The Queen Alexandra Hospital PORTSMOUTH, UK

Transcription

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2 DR NIGEL COWAN DM FRCP FRCR The Queen Alexandra Hospital PORTSMOUTH, UK

3 The development of diagnostic strategies for investigating haematuria with special focus on disease prevalence diagnostic accuracy risk factors and risk stratification

4 Diagnostic testing - 5 key pieces of information 1. What is the diagnostic question? 2. What is the probability the patient has the disease? 3.How accurate is the diagnostic test? 4. What is the optimum diagnostic strategy? 5. How will the test results affect patient s management? Adapted from Weinstein et al 2005 AJR Clinical evaluation of diagnostic tests

5 What is the diagnostic / clinical question? 1 Diagnostic question?

6 WHAT IS THE CAUSE OF HAEMATURIA?

7 Diagnostic testing - 5 key pieces of information 1. What is the diagnostic question? 2. What is the probability the patient has the disease? 3.How accurate is the diagnostic test? 4. What is the optimum diagnostic strategy? 5. How will the test results affect patient s management? Adapted from Weinstein et al 2005 AJR Clinical evaluation of diagnostic tests

8 What is the probability the patient has the disease? 2 Disease prevalence?

9 Definition of haematuria Visible haematuria Nonvisible haematuria either may indicate significant underlying disease

10 Results for disease prevalence n=1005 DISEASE Cowan et al 2012 % Khadra et al 1999 Edwards et al 2006 Bladder cancer Stones Renal cell cancer UT urothelial cancer % UTI Prostate cancer ADPKD Chronic pyelonephritis Nephrological disease No disease found

11 Prevalence of disease by age group and gender Age Group Men Number of patients UTUC RCC Stones Totals Women Totals Overall total

12 Diagnostic testing - 5 key pieces of information 1. What is the diagnostic question? 2. What is the probability the patient has the disease? 3.How accurate is the diagnostic test? 4. What is the optimum diagnostic strategy? 5. How will the test results affect patient s management? Adapted from Weinstein et al 2005 AJR Clinical evaluation of diagnostic tests

13 What is the diagnostic accuracy of the test? 3 Diagnostic accuracy?

14 Diagnostic accuracy Test Technique Interpretation

15 How do you assess the overall quality of a diagnostic test? 1. Diagnostic accuracy (Se, Sp, PPV, NPV, Acc) 2. Cost 3. Time 4. Patient acceptability 5. All of the above

16 US compared with CT urography for investigating haematuria Evaluation & comparison of US with CT urography for diagnosing upper urinary tract disease in a hospital haematuria rapid diagnosis clinic Tse et al ESUR 2010

17 CT urography compared with US for investigating haematuria Se Sp RCC UTUC Stone disease US 0.67 (2/3) 1.0 (97/97) CT 1.0 (3/3) 1.0 (97/97) US 0 (0/2) 1.0 (98/98) CT 1.0 (2/2) 0.99 (97/98) US 0.4 (8/20) 0.96 (7/173)

18 CT urography compared with US for investigating haematuria Se Sp RCC UTUC Stone disease US 0.67 (2/3) 1.0 (97/97) CT 1.0 (3/3) 1.0 (97/97) US 0 (0/2) 1.0 (98/98) CT 1.0 (2/2) 0.99 (97/98) US 0.4 (8/20) 0.96 (7/173)

19 CT urography compared with US for investigating haematuria Se Sp RCC UTUC Stone disease US 0.67 (2/3) 1.0 (97/97) CT 1.0 (3/3) 1.0 (97/97) US 0 (0/2) 1.0 (98/98) CT 1.0 (2/2) 0.99 (97/98) US 0.4 (8/20) 0.96 (7/173)

20 US compared with CT urography US has low sensitivity for upper tract cancers and stone disease, particularly for UTUC - small tumours without hydronephrosis / hydroureter CT urography should be the preferred examination for investigating these patients at high risk The role of US should be reviewed for investigating high risk haematuria patients Tse et al ESUR 2010

21 CT urography for diagnosing UTUC and bladder cancer NC COWAN DM 2014, available for free download Cowan, N. C. (2012) CT urography for hematuria Nat. Rev. Urol. doi: /nrurol

22 CT urography for diagnosing UTUC and bladder cancer NC COWAN DM 2014, available for free download Cowan, N. C. (2012) CT urography for hematuria Nat. Rev. Urol. doi: /nrurol

23 CT urography for diagnosing UTUC and bladder cancer NC COWAN DM 2014, available for free download Cowan, N. C. (2012) CT urography for hematuria Nat. Rev. Urol. doi: /nrurol

