Does urinary cytology have a role in haematuria investigations?

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, DETECT I trial collaborators, A N Sridhar, B W Lamb, F Ocampo, H McBain, K Baillie, K Middleton, H Knight, S Maher, B Pathmanathan, A Harmathova, S Pelluri, J Pati, A Cossons, C Scott, S Madaan, S Bradfield, N Wakeford, Dann, J Cook, M Cornwell, R Mills, Thomas, S Reyner, G Vallejera, P Adeniran, S Masood, N Whotton, K Dent, S Pearson, J Hatton, M Newton, E Hheeney, K Green, S Evans, M Rogers, K Gupwell, S Ley, A Brown, J McGrath, N Lunt, P Hill, A Inclair, A Paredes-Guerra, B Holbrook, E Ong, H Wardle, D Wilson, A Bayles, R Fennelly, M Tribbeck, K Ames, J A Taylor, E Edmunds, J Moore, S Mckinley, T Nolan, A Peed, 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, A Rees, S Williams, S Dukes, A Goffe, R Mistry, J Chadwick, S Cocks, R Hull, A Oftus, Y Baird, S Moore, S Greenslade, J Margalef, I Chadbourn, M Harris, P Clitheroe, S Connolly, S Hodgkinson, H Haydock, E Storr, L Cogley, S Natale, W Lovegrove, K Slack, D Nash, K Smith, J Walsh, A M Guerdette, M Hill, 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, 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, DETECT I trial collaborators, A N Sridhar, B W Lamb, F Ocampo, H McBain, K Baillie, K Middleton, H Knight, S Maher, B Pathmanathan, A Harmathova, S Pelluri, J Pati, A Cossons, C Scott, S Madaan, S Bradfield, N Wakeford, Dann, J Cook, M Cornwell, R Mills, Thomas, S Reyner, G Vallejera, P Adeniran, S Masood, N Whotton, K Dent, S Pearson, J Hatton, M Newton, E Hheeney, K Green, S Evans, M Rogers, K Gupwell, S Ley, A Brown, J McGrath, N Lunt, P Hill, A Inclair, A Paredes-Guerra, B Holbrook, E Ong, H Wardle, D Wilson, A Bayles, R Fennelly, M Tribbeck, K Ames, J A Taylor, E Edmunds, J Moore, S Mckinley, T Nolan, A Peed, 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, A Rees, S Williams, S Dukes, A Goffe, R Mistry, J Chadwick, S Cocks, R Hull, A Oftus, Y Baird, S Moore, S Greenslade, J Margalef, I Chadbourn, M Harris, P Clitheroe, S Connolly, S Hodgkinson, H Haydock, E Storr, L Cogley, S Natale, W Lovegrove, K Slack, D Nash, K Smith, J Walsh, A M Guerdette, M Hill, 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

Abstract

Objectives: To determine the diagnostic accuracy of urinary cytology to diagnose bladder cancer and upper tract urothelial cancer (UTUC) as well as the outcome of patients with a positive urine cytology and normal haematuria investigations in patients in a multicentre prospective observational study of patients investigated for haematuria.

Patient and methods: The DETECT I study (clinicaltrials.gov NCT02676180) recruited patients presenting with haematuria following referral to secondary case at 40 hospitals. All patients had a cystoscopy and upper tract imaging (renal bladder ultrasound [RBUS] and/ or CT urogram [CTU]). Patients, where urine cytology were performed, were sub-analysed. The reference standard for the diagnosis of bladder cancer and UTUC was histological confirmation of cancer. A positive urine cytology was defined as a urine cytology suspicious for neoplastic cells or atypical cells.

Results: Of the 3 556 patients recruited, urine cytology was performed in 567 (15.9%) patients from nine hospitals. Median time between positive urine cytology and endoscopic tumour resection was 27 (IQR: 21.3-33.8) days. Bladder cancer was diagnosed in 39 (6.9%) patients and UTUC in 8 (1.4%) patients. The accuracy of urinary cytology for the diagnosis of bladder cancer and UTUC was: sensitivity 43.5%, specificity 95.7%, positive predictive value (PPV) 47.6% and negative predictive value (NPV) 94.9%. A total of 21 bladder cancers and 5 UTUC were missed. Bladder cancers missed according to grade and stage were as follows: 4 (19%) were ≥ pT2, 2 (9.5%) were G3 pT1, 10 (47.6%) were G3/2 pTa and 5 (23.8%) were G1 pTa. High-risk cancer was confirmed in 8 (38%) patients. There was a marginal improvement in sensitivity (57.7%) for high-risk cancers. When urine cytology was combined with imaging, the diagnostic performance improved with CTU (sensitivity 90.2%, specificity 94.9%) superior to RBUS (sensitivity 66.7%, specificity 96.7%). False positive cytology results were confirmed in 22 patients, of which 12 (54.5%) had further invasive tests and 5 (22.7%) had a repeat cytology. No cancer was identified in these patients during follow-up.

Conclusions: Urine cytology will miss a significant number of muscle-invasive bladder cancer and high-risk disease. Our results suggest that urine cytology should not be routinely performed as part of haematuria investigations. The role of urine cytology in select cases should be considered in the context of the impact of a false positive result leading to further potentially invasive tests conducted under general anaesthesia.

Keywords: #BladderCancer; #blcsm; #utuc; biomarker; cytology; diagnosis; haematuria; investigations; urine.

© 2018 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.

Figures

Figure 1
Figure 1
Flow diagram of patients recruited into study.

