Screening for colorectal cancer. Stuart Taylor Consultant Radiologist University College Hospital

Transcription

1 Screening for colorectal cancer Stuart Taylor Consultant Radiologist University College Hospital

2 Topics Rationale for screening Screening methods CTC (+CAD) as a screening tool

3 Epidemiology 943,000 cases in 2000 & 510,000 deaths Highest N America, N Europe, Australasia Lowest in Sub-Saharan Africa, India Increasing in populations adopting Western lifestyle eg Chinese, Japan, East Europe Incidence stabilising in many countries eg UK & falling in US

4 Aetiology 60-70% sporadic 10-20% familial 5-10% specific genetic syndrome

5 Aetiology 60-70% sporadic 10-20% familial 5-10% specific genetic syndrome

6 Pathogenesis - Adenoma Carcinoma Sequence Most colorectal cancers arise from adenomatous polyps This progression may take up to 10 years in some people

7 Adenoma size Frequency of high grade dyplasia*: <5mm -0.9% 6-10mm -4.4% >10mm -16.2% May be the best practical measure of adenoma significance? *O'Brien MJ Gastroenterol 1990

8 Colorectal cancer screening

9 Pathogenesis - Adenoma Carcinoma Sequence Most colorectal cancers arise from adenomatous polyps This progression may take up to 10 years in some people

10 Cancer Staging and survival

11 Screening for colorectal cancer seems a good idea Common Precursor lesion Epidemiology well understood Proven treatments Prognosis improved with early detection

12 Many advocate screening from 50 to at least 74

13 How to screen Any test is a compromise between COST EFFICACY COMPLIANCE SAFETY

14 Screening Strategies One-Stage Screening Colonoscopy A Two-Stage Screening FOBT C Flex Sig. A DCBE C Virtual Colonoscopy A? Stool DNA Mutations C FOBT Faecal Occult Blood Test Flex Sig Flexible Sigmoidoscopy DCBE Double Contrast Barium Enema

15 Recommendations for screening

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17 FOBT cheap simple non invasive

18 Average stool blood concentrations

19 Unrehydrated Haemoccult High PPV for neoplasia - 50% For every 10 positives: 1 cancer 3 big adenomas 1 small adenoma 5 normal

20 Faecal Occult Blood Testing Cancers & large polyps bleed intermittently FOBT fails to detect 20-50% cancers & 80% polyps...but testing reduces mortality

21 Meta-analysis of FOBT screening trials: Towler et al BMJ 1998 Detects around 50% of cancer 16% reduction in CRC mortality; 23% for attendees

22 Colonoscopy?

23 Total colonoscopy? Whole colon (reference standard test) Cancer detection & polyp removal Magnification & chromo-endoscopy increase detection of advanced flat lesions Sedation (improve patient experience) Long screening interval-10years

24 Effects of Colonoscopic Polypectomy on Incidence of Colorectal Cancer Incidence *U.S. National Polyp Study 76 90% + Italian Multicenter Study Group 66% *Winawer, Zauber et al NEJM Citarda et al GUT 2001

25 Colonoscopy DCBE FSIG DCBE/FSIG Sensitivity for cancers (%) 97% 84% 97% (for 50% colon) 98% Specificity for cancers (%) 98% 97% 94% (for 50% colon) 98% Morbidity perforation haemorrhage (%) Mortality DCBE Double Contrast Barium Enema FSIG Flexible Sigmoidoscopy

26 Complications of total colonoscopy 3 per 100 polypectomies haemorrhage 3 per 1000 colonoscopies perforate 2 per 10,000 colonoscopies die

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28 Risks of Colonoscopy

29 Colonoscopy BSG audit of availability & quality of UK colonoscopy YES to investigate a positive Bowles, Williams et al Gut 2004 Unless there is a dramatic increase in primary test (eg FOBT) 9100 procedures, 230 colonoscopists,, 80 centres manpower and resources.a national screening programme would rapidly 76% total intubation using all criteria overburden already inadequate facilities Including RIF indentation! NO-as a primary screening test in UK and most of Europe 50% Five total fold intubation increase in using last 15 IC years valve Perforation Screening-1:769 1 extra (2/3 list non per interventional) DGH per Yes as a screening test in week US,Japan etc? Cause of death in 6

30 CT Colonography

31 Virtual Colonoscopy Patients take bowel prep +/- small volumes of oral contrast to label residual colonic contents Colon gently distended with gas Multi-slice (Helical) CT of the cleansed distended colon

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36 WHY CTC? Performance Safety Patient Preference