24 Results for the diagnostic accuracy of CT urography for UTUC and RCC in 1005 patients For CT urography for diagnosing upper urinary tract cancer using CIA software 95% CI by Wilson method: Se = 1.0 (95% CI 0.93 to 1.0) Sp = 0.98 (95% CI 0.97 to 0.99) PPV = 0.71 (95% CI 0.60 to 0.81) NPV = 1.0 (95% CI 0.99 to 1.0) Table 14

25 Diagnostic accuracy of CT urography for UTUC DISEASE +VE -VE +VE TP FP PPV = TEST -VE FN TN NPV = Se = Sp =

26 Diagnostic accuracy of CT urography for UTUC DISEASE +VE -VE +VE TP FP PPV = TEST -VE FN TN NPV = Se = Sp =

27 Diagnostic accuracy of CT urography for UTUC DISEASE +VE -VE +VE TP FP PPV = TEST -VE FN TN NPV = Se = Sp =

28 Diagnostic accuracy of CT urography for UTUC DISEASE +VE -VE +VE TP FP PPV = TEST -VE FN TN NPV = Se = Sp =

29 Diagnostic accuracy of CT urography for UTUC DISEASE +VE -VE +VE TP FP PPV = TEST -VE FN TN NPV = Se = Sp =

30 Diagnostic accuracy of CT urography for UTUC DISEASE +VE -VE +VE TP FP PPV = TEST -VE FN TN NPV = Se = Sp =

31 Identifying problems and finding solutions False positive diagnoses for UTUC Clot Debris Kink of the ureter Fibroepithelial polyp Injury to the ureter, passage of a stone, stent placement or ureteroscopy Ureteritis cystica Metastases (melanoma, RCC) Flow artefacts following furosemide Cauliflower papilla, a normal variant Amyloid Renal cell carcinoma Lymphoma Vascular impression Inflammation, fibrosis PPV = CT urography: over diagnosing UTUC biopsy

32 Technique

33 A recommended protocol for CT urography? UE URO/PV/ NG EX No iv CM s iv CM 750 s iv CM

34 A recommended protocol CT urography? Series Phase Position Coverage Target 1 Noncontrast Supine / Expiration K U B Stones 2 Urothelial/Nephrographic -phases s Supine / Expiration Abdomen and pelvis UUT Bladder Non GU 3 Excretory-phase 750 s Supine / Expiration K U B UUT Bladder 150 ml iv contrast 300 mg I / ml, single bolus*

35 Improved opacification scores lead to improved diagnostic accuracy Supine Prone Meindl et al Eur Radiol 2007, Experience with a biphasic excretory phase examination protocol

36 How is the technical quality of CT urography assessed? Opacification scoring: Collecting system 0, 1, 2 Abdominal ureter 0, 1, 2 Pelvic ureter 0, 1, 2 Bladder 0, 1, 2 (100 HU)

37 No manoeuvres, image at 540s, 50 ml x2 bolus

38 Image at 750 s, manoeuvres +ve, 150 ml, x1 bolus % CS Ab U Pel U Bladder Opacification Score 0-2 Collecting S Abdominal U Pelvic U Bladder

39 What manoeuvres may be used to improve the diagnostic accuracy of CT urography? 1 Pre-acquisition 2 During acquisition 3 Post-acquisition

40 What manoeuvres may be used to improve the diagnostic accuracy of CT urography? Pre-acquisition Oral water ml (iv fluid, furosemide) Empty bladder immediately before examination Remove belts, bras and shoes Exercise before excretory-phase (walk around CT machine, roll on table)

41 Which manoeuvres should I use? Bolus protocol 1 Single Indication Visible haematuria (patients at high risk for UTUC and RCC) 2 Double? 3 Triple Living related kidney donor assessment Percutaneous nephrolithotomy assessment

42 What manoeuvres may be used to improve the diagnostic accuracy of CT urography? x3 bolus Knox et al Eur Radiol 2010, Kekelidze et al 2010 Radiology

43 What manoeuvres may be used to improve the diagnostic accuracy of CT urography? During Acquire in expiration Isotropic acquisition

44 Acquire in expiration inspiration inspiration expiration

45 How do I set up for isotropic imaging? For isotropic voxels, set the RST to = pixel size PS = RFOV / MATRIX RFOV to give isotropic voxels = PS x Matrix = 0.75 x 512 = 384 mm 0.75 mm Mahesh 2002 Radiographics

46 What manoeuvres may be used to improve the diagnostic accuracy of CT urography? Post-acquisition Multiplanar reformat review Use a reporting template

47 Multiplanar reformat review (MPR) COR SAG COR SAG AX RECON AX RECON

48 NEW WAYS OF PRESENTING THE REPORT CT urography reporting template ID: History: Time Started: Time Finished: Opacification Score: R-CS R-AbU R-PelU (0,1,2) Disease Score: (0,1,2) Right Left Signs: Kidney Collecting System Abdominal Ureter R-HN / HU Y / N Pelvic Ureter L-CS Bladder L-AbU Lymphadenopathy Discussion: L-PelU Bones L-HN / HU Y / N Adrenals Bladder Other Disease Diagnosis 1 Diagnosis 2 Diagnosis 3

49 NEW WAYS OF PRESENTING THE REPORT CT urography reporting template 1. Upper tract 2. Bladder 3. Lymphadenopathy 4. Bones 5. Significant incidental disease

50 >50M, ex-smoker

51 78F, VH

52 79F, VH

53 69M, VH

54 69M, VH

55 69M, VH

56 What are the future developments to look out for? CT urography with earlier image acquisition

57 Important developments in CT Thinner sections More detector rows Faster acquisition times Acquire in many phases of contrast enhancement Dose reduction techniques

58 Phase development Nonenhanced Arterial Urothelial Portal venous Nephrographic Excretory Delayed excretory 0 s s 50 s 70 s 100 s s > 900 s

59 60-70 s references Kupershmidt AJR 2011; 197: Metser Radiology 2012; 264: Bladder Kim et al 2004 Radiology Park et al 2007 Radiology Jinzaki et al 2007 AJR Issues comparing optimised 60-70s acquisitions with suboptimal excretory-phase imaging

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62 73F, visible haematuria, CTU +ve

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70 Advantages Faster acquisition Greater patient throughput Cheaper More convenient for patient and staff Effect on diagnostic accuracy?

71 CT urography for diagnosis of UTUC: Are both nephrographic and excretory-phases necessary? NG-phase EX-phase NG+EX-phases R1 R2 R1 R2 R1 R2 Se Sp AUC Takeuchi et al 2015 AJR Conclusion - The nephrographic and excretory-phases are complimentary for the detection of UTUC

72 Diagnostic testing - 5 key pieces of information 1. What is the clinical question? 2. What is the probability the patient has the disease? 3.How accurate is the diagnostic test? 4. What is the optimum diagnostic strategy? 5. Will the test results affect the patient s management? Weinstein et al 2005 AJR Clinical evaluation of diagnostic tests

73 What is the optimum diagnostic strategy? 4 Diagnostic strategy?

74 What is the optimum diagnostic strategy? Order Test Disease Prevalence 1 Flexible cystoscopy Bladder cancer 19% 2 CT KUB noncontrast Stones 16% CT kidneys nephrographic-phase CT urography urothelial-phase CT urography excretory-phase 6 RUP/URS GBX UTUC 7 Rigid cystoscopy +/- Biopsy, TURBT Renal cell cancer 2% Upper tract urothelial cancer 2% UTUC, Bladder cancer Bladder cancer

75 Results for disease prevalence n=1005 DISEASE Cowan et al 2012 % Khadra et al 1999 Edwards et al 2006 Bladder cancer Stones Renal cell cancer UT urothelial cancer % UTI Prostate cancer ADPKD Chronic pyelonephritis Nephrological disease No disease found

76 Risk stratification for patients with haematuria Don t do all tests in all patients Reduces cost Reduces time to diagnosis Excretory-phase CT urography for investigating haematuria is now reserved for populations at high-risk for urothelial cancer following negative NC, URO, NG-phases

77 Risk stratification for haematuria (target tests to a specific disease) Visible or nonvisible Age < > 50 Smoking history Occupational exposure Family history Co-existing urothelial cancer Cystoscopy not possible Previous positive diagnostic imaging Positive urine cytology

78 Multivariable modelling. Results for the diagnostic accuracy of CT urography, flexible cystoscopy and voided urine cytology for diagnosing bladder cancer CTU as: Additional Test Replacement Test Triage Test Option 1 Triage Test Option 2 Voided Urine Cytology CTU & FC CTU FC CTU & / or FC CTU & / or FC 3 & 2 = +ve 1 = -ve, 3 & 2 = +ve 1 = -ve 3 & 2 = +ve 1 = -ve CTU: 3 = +ve, 2 & 1 = -ve FC: 3&2=+ve, 1=-ve CTU: 3=+ve, 2=equiv, 1=-ve FC: 3&2=+ve, 1=-ve 1-3 = -ve, 4 & 5 = +ve Se 1.0 (0.98 to 1.00) 0.95 (0.90 to 0.97) 0.98 (0.94 to 0.99) 1.0 (0.98 to 1.0) 0.95 (0.90 to 0.97) 0.38 (0.31 to 0.45) Sp 0.94 (0.91 to 0.95) 0.83 (0.80 to 0.86) 0.94 (0.92 to 0.96) 0.94 (0.91 to 0.95) 0.98 (0.97 to 0.99) 0.98 (0.96 to 0.99) PPV 0.80 (0.73 to 0.85) 0.58 (0.52 to 0.64) 0.80 (0.73 to 0.85) 0.80 (0.73 to 0.85) 0.93 (0.87 to 0.96) 0.82 (0.72 to 0.88) NPV Av no tests / patient 1.00 (0.99 to 1.00) 0.98 (0.97 to 0.99) 0.99 (0.99 to 1.0) 1.0 (0.99 to 1.0) 0.99 (0.97 to 0.99) 0.84 (0.81 to 0.87)

79 What is the optimum patient journey? Presentation Diagnosis by one diagnostic test Treatment

80 Diagnostic strategies H H H US-VE US+VE CT CT CT urography NC COWAN DM 2014, available for free download

81 Diagnostic imaging strategies for haematuria Visible haematuria CTU BIOPSY

82 Diagnostic strategies for investigating haematuria High risk for UTUC and RCC ( Risk score 3) Low risk for UTUC (Risk score < 3) High risk for RCC Low risk for tumour High risk for stones VH > 50 NVH > 50 VH < 50 NVH < 50 CT urography CT urography CT urography CT KUB UE UE NG EX-phases UE NG-phases UE NG-phases US KUB? FC FC FC FC? NC COWAN DM 2014, available for free download

83 Diagnostic strategies for investigating haematuria High risk for UTUC and RCC ( Risk score 3) Low risk for UTUC (Risk score < 3) High risk for RCC Low risk for tumour High risk for stones VH VH NVH NVH > 50 < 50 > 50 < 50 CT UROGRAPHY NC URO NG CT UROGRAPHY NC URO NG CT UROGRAPHY NC URO NG CT KUB NC FC FC FC FC NC COWAN DM 2014, available for free download

84 Diagnostic strategies for investigating haematuria High risk for UTUC and RCC ( Risk score 3) Low risk for UTUC (Risk score < 3) High risk for RCC Low risk for tumour High risk for stones VH VH NVH NVH > 50 < 50 > 50 < 50 CT UROGRAPHY NC URO NG FC CT UROGRAPHY NC URO NG FC NC COWAN DM 2014, available for free download

85 Diagnostic testing - 5 key pieces of information 1. What is the clinical question? 2. What is the probability the patient has the disease? 3.How accurate is the diagnostic test? 4. What is the optimum diagnostic strategy? 5. Will the test results affect the patient s management? Adapted from Weinstein et al 2005 AJR Clinical evaluation of diagnostic tests

86 How will the result of the test affect management? 5 Impact on management?

87 How will the result of the test affect management? % Role of Imaging BCa 19 Diagnosis, staging, avoid FC in 20% T2 from T3, NMIBC from MIBC Stone 16 Diagnosis, treatment planning, URS, ESWL, PCNL RCC 2 Diagnosis, staging, planning treatment, follow-up BX, RCC, ONCO, AML-fat UTUC 2 Diagnosis, staging, treatment planning, follow-up RNU, URS

88 Diagnostic testing - 5 key pieces of information 1. What is the clinical question? 2. What is the probability the patient has the disease? 3.How accurate is the diagnostic test? 4. What is the optimum diagnostic strategy? 5. How will the test results affect patient s management? Adapted from Weinstein et al 2005 AJR Clinical evaluation of diagnostic tests

89 Diagnostic testing - 5 key pieces of information 1. What is the clinical question? 2. What is the probability the patient has the disease? 3.How accurate is the diagnostic test? 4. What is the optimum diagnostic strategy? 5. How will the test results affect patient s management? Adapted from Weinstein et al 2005 AJR Clinical evaluation of diagnostic tests

90 Diagnostic testing - 5 key pieces of information 1. What is the clinical question? 2. What is the probability the patient has the disease? 3.How accurate is the diagnostic test? 4. What is the optimum diagnostic strategy? 5. How will the test results affect patient s management? Adapted from Weinstein et al 2005 AJR Clinical evaluation of diagnostic tests

91 Diagnostic testing - 5 key pieces of information 1. What is the clinical question? 2. What is the probability the patient has the disease? 3.How accurate is the diagnostic test? 4. What is the optimum diagnostic strategy? 5. How will the test results affect patient s management? Adapted from Weinstein et al 2005 AJR Clinical evaluation of diagnostic tests

92 Diagnostic testing - 5 key pieces of information 1. What is the clinical question? 2. What is the probability the patient has the disease? 3.How accurate is the diagnostic test? 4. What is the optimum diagnostic strategy? 5. How will the test results affect patient s management? Adapted from Weinstein et al 2005 AJR Clinical evaluation of diagnostic tests

93 Diagnostic testing - 5 key pieces of information 1. What is the clinical question? 2. What is the probability the patient has the disease? 3.How accurate is the diagnostic test? 4. What is the optimum diagnostic strategy? 5. How will the test results affect patient s management? Adapted from Weinstein et al 2005 AJR Clinical evaluation of diagnostic tests

94 THANK YOU