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

W S Tan, A Ahmad, A Feber, H Mostafid, J Cresswell, C D Fankhauser, S Waisbrod, T Hermanns, P Sasieni, J D Kelly, 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, W S Tan, A Ahmad, A Feber, H Mostafid, J Cresswell, C D Fankhauser, S Waisbrod, T Hermanns, P Sasieni, J D Kelly, 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

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.

Conflict of interest statement

None reported.

© 2018 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.

Figures

Figure 1
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
Figure 2
Estimated probability of bladder cancer by age, type of haematuria and smoking history for male (a) and female (b).

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