References

    1. Papanicolaou GN, Marshall VF. Urine sediment smears as a diagnostic procedure in cancers of the urinary tract. Science 1945; 101: 519–20
    1. Lotan Y, Roehrborn CG. Sensitivity and specificity of commonly available bladder tumor markers versus cytology: results of a comprehensive literature review and meta‐analyses. Urology 2003; 61: 109–18
    1. Bastacky S, Ibrahim S, Wilczynski SP, Murphy WM. The accuracy of urinary cytology in daily practice. Cancer 1999; 87: 118–28
    1. NICE. Bladder cancer: diagnosis and management of bladder cancer . BJU Int 2017; 120: 755‐65
    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. Dec; 188: 2473–81
    1. Tan WS, Feber A, Dong L et al. DETECT I & DETECT II: a study protocol for a prospective multicentre observational study to validate the UroMark assay for the detection of bladder cancer from urinary cells. BMC Cancer 2017. Nov; 15: 767
    1. Kelly JD, Fawcett DP, Goldberg LC. Assessment and management of non‐visible haematuria in primary care. BMJ 2009; 16: a3021–a3021
    1. Humphrey PA, Moch H, Cubilla AL, Ulbright TM, Reuter VE. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs‐Part B: prostate and Bladder Tumours. Eur Urol 2016; 70: 106–19
    1. Babjuk M, Bohle A, Burger M et al. EAU Guidelines on Non‐Muscle‐invasive Urothelial Carcinoma of the Bladder: update 2016. Eur Urol 2017; 71: 447–61
    1. Rosenthal DL, Wojcik EM, Kurtycz DF. The Paris system for reporting urinary cytology. New York, NY: Springer, 2016.
    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: 10–4
    1. Tan WS, Sarpong R, Khetrapal P et al. Can renal and bladder ultrasound replace CT urogram in patients investigated for microscopic hematuria? J Urol 2018. [Epub ahead of print]. 10.1016/j.juro.2018.04.065
    1. Hofland CA, Mariani AJ. Is cytology required for a hematuria evaluation? J Urol 2004; 171: 324–6
    1. Mishriki SF, Aboumarzouk O, Vint R, Grimsley SJ, Lam T, Somani B. Routine urine cytology has no role in hematuria investigations. J Urol 2013; 189: 1255–8
    1. Wollin T, Laroche B, Psooy K. Canadian guidelines for the management of asymptomatic microscopic hematuria in adults. Can Urol Assoc J. 2009; 3: 77–80
    1. Anderson J, Fawcett D, Feehally J et al. Joint consensus statement on the initial assessment of haematuria. BAUS/RA Guidelines. 2008; 2008: 1–5
    1. Spiess PE, Agarwal N, Bangs R et al. Bladder Cancer, Version 5.2017, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 2017; 15: 1240–67
    1. Horie S, Ito S, Okada H et al. Japanese guidelines of the management of hematuria 2013. Clin Exp Nephrol 2014; 18: 679–89
    1. van der Molen AJ, Hovius MC. Hematuria: a problem‐based imaging algorithm illustrating the recent Dutch guidelines on hematuria. AJR Am J Roentgenol 2012; 198: 1256–65
    1. Tan WS, Rodney S, Lamb B, Feneley M, Kelly J. Management of non‐muscle invasive bladder cancer: a comprehensive analysis of guidelines from the United States. Europe and Asia. Cancer treatment reviews. 2016; 47: 22–31
    1. Budman LI, Kassouf W, Steinberg JR. Biomarkers for detection and surveillance of bladder cancer. Can Urol Assoc J. 2008; 2: 212–21
    1. Koss LG, Deitch D, Ramanathan R, Sherman AB. Diagnostic value of cytology of voided urine. Acta Cytol 1985; 29: 810–6
    1. Planz B, Jochims E, Deix T, Caspers HP, Jakse G, Boecking A. The role of urinary cytology for detection of bladder cancer. Eur J Surg Oncol 2005; 31: 304–8
    1. Owens CL, Vandenbussche CJ, Burroughs FH, Rosenthal DL. A review of reporting systems and terminology for urine cytology. Cancer Cytopathol. 2013; 121: 9–14
    1. Raitanen MP, Aine R, Rintala E et al. Differences between local and review urinary cytology in diagnosis of bladder cancer. An interobserver multicenter analysis. Eur Urol. 2002; 41: 284–9
    1. Brimo F, Vollmer RT, Case B, Aprikian A, Kassouf W, Auger M. Accuracy of urine cytology and the significance of an atypical category. Am J Clin Pathol 2009; 132: 785–93
    1. Muus Ubago J, Mehta V, Wojcik EM, Barkan GA. Evaluation of atypical urine cytology progression to malignancy. Cancer Cytopathol. 2013; 121: 387–91
    1. Mowatt G, Zhu S, Kilonzo M et al. Systematic review of the clinical effectiveness and cost‐effectiveness of photodynamic diagnosis and urine biomarkers (FISH, ImmunoCyt, NMP22) and cytology for the detection and follow‐up of bladder cancer. Health Technol Assess 2010; 14: 1–331
    1. Chang SS, Boorjian SA, Chou R et al. Diagnosis and treatment of non‐muscle invasive bladder cancer: AUA/SUO guideline. J Urol 2016; 196: 1021–9
    1. Blick CG, Nazir SA, Mallett S et al. Evaluation of diagnostic strategies for bladder cancer using computed tomography (CT) urography, flexible cystoscopy and voided urine cytology: results for 778 patients from a hospital haematuria. BJU Int 2012; 110: 84–94
    1. Gopalakrishna A, Fantony JJ, Longo TA et al. Anticipatory Positive Urine Tests for Bladder Cancer. Ann Surg Oncol 2017; 24: 1747–53
    1. Tan WS, Tan WP, Tan MY et al. Novel urinary biomarkers for the detection of bladder cancer: a systematic review. Cancer Treat Rev 2018; 69: 39–52

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe