Prof Stephen P. Halloran. Update on the NHS Bowel Cancer Screening Programme Focus on BS & FIT

Transcription

1 Prof Stephen P. Halloran Update on the NHS Bowel Cancer Screening Programme Focus on BS & FIT

2 World Top 20 Cancers Men Incidence & Mortality (2012) Women World Colorectal 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

3 W. Europe Top 20 Cancers Men Incidence & Mortality (2012) Women World Colorectal 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

4 Bowel Cancer Regional analysis Men Incidence & Mortality (2012) Women Incidence Mortality Price we pay for affluent lifestyle Pay a price for cancer treatment GLOBOCAN 2012 (IARC) Estimated age-standardised rates/100,000

5 Colorectal cancer mortality in Europe. Men & Women and 2011 RESEARCH Trends in colorectal cancer mortality in Europe: retrospective analysis of the WHO mortality database Ouakrim DA, Autier P et al BMJ 2015;351:h4970 Colorectal cancer deaths per people Colorectal cancer deaths per people Colorectal cancer deaths per people Colorectal cancer deaths per people Colorectal cancer deaths per people Colorectal cancer deaths per people Austria 60 Men 50Mortality Bulgaria Denmark France Hungary Italy Falling Women Year Belarus Mortality Rising Croatia Estonia Germany Iceland Latvia Year Belgium Czech Republic Finland Greece Austria Lithuania 2020 Year Colorectal cancer deaths per people Colorectal cancer deaths per people Colorectal cancer deaths per people Colorectal cancer deaths per people Colorectal cancer deaths per people Colorectal cancer deaths per people Luxembourg Netherlands Portugal Slovakia Sweden United Kingdom Men Women Year TFYR Macedonia Norway Romania Slovenia Switzerland EU-27 Year Malta Poland Russian Federation Spain Ukraine United States 2020 Year

6 Predicted increase in the incidence of colorectal cancers in EU countries from 2012 to 2025 (Population forecasts were extracted from the United Nations, World Population prospects, the 2012 revision)

7 Colorectal Cancer Pathogenesis Case for Screening Cancer Stage Screening Colonoscopy 30 to 45 mins 1 Look for cancers 2 remove by 3surgery 4 Look for polyps remove by polypectomy 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

8 Screening is the process of identifying healthy people who may be at increased risk of disease

9 Haem 2H 2 O 2 = 2H O 2 Guaiac FOBt Oxidised guaiaconic acid is blue

10 20-25 years ago Four Large Randomised Controlled Trials gfobt Bowel Cancer Screening Overall 16% reduction in mortality Minnesota Nottingham Funen France Amongst those who did the tests 23% reduction in mortality

11 SC SC Bowel Cancer Screening England - July 2006 SC SC SC SC Southern Hub (Guildford) SC SC SC Colonoscopy Site Screening Centres (18) Colonoscopy Site Clinic Sites Clinic Sites Clinic Sites SC SC SC SC SC SC SC 14.6 million

12 Screening Timeline Start 2 yearly Screening Cycle Day 8 Day 1 Invitation Kit & Spatula Return Envelope <2 days +ve Result Patient & GP Letter Kit Read (1 day) SSP Clinic Appointment <14 days <14 days 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 (

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14 Five-Year Net Survival by Age England

15 Once in a lifetime flexisigmoidoscopy England July 2006 Phase year olds Phase Phase 3 <60 15

16 Once in a lifetime flexisigmoidoscopy 1.2 Cumulative incidence distal cancer (%) Control Screened Not Screened Atkin et al. Lancet. 2010;375: Outcome - Invited (participated) Incidence reduction 23% (33%) Mortality reduction 31% (43%) Time from randomisation (years)

17 Bowel cancer screening Flexible sigmoidoscopy RCTs 1. Atkin WS et al. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet 2010;375(9726): Segnan N et al. Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian Randomized Controlled Trial SCORE. J Natl Cancer Inst 2011;103(17): Epub 2011/08/ Schoen RE et al. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. New England Journal of Medicine 2012;366(25): (PLCO Trial) 4. Holme Ø et al. Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial. JAMA 2014;312(6): Reduction in UK Italy US Norway Incidence 23% 18% 21% 20% Mortality 31% 22% 26% 27%

18 44% attendance (7,439 have colonoscopy) About 53% response Works in Northern Italy? Invite to FS when 58 years old 19% uptake of FS Invited to do FIT after 6 months 23% uptake of FIT Re-invited twice to do FS - if not then FIT Overall 2 years 40 42% (FS and FIT) Relevant Pathology

19 %Uptake in Taunton & Bristol 2013/4

20 %Uptake in Bristol 2013/4

21 FOBT kit return First 2.6 million invitations in England 80 Percentage of test kits returned Gender Age Area ethnic diversity Area deprivation von Wagner C, Baio G, Raine R et al. (2011) Int J Epidemiol 40,

22 % Uptake - 3 Episodes (E1, E2 & E3) Adherence Adherence to screening? % 1 in 3 61% 2 in 3 Southern Hub Data 44% 3 in st Invitation 2 nd Invitation 3 rd Invitation Very Poor Adherence Poor Adherence Full Adherence 1st Episode 2nd Episode 3rd Episode At least once At least twice At least 3 times

23 NIHR Programme Grant for Applied Research The ASCEND study: Strategies to reduce the social gradient in bowel cancer screening uptake

24 Very 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, Halloran S, 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, Halloran S, et al. LANCET 387(10020): Colorectal cancer screening uptake over three biennial invitation rounds in the English bowel cancer screening programme Lo SH, Halloran S et al. 2nd Digestive-Disorders-Fed. Conf., London,, GUT. BMJ. 64: A373-A

25 Blood in faeces still the best marker for population-based screening!

26 Faecal Immunochemical Test (FIT) gfobt Globin (Human) Haem Guaiac test gfobt

27 FIT measure of Faecal Haemoglobin Concentration FIT Concentration relates to disease severity Outcome Mean FIT Conc. ug Hb /g faeces Positives at 20 ug /g Cut-off Endoscopic Classification Mean FIT Conc. ug Hb /g faeces +ve 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% Histology LGD % HGD % Size < 10 mm % Cancer 170 (89-252) OC-SENSA MICRO 84.6% 10 mm % Number < 3 adenoma % 3 adenoma %

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

29 Uptake & Deprivation (IMD Index of Multiple Deprivation) 2014 Pilot 75% gfobt 70% 65% 6.7% 6.0% 6.8% FIT 60% 8.0% 55% 50% 7.9% 45% 40% IMD 1 (Posh) IMD 2 IMD 3 IMD 4 IMD 5 (Poor)

30 Uptake at First Invitation 2014/5 South, Midlands, NW & London Pilots Both 1 st invitation (mostly 60 year old subjects) FIT gfobt 10.9% Increase Southern 9.7% 38.6% London 52.4% 14.4% Increase Mid & NW 12.2% 40% 45% 50% 55% 60% 65%

31 Uptake in Prevalent Episodes 2014/5 South, Midlands, NW & London Pilots Both 1 5 invitations but no previous response FIT gfobt 11.6% Increase Southern Mid & NW London 9.7% 11.3% 11.8% 19.5% 9.8% Increase 0% 5% 10% 15% 20% 25% 30%

32 Uptake in Incident Episodes 2014/5 South, Midlands, NW & London Pilots Both 1 5 previous participation episodes 4.2% Increase FIT gfobt Southern 4.1% Mid & NW 4.3% 82% 84% 86% 88% 90% 92%

33 Uptake & All Episodes 2014 South, 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%

34 Colonoscopy gfobt FIT 180 FIT 150 FIT 100 FIT 40 FIT 20 Cancer Normal 17.5% 8.3% 4.0% 10.1% High-risk Adenoma 14.0% Intermediate-risk Adenoma 30.6% Abnormal 19.5% Low-risk Adenoma

35 Colonoscopy gfobt Normal Cancer FIT % 10.6% High-risk Adenoma Polypectomy rate increase >64% with 16.5% 23.9% more polyps in each category Intermediate-risk Adenoma Abnormal 18.6% 18.3% Low-risk Adenoma

36 % Positivity & Deprivation FIT Cut-off - 20 ug Hb/g Faeces 12.0% 10.0% 8.0% 6.0% 4.0% 2.0% 0.0% IMD 1 (Posh) IMD 2 IMD 3 IMD 4 IMD 5 (Poor)

37 FIT ThresholdandPositivity (BCSP in England) 9.0% 8.0% 7.9% 7.0% 6.0% 5.0% 4.0% 3.0% 2.0% 1.0% 1.7% 1.56% 0.0% gfobt FIT 20 FIT 40 FIT 100 FIT 150 FIT 180 ug Haemoglobin / g Faeces

38 Faecal Immunochemical Test (FIT) & Positivity Thresholds adopted by National Bowel Cancer Screening Programmes (1 st October 2016) Predicted FIT positivity - % of participants referred for colonoscopy 12% 7.8% 5.2% 2.9% 2.1% 1.7% 1.5% England (April 2018) Scotland (Dec. 2017) Netherlands Southern Ireland New Zealand Canada (Quebec) France Portugal Norway (pilot) Denmark Hungary Iceland (planned) Italy (North <20) Korea Malta Singapore Slovenia Spain (Catalonia)<20 Taiwan Uraguay England (pilot) Australia Lithuania (pilot) Latvia (pilot) Belgium (Flanders) Switzerland (no t Netherlands (pilot) New Zealand (pilot) Israel Austria Sweden (pilot) Colonoscopy Capacity Problems Threshold used in the FIT pilot in England? Faecal Immunochemical Test (FIT) threshold (ug haemoglobin /g faeces)

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

40 Screen Episode & FIT threshold Cancer Detection Rate 0.6% First Invitation (60 year olds) No response to previous invitations Participated previously % Cancer Detection Rate 0.5% 0.4% 0.3% 0.2% x5.1 x % x1 0.0% FIT 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 gfobt 140 gfobt

41 0.45% Age & FIT Threshold Cancer Detection Rate 0.40% 0.35% Cancer Detection Rate 0.30% 0.25% 0.20% 0.15% 0.10% 0.05% 0.00% FIT 20 FIT 100 FIT 150 FIT180 gfobt Age Group

42 Sex & FIT threshold % Positivity 90% 10.0% % Missed neoplasms relative to those detected using 20ug/g cut-off 80% 70% 60% 50% 40% 30% 20% 10% % FIT Positivity 9.0% 8.0% 7.0% 6.0% 5.0% 4.0% 3.0% 2.0% 1.0% Positivity Why a gender difference? More disease FIT more sensitive 0% 0.0% FIT (OC-Sensor) Cut-off (ug/g)

43 The Power of Quantitative FIT Multivariate Risk Scores Quantitative FIT concentration Age & Sex Screening history Multivariate Bowel Cancer Risk Score Better Personalised Population-based Screening! Positive Predictive Values Cost Effectiveness Colonoscopy Referrals Indices of Deprivation Geodemographics (Postcode) Medical History IBD, Crohns, DM, etc Family History 1 st and 2 nd degree relatives Life style Smoking, exercise, diet, obesity

44 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 (variable cut-offs) 2. Incorporate personal risk in a Multivariate Risk Scores 3. Personalised invitation which is sensitive to sex & screening history

45 FIT 4 Me Screening Systems