37 The ESGAR systematic review of CT colonography Steve Halligan 1,2, Doug Altman 2, Stuart Taylor 1, Sue Mallett 2, Wendy Atkin 3 Radiology 2006

38 Sensitivity: 92 5% (95% CI 72 8% to 98 3%) Study Pickhardt (2003) Yee (2001) Johnson (2003) Pineau (2003) Taylor (2003b) Bruzzi (2002) Wessling (2001) TP/(TP+FN) 62/72 49/49 30/47 18/20 9/10 5/5 3/ Sensitivity

39 Specificity 97 4%, (95% CI 95 1% to 98 6%) Study Pickhardt (2003) Yee (2001) Johnson (2003) Pineau (2003) Taylor (2003b) Bruzzi (2002) Wessling (2001) TN/(TN+FP) 1131/ / / /185 44/44 65/66 44/ Specificity

40 Sensitivity for cancer 95.9% (95% CI 91 4% to 98 5%). 144 of 150 Study Laghi (2002) Iannoaccone (2003) Fletcher (2000) Ginnerup (2003) Pineau (2003) Yee (2001) Morrin (2000) Spinzi (2001) Thomeer (2003) Mendelson (2000) Macari (2002) Taylor (2003b) Regge (2000) Fenlon (1999) Bruzzi (2002) Pickhardt (2003) Wessling (2001) TP/(TP+FN) 30/30 22/22 14/14 11/11 8/10 8/8 7/8 8/8 7/7 4/6 6/6 5/6 5/5 3/3 3/3 2/2 1/ Sensitivity

41 Benefits over existing techniques Quick (10 mins) Safe (although 10 UK reported perforations-no deaths)* (mortality rate with colonoscopy! ) Reduced prep Important extracolonic findings (5-10%)-good whole body test in polysymptomatic elderly *Burling D, Halligan S Slater A, Taylor S et al, Radiology 2005 (in press)

42 Significant Extra colonic findings Depends on the population Screening 10% Symptomatic 10-15% Elderly up to 20% Aortic aneurysm Metastasis Unsuspected malignancy eg renal Lung mass

43 Compliance CTC is less painful than colonoscopy and sigmoidoscopy* CTC better tolerated than endoscopy or barium enema* CTC preferred follow up test* *Taylor SA, Halligan S et al, AJR Sept 2003

44 Colonoscopy associated with adverse cardiovascular effects: (bradycardia/fall in BP/ventricular couplets)

45 Subtraction-cancer cancer Reduce Laxatives Zalis ME et al. Radiology :911-7.

46 CTC for screening

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48 Methods 1233 asymptomatic adults screening Mean age 58 yrs Same day CTC and colonoscopy Primary 3D endo-luminal read Segmental unblinding to enhance reference standard

49 Screening for colorectal neoplasia with virtual colonoscopy: results of a prospective multicentre trial in 1233 asymptomatic adults. Pickhardt et al. N Engl J Med Dec 4 th By-polyp sensitivity 6mm+ 8mm+ 10mm+ VC OC VC Virtual Colonoscopy OC Optical Colonoscopy

50 16mm malignant polyp missed at colonoscopy Colonoscopy has 6% miss rate for large lesions (>10mm) (Rex et al Gastroenterolgy 1997)

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52 NICE GUIDELINES

53 BUT.

54 Computed tomographic colonography: A multicentre comparison with standard colonoscopy for detection of colorectal neoplasia. Cotton et al. JAMA 2004:291; By-polyp sensitivity 6mm+ 8mm+ 10mm+ VC OC VC Virtual Colonoscopy OC Optical Colonoscopy

55 Analysis of air contrast barium enema, computed tomographic colonography, and colonoscopy: prospective comparison. Rockey et al. Lancet. 2005;365: patients By-polyp sensitivity 6mm+ 8mm+ 10mm+ CTC 51% 59% OC 99% 98% CTC Computed Tomographic Colonoscopy OC Optical Colonoscopy

56 Variability Likely related to Scan technology Bowel preparation, tagging Method of primary read It is clear that there is large interobserver variation with steep learning curve Perceptual error accounts for >50% missed lesions* *Fidler J, Fletcher J et al Acta Radiol 2004

57 Reader Training-evidence Taylor S, European Radiology 2003 Burling D, Radiology (in press) Spinzi Am J Gastro 2001 Clear Learning curve for CTC interpretation Training with 50 cases does not guarantee adequate performance Experts perform better than trained readers Fidler J, Acad Radiology 50% of missed lesion are errors of perception

