Hospital, London, UK.
³ Cancer Intelligence, Cancer Research UK, London, UK.
⁴ UCL Cancer Institute, London, UK.
⁵ Department of Urology, Royal Surrey County Hospital, Guildford, UK.
⁶ Department of Urology, James Cook University Hospital, Middlesbrough, UK.
⁷ Department of Urology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
⁸ Faculty of Life Sciences & Medicine, School of Cancer & Pharmaceutical Sciences, Innovation Hub, Guys Cancer Centre, Guys Hospital, King's College London, London, UK.

PMID: 30521125
PMCID: PMC6446724
DOI: 10.1111/joim.12868

Abstract

Background: A lack of consensus exists amongst national guidelines regarding who should be investigated for haematuria. Type of haematuria and age-specific thresholds are frequently used to guide referral for the investigation of haematuria.

Objectives: To develop and externally validate the haematuria cancer risk score (HCRS) to improve patient selection for the investigation of haematuria.

Methods: Development cohort comprise of 3539 prospectively recruited patients recruited at 40 UK hospitals (DETECT 1; ClinicalTrials.gov: NCT02676180) and validation cohort comprise of 656 Swiss patients. All patients were aged >18 years and referred to hospital for the evaluation of visible and nonvisible haematuria. Sensitivity and specificity of the HCRS in the validation cohort were derived from a cut-off identified from the discovery cohort.

Results: Patient age, gender, type of haematuria and smoking history were used to develop the HCRS. HCRS validation achieves good discrimination (AUC 0.835; 95% CI: 0.789-0.880) and calibration (calibration slope = 1.215) with no significant overfitting (P = 0.151). The HCRS detected 11.4% (n = 8) more cancers which would be missed by UK National Institute for Health and Clinical Excellence guidelines. The American Urological Association guidelines would identify all cancers with a specificity of 12.6% compared to 30.5% achieved by the HCRS. All patients with upper tract cancers would have been identified.

Conclusion: The HCRS offers good discriminatory accuracy which is superior to existing guidelines. The simplicity of the model would facilitate adoption and improve patient and physician decision-making.

Keywords: bladder cancer; detection; haematuria; nomogram; predict; urinary tract cancer.

PubMed Disclaimer

Conflict of interest statement

None reported.

Figures

**Figure 1**
ROC curve of the haematuria cancer risk score. AUC 0.768 (95% CI: 0.741, 0.795) in the development cohort and AUC 0.835 (95% CI: 0.789, 0.880) in the validation cohort. The white square, circle and triangle give 0.972 (95% CI: 0.954, 0.989), 0.951 (95% CI: 0.923, 0.975) and 0.898 (95 %CI: 0.863, 0.930) sensitivity in the development data set with cut‐off values of 4.015, 4.386 and 4.916, respectively. Using the same cut‐off values, the black square, circle and triangle show 0.986 (95% CI: 0.957, 1.000), 0.943 (95% CI: 0.886, 0.986) and 0.857 (95% CI: 0.771, 0.929) sensitivity in the validation data set, respectively.

**Figure 2**
Estimated probability of bladder cancer by age, type of haematuria and smoking history for male (a) and female (b).

See this image and copyright information in PMC

References

1. Linder BJ, Bass EJ, Mostafid H, Boorjian SA. Guideline of guidelines: asymptomatic microscopic haematuria. BJU Int 2017; 16: 14016. - PubMed
1. National Institute for Health and Care Excellence . Suspected cancer: recognition and referral. 2015. - PubMed
1. Davis R, Jones JS, Barocas DA et al Diagnosis, evaluation and follow‐up of asymptomatic microhematuria (AMH) in adults: AUA guideline. J Urol 2012; 188: 2473–81. - PubMed
1. Tan WS, Feber A, Sarpong R et al Who Should Be Investigated for Haematuria? Results of a Contemporary Prospective Observational Study of 3556 Patients. Eur Urol 2018; 74: 10–14. - PubMed
1. Iasonos A, Schrag D, Raj GV, Panageas KS. How to build and interpret a nomogram for cancer prognosis. J Clin Oncol 2008; 26: 1364–70. - PubMed

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Development and validation of a haematuria cancer risk score to identify patients at risk of harbouring cancer

Collaborators

Affiliations

Development and validation of a haematuria cancer risk score to identify patients at risk of harbouring cancer

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

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References

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