Bowel Cancer Screening Exploiting science brings better medicine

Transcription

1 Camberley & District Bowel Cancer Screening Exploiting science brings better medicine Prof Stephen P. Halloran

2 World - All Cancers Men Incidence & Mortality (2012) Women Incidence Mortality GLOBOCAN 2012 (IARC) Estimated age-standardised rates/100,000

3 World Top 20 Cancers Men 1 Incidence & Mortality (2012) Women World - Bowel Cancer 3 rd commonest cancer 4 nd cause of Ca deaths Western Europe 2 nd commonest cancer death 2 nd commonest cancer 1 st commonest cancer in non-smoking men? GLOBOCAN 2012 (IARC) Estimated age-standardised rates/100,000

4 W. Europe Top 20 Cancers Men Incidence & Mortality (2012) Women 2 1 World - Bowel Cancer 3 rd commonest cancer 4 nd cause of Ca deaths Incidence Mortality Western Europe 3 nd commonest cancer 2 nd commonest cancer death 1 st commonest cancer in non-smoking men? GLOBOCAN 2012 (IARC) Estimated age-standardised rates/100,000

5 Bowel Cancer Incidence & Mortality (2012) Uruguay

6 Bowel Cancer Incidence & Mortality (2012)

7 % Change Incidence % Change Mortality % Change over 10 year in CRC Incidence & Mortality Arnold M, et al. Gut 2016;0:1 9

8 Total cancer deaths (millions) Deaths From Cancer Low - Middle Income Countries 12 High Income Countries

9 UK Bowel Cancer age at diagnosis Europe in 14 men 1 in 19 women Diagnosed bowel cancer during their lifetime Diagnosed - 447,000 p.a. Die - 215,000 p.a. 83% in >60 years 94% in >50 years

10 Bowel Cancer Genetic Risk Two well described genetic conditions FAP - Familial adenomatous polyposis 1% of all bowel cancer - (auto rec. /dom) 100% risk by age s of polyps) mutation Lynch Syndrome - HNPCC Hereditary non-polyposis colorectal cancer 2-7% of all bowel cancer (and other cancers) 40% risk by age 30, MSH2, and MSH6 (autosomal dominant) 1 st degree relative diagnosed with bowel cancer <50y

11 Diet and Exercise Red & processed meat Overweight Alcohol Low fibre diet Lack of exercise Low fruit & vegetable diet Smoking Bowel Cancer Risk Factors Responsible for 21% of all bowel cancers Responsible for 19% of all cancers Other Previous bowel cancer Diabetes Severe ulcerative colitis Crohn s disease Ashkenazi Jewish Family history Deprivation

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13 WHO Criteria for Screening The condition is an important health problem 2. Its natural history is well understood 3. It is recognisable at an early stage 4. Treatment is better at an early stage 5. A suitable test exists 6. An acceptable test exists 7. Adequate facilities exist to cope with abnormalities detected 8. Screening is done at repeated intervals when the onset is insidious 9. The chance of harm is less than the chance of benefit 10. The cost is balanced against benefit

14 Colorectal Cancer Pathogenesis Case for Screening Cancer Stage Screening Colonoscopy 30 to 45 mins 1 Look for polyps 2 remove (polypectomy) 3 4 Look for cancers surgery Polyp >50 years old - 1 in 4 have polyps 1 in 10 change to invasive cancer Alive - 5 years after treatment 93% 77% 48% 7% 10 years

15 20-15 years ago Large Randomised Controlled Trials FOBT Colorectal Cancer Screening Minnesota Nottingham Funen France Amongst those who did the tests 23% reduction in mortality Overall 16% reduction in mortality

16 Colorectal cancer screening: An updated review of the available options Iyad A Issa, Malak Noureddine World J Gastroenterol 2017 July 28; 23(28): FOBt is still the most appropriate screening test'

17 England Bowel Cancer Screening 1. Day 1 Pre-invitation to be screened + literature 2. Day 8 By default - stool collection kit (Free return post) 3. Day 30 Reminder 4. and then a. No 3m repeat invitation in 2 years b. Kit Negative repeat in 2 years c. Kit Positive Hub. i. Makes nurse (SSP) appointment (5 days time) ii. Notify GP (first class mail) iii. Assessed for colonoscopy

18 England BCSP gfobt timeline Start 2 yearly Screening Cycle D1 Invitation Kit & Spatula Return Envelope D8 <2d +ve Result Patient & GP Letter Kit Read (1)d SSP Clinic Appointment <14d <14d D29 M3 Screening Colonoscopy Surveillance Colonoscopy 2 Years Pre-Invitation At Screening Due Date Kit Returned -ve Result Patient letter & GP letter /e-message Reminder Letter No Response GP Letter/ E-Comms Next Pre-Invitation Freephone Helpline (

19 Easy access to Information Access to Information Emphasis on reaching everyone!

20 20% 18% 2% 2% 2% 6% 7% 9% 8% 8% England Screening Outcomes Episode 1, 2 & /12 17% 10% 11% Cancer detected High-risk adenoma 0% 0% 1% 1 st Episode (Prevalent) 2 nd Episode (Incident) 17% 13% Intermediate-risk adenoma Low-risk adenoma Abnormal finding Abnormal, no histology 3 rd Episode (Incident) 28% Normal result No result 27% 31% 16% 21% 26% Polypectomy Rate 48%

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22 % Uptake % Uptake - gfobt Screening (Southern Hub - Population year) % Uptake in all invited % Uptake following previous acceptance 61% Uptake % Uptake following previous refusal Date Sept 2006 April 2013

23 % Uptake Relationship to Socioeconomic Status First 2.6 million Invitation (BCSP - UCL Study) Male Female von Wagner C, Baio G, Raine R et al. (2011) Int J Epidemiol 40,

24 % Uptake FOBT kits First 2.6 million invitations in England von Wagner C, Baio G, Raine R et al. (2011) Int J Epidemiol 40,

25 %Uptake of FOBt screening in different ethnic groups in the Netherlands Ethnic Dutch Other Western Surinamese & Antillean S & E Asian 40 Middle & Central East African % Uptake Ethnic Dutch Other Western Surinamese & Antillean Uptake of faecal occult blood test colorectal cancer screening by different ethnic groups in the Netherlands M. Deutekom E J of Public Health 2009 Vol. 19, No. 4, S & E Asian Middle & Central East African

26 1 st Invitation 2 nd Invitation 3 rd Invitation Very Poor Adherence Poor Adherence Full Adherence % Uptake - 3 Episodes (E1, E2 & E3) BCSP Southern Hub Colorectal cancer screening uptake over three biennial invitation rounds in the English bowel cancer screening programme. Lo SH, Halloran et al Gut Adherence to screening? 70% 1 of 3 61% 2 of 3 44% 3 of st Episode 2nd Episode 3rd Episode At least once At least twice At least 3 times

27 Small effect (0.7%) on Uptake Socioeconomic gradient 1. Impact of general practice endorsement on the social gradient in uptake in bowel cancer screening Raine R, et al. BRITISH JOURNAL OF CANCER 114(3): Effects of evidence-based strategies to reduce the socioeconomic gradient of uptake in the English NHS Bowel Cancer Screening Programme (ASCEND): four cluster-randomised controlled trials Wardle J, et al. LANCET 387(10020): Colorectal cancer screening uptake over three biennial invitation rounds in the English bowel cancer screening programme Lo SH, et al. 2nd Digestive-Disorders-Fed. Conf., London,, GUT. BMJ. 64: A373-A

28 Faecal Occult Blood Tests FIT Haemoglobin - Haem Globin Antibody Haem (containing recognition iron) of the tertiary Release structure of oxygen produced from H 2 Oby 2 the folding Oxidise of a the dye amino (guaiac) acid chain in the globin protein. Change in colour (blue) gfobt Haem Guaiac test gfobt Globin Immunochemical ifobt (FIT)

29 In good company! European guidelines for quality assurance in colorectal cancer screening and diagnosis. Chapter 4. Faecal occult blood testing. Halloran SP, Launoy G, Zappa M Endoscopy 2012; 44 (S 03):SE65-SE87

30 What is the Faecal Immunochemical Test? Globin Protein structure.. Unique to the humans Haem Contains iron Hb

31 What is the Faecal Immunochemical Test? Making the Test Reagents 1. Antibodies prepared against 2. human haemoglobin (just the globin) Hb

32 What is the Faecal Immunochemical Test? Test Reagents + = Anti-human Hb antibodies Particles of a latex polymer (e.g. polystyrene) Latex coated with anti-human Hb immunoglobulin

33 What is the Faecal Immunochemical Test? + = Latex particles coated with anti-hb antibodies Blood in faeces (human haemoglobin) Latex bound antibody-hb complexes

34 What is the Faecal Immunochemical Test? Light source wavelength nm Particles cross link and block the passage of light The reduction in light intensity relates to Hb Glass or plastic container (cuvette) concentration Immunoturbidimetric analysis Light measurement Photometer

35 Individual analyser results nghb/ml UK FIT Pilot 150 samples 600 individual measurements 5 Batches each of 30 samples, 4 analysers, 2 sites over 7 months April October y=x Line of best fit y=0.997x Mean result of 4 analysers nghb/ml

36 Midlands & North West Hub More Deprivation Population 13.1 m gfobt Kits = 537,770 FIT Kits = 19,289 FIT Pilot 2014/5 (England) Both Hubs Population 27.8 m gfobt Kits = 1,126,087 FIT Kits = 40,930 Southern Hub Less Deprivation Population 14.7 m gfobt Kits = 588,317 FIT Kits = 21,641 FIT Pilot FIT Pilot