58 Cancer detection vs observer group 40 CTC datasets Burling et al Radiology Observer Detected group (%) Experts (n=9) 92 Not detected (%) P (chi-sq) Radiologist s (n=10) Technician s (n=9) Radiologists vs Technicians p=0.87 ESGAR CT COLONOGRAPHY TRIAL

59 Computer Aided Diagnosis- Aims Automatically detects suspicious polyps & masses on CTC Increase radiologists diagnostic performance Decrease variably amongst readers Improve detection in screening programme (low incidence of pathology)

60 Computer assisted Diagnosis- Steps 1. Extract colon from CT dataset 2. Detection of polyp candidates-e.g. shape, curvature etc 3. Reduction of false positives-e.g. internal attenuation etc

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62 True positive

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66 False positives Complex folds Ileo-caecal valve Rectal tube Faecal residue Tagging-air interface Most rapidly dismissed by radiologist

67 False positive easily and rapidly dismissed

68 CAD performance Does NOT need to outperform experts Tends to be complementary to readers

69 Development of CAD Write a basic CAD algorithm Train the CAD on real polyps from endoscopically validated cases Test the CAD on a different set of endoscopically validated cases Test the effect of CAD on reader performance

70 CAD Products Several CAD products in development A few have achieved, or close to achieving, approval for clinical use. ColonCAD, Medicsight plc

71 VALIDATION

72 CT Colonography:Performance of Computer Assisted Reader Software for Polyp Detection in Comparison to Expert Observers S. Taylor, S. Halligan, D. Burling et al AJR March 2006

73 Methods-test test dataset 25 positive test datasets (13 tagged) (32 polyps>5mm) Independently read by each of 3 experts

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75 Results-detection 6-9mm (n=20) Experts (mean) 70% CAD 75% 10mm+ (n=12) Experts (mean) 92% CAD 92%

76 Conclusion CAD software at default settings has equivalent sensitivity to expert readers CAD is likely synergistic to expert readers

77 External validation CTC Data CTC Data Training Data Train Test Test Data

78 Study Aim: To determine the test characteristics of a trained CAD system using external validation

79 Methodology: External validation using Walter-Reed cases Downloaded from CT colonography training website National Library of Medicine; Walter Reed Army Medical Centre; National Cancer Institute

80 Results: Per-polyp sensitivity 29 of 31 (94%) 6mm + detected 9 of 10 (90%) 10mm + detected

81 Reader Performance

82 CT colonography: Assessment of Radiologist Performance With and Without Computer-Assisted Detection (CAD).

83 Study aim To determine whether CAD improves reader performance for CT colonography

84 Methods: Data sources Test set: 107 patients Polyps located by 3 experts with colonoscopic findings 60 with 142 polyps, 47 normal 14 patients 1cm+, 40 patients 6mm+

85 Methods: Observers 10 radiologists Fully-accredited in abdominal CT Non-expert at CTC

86 Methods: Reading paradigm 107 cases read by 10 radiologists 2-months temporal separation 107 cases read again With ColonCAD applied

87 Results: Per-patient sensitivity & specificity With CAD Sensitivity increased significantly in 70% readers Specificity decreased significantly in 10% readers

88 Change in sensitivity for 60 patients with polyps Change in sensitivity Readers

89 Effect of correct CAD prompting on polyp detection by readers

90 Polyps marked by computer: Increase in polyps detected for each reader L M S Polyp size Increase no polyps with aided read

91 Polyps not marked by computer: Increase in polyps detected for each reader Increase no polyps with aided read L M S Polyp size

92 Results: Overall With CAD 9 readers (90%) benefited by increased per-patient sensitivity &/or reduced reading time 4 (40%) readers benefited by both

93 Conclusions: CAD Significantly increases reader sensitivity Per-patient Per-polyp Has less impact on specificity Significantly reduces interpretation time

94 CT colonography (CTC): Investigation of the optimum reader paradigm using computer assisted detection (CAD) software SA Taylor, R Aslam, J Barlow, A Gupta, R Iannaccone, D Kim, P Lefere, E McFarland, C Miller, E Paulson, J Yee, S Charman S Halligan, M Roddie RADIOLOGY (IN PRESS)

95 Sensitivity (6mm+) Trained Experienced 6-9mm 10mm+ 6-9mm 10mm+ unassisted second concurrent

96 Overall conclusion CAD CAD shows good performance characteristics even when tested on external data CAD improves reader performance but does not remove the need for training

97 Conclusions II CRC screening makes biological sense & on the whole is cost effective Choice of screening modality depends on health economics, infrastructure, patient factors etc CTC (+CAD) viable screening option