37 Uptake & All Episodes 2014 Southern, Midlands & NW Pilot Both 0 5 previous screening invitations 7.1% Increase FIT gfobt Southern Mid & NW 7.3% 7.0% 290,000 Additional screens each year! 50% 55% 60% 65% 70%

38 % Positivity & Screening Episode 0.0% 2.0% 4.0% 6.0% 8.0% 10.0% 12.0% 14.0% Both Southern Mid & NW FIT Cut-off - 20 ug Hb/g Faeces Prevalent Episode Southern Mid & NW Southern Mid & NW 0.0% 2.0% 4.0% 6.0% 8.0% 10.0% 12.0% 14.0% Both Incident Episode 0.0% 2.0% 4.0% 6.0% 8.0% 10.0% 12.0% 14.0% Both First Screening Episode

39 Outcome Mean FIT Conc. ug Hb /g faeces Positives at 20 ug /g Cut-off Normal 10 (1-20) 6.9% All adenoma 14 (4-23) 9.3% Adv. adenoma 81 (37-125) 34.5% Cancer 170 (89-252) 84.6% Endoscopic Classification Histology Mean FIT Conc. ug Hb /g faeces +ve at 20 ug /g Cut-off LGD % HGD % Size < 10 mm % 10 mm % Number < 3 adenoma % 3 adenoma %

40 Age-Specific Incidence Rates /100,000 Population Annual Colorectal Cancer Rates UK Male Rates Female Rates Higher Risk of Harm Benefit? Harm? Lower Risk of CRC Age range for screening 40 to to to to to to to to to to 89 Age Range

41 Cancer Detection Rate 0.45% Age & FIT Threshold Cancer Detection Rate 0.40% 0.35% 0.30% 0.25% % 0.15% 0.10% 0.05% 0.00% FIT 20 FIT 100 FIT 150 FIT180 gfobt Age Group

42 FIRST PREVALENT INCIDENT FIRST PREVALENT INCIDENT FIRST PREVALENT INCIDENT FIRST PREVALENT INCIDENT FIRST PREVALENT INCIDENT FIRST PREVALENT INCIDENT FIRST PREVALENT INCIDENT FIRST PREVALENT INCIDENT FIRST PREVALENT INCIDENT FIRST PREVALENT INCIDENT FIRST PREVALENT INCIDENT % Cancer Detection Rate Screen Episode & FIT threshold Cancer Detection Rate 0.6% First Invitation (60 year olds) No response to previous invitations Participated previously 0.5% 0.4% 0.3% 0.2% 0.1% 0.0% FIT gfobt 140 gfobt

43 1 st Invitation 2 nd Invitation 3 rd Invitation Very Poor Adherence Poor Adherence Full Adherence Colorectal cancer screening uptake over three biennial invitation rounds in the English bowel cancer screening programme. Lo SH, et al. Gut 2014 Adherence to screening % Uptake over 3 episodes Risk associated with screening history Include in FIT algorithm 1. Period since last screen? 2. Previous screening outcomes 3. Surveillance details % 1 in 3 61% 2 in 3 44% 3 in 3 In hot countries 1. Ambient temperature 2. Travel time to laboratory All held on screening database! 1st Episode 2nd Episode 3rd Episode At least once At least twice At least 3 times

44 Retrospective study 2.5 million UK people Full blood count data on GP records. The algorithm offers an additional means of identifying risk of colorectal cancer, and could support other approaches to early detection, including screening

45 70% Ulcerative colitis Crohn's colitis 22-33% Type II diabetes 33% Gallstones 33-41% 25% Family history of colon cancer Metabolic syndrome Personal cancer history - (colon, rectum, ovary, endometrium, or breast)

46 21% 12% 12% 8%

47 Future of Quantitative FIT FIT-based Multivariate Risk Assessment Quantitative FIT concentrations & trends (ambient temp /elapse time?) Multivariate Bowel Cancer Risk Score Age & Sex Screening history Indices of Deprivation Postcode Medical History IBD, Crohns, DM, etc Stage 1-2 Assess - risk at onfit receipt invitation of FIT Referral to colonoscopy with If low improved risk PPV & cost delay effectiveness invitation Family History 1 st and 2 nd deg. relatives Life style Smoking, exercise, diet, obesity

48 Collaborators Jennifer Cooper, Nick Parsons, Sian Taylor-Phillips Multivariable Risk Prediction Model Logistic linear regression Artificial neural networks Machine learning Neural networks in the lead Jennifer Cooper Neural Network Feed forward neural network, 18 weights. Weight decay 0.01 Risk-adjusted colorectal cancer screening using the FIT and routine screening data: development of a risk prediction model Jennifer Cooper et al British Journal of Cancer (2017), 1 9 doi: / bjc

49 FIT An opportunity to personalise population-based screening? Better Screening by - focusing on individuals...as well as on populations? Personalising Population-based Screening 1. Intelligent use of FIT data 2. Incorporate personal risk 3. Personalised interpretation of the FIT Screen