The Dutch bowel cancer screening program Relevant lessions for Ontario

Transcription

1 The Dutch bowel cancer screening program Relevant lessions for Ontario Ernst J Kuipers Erasmus MC University Medical Center Rotterdam - The Netherlands 1

2 Ismar Boas ( )

3 Colorectal cancer screening is rapidly expanding Schreuders E et al. Gut 2015

4 Annual number of German men undergoing colonoscopy screening Brenner H et al. Gastroenterology 2015

5 Asia-Pacific Working-Group on CRC Screening Guidelines Sung JJ, et al. Gut 2014 Hong Kong, June 9-10, 2013

6 Map of Ontario versus Netherlands 17 million 6

7 Density of Netherlands compared to North American cities The Netherlands is not a densely populated country, but rather a thinly populated city Nederland 17 miljoen

8 Picture of dog 8

9 Bowel cancer screening in NL; stakeholder positions in 2005 Ministry of Health: Reluctant Impact of breast and cervical cancer screening uncertain This also pertained to other national programs, such as ongoing campaign to reduce smoking Uncertainties on optimal bowel cancer screening strategy Worries about capacity issues and costs

10 Pictures of colorectal cancer screening process 10

11 More pictures of colorectal cancer screening program 11 11

12 Bowel cancer screening in NL; stakeholder positions in 2005 Ministry of Health: Reluctant General population: Unaware 12

13 Bowel cancer screening in NL; stakeholder positions in 2005 Ministry of Health: Reluctant General population: Unaware Health insurers: Not interested 10-20% of population annually switch insurer Long-term benefit of screening for population of one insurer thus unclear 13

14 Bowel cancer screening in NL; stakeholder positions in 2005 Ministry of Health: Reluctant General population: Unaware Health insurers: Not interested Physician organizations: Opposed >90% of endoscopies performed by gastroenterologists Shortage of staff, waiting lists 14

15 Effect of rising chemotherapy cost on the cost savings of colorectal cancer screening Screening costs and treatment savings per individual US$ HemII FIT FSig Cscopy Lansdorp-Vogelaar I et al. JNCI

16 Recommendation National Health Council and Dutch Cancer Association 2005 Seriously consider introduction of a national CRC screening program...but first provide insight into the following issues; optimal screening-strategy population participation program organization role primary care physician quality assessment program

17 17 Celebration picture

18 The impact of colorectal cancer screening The impact of screening on CRC incidence and mortality rests on: the (repeated) uptake of the test the ability to detect CRC at all stages and locations the ability to detect advanced adenomas at all locations Kuipers EJ et al. Nat Rev Clin Oncol 2013

19 The impact of colorectal cancer screening The impact of screening on CRC incidence and mortality rests on: the (repeated) uptake of the test the ability to detect CRC at all stages and locations the ability to detect advanced adenomas at all locations Impact defined by: Accuracy of screening test Proportion of the population covered / screening status up to date Kuipers EJ et al. Nat Rev Clin Oncol 2013

20 The impact of colorectal cancer screening The impact of screening on CRC incidence and mortality rests on: the (repeated) uptake of the test the ability to detect CRC at all stages and locations the ability to detect advanced adenomas at all locations Impact defined by: CRC incidence and mortality population trends over time CRC incidence and mortality among screened vs non-screened Kuipers EJ et al. Nat Rev Clin Oncol 2013

21 The incidence of colorectal cancer in Italian regions related to their timing of introduction of CRC screening Zorzi M et al. Gut 2015; 64:784-90

22 The impact of colorectal cancer screening The impact of screening on CRC incidence and mortality rests on: the (repeated) uptake of the test the ability to detect CRC at all stages and locations the ability to detect advanced adenomas at all locations Impact defined by: Screening Uptake (%) x Positivity Rate (%) x Pos Predictive Value (%) = Number of screenees diagnosed with advanced neoplasia per 1000 invited Kuipers EJ et al. Nat Rev Clin Oncol 2013

23 The Dutch pilot; a close combination of randomized studies and simulation modeling Randomized trials in screening-naive population with follow-up Pre-randomized designs (i.e. first randomization, then approach for consent and participation) Comparison between different screening methods and screening intervals Use of low cut-offs for colonoscopy referral

24 CRC screening in average risk screening-naïve individuals aged years in Rotterdam area % Adherence % positive test % true positives* True positives per 1000 invited gfobt FIT Sigmoidoscopy Hol L et al. Gut 2010

25 CRC screening in average risk screening-naïve individuals aged years in Rotterdam area % Adherence % positive test % true positives* True positives per 1000 invited gfobt FIT Sigmoidoscopy Sigmo + FIT Kuipers EJ et al. Nat Rev Clin Oncol 2013, Hol et al. Gut 2010, Hol et al. Int J Cancer 2011

26 van Dam L et al. Lancet Oncol 2012 The price of autonomy; should screenees be offered a choice?

27 The Dutch pilot; a close combination of randomized studies and simulation modeling MISCAN microsimulation modeling to assess screening scenarios in terms of: Screening age-range (age to start and stop screening) Screening interval Cut-off of screening test Number of tests per screening round

28 Screening strategies; opportunities to tailor based on local needs and resources FIT screening strategies: Targeted age-range Test cut-off Screening interval Number of tests per screening round

29 MISCAN-Colon model for CRC screening ADENOMA Preclinical CANCER Clinical CANCER No lesion adenoma <=5 mm adenoma 6-9 mm preclinical stage I preclinical stage II preclinical stage III clinical stage I clinical stage II clinical stage III death colorectal cancer adenoma >=10 mm preclinical stage IV clinical stage IV Data sources: Adenoma Autopsy studies Endoscopy studies Preclinical Cancer gfobt trials Clinical Cancer Cancer registries Death Cancer registries National Statistics Buro

30 Cost performance modelling of gfobt and FIT Van Wilschut JA, van Ballegooijen M, et al. Gastroenterology 2011

31 CRC screening in average risk screening-naïve individuals aged years in Rotterdam area % Adherence % positive test % true positives* True positives per 1000 invited gfobt FIT Sigmoidoscopy CTC Colonoscopy Kuipers EJ et al. Nat Rev Clin Oncol 2013, Hol et al. Gut 2010, Stoop et al. Lancet Oncol 2011

32 Diagnostic yield of colonoscopy Prevalence of advanced neoplasia Primary screening colonoscopy: 5 10% Symptomatic patients: 10 15% Secondary secondary screening colonoscopy in FIT-positives: 30 60%

33 Comparison of CRC screening in average risk screeningnaïve individuals aged years in Rotterdam area % Adherence % positive test % true positives* True positives per 1000 invited gfobt FIT Sigmoidoscopy CTC Colonoscopy round FIT round FIT Hol et al. Gut 2010, Stoop et al. Lancet Oncol 2011, Kapidzic et al. AJG 2014, Grobbee et al. In preparation

34 Two-round FIT50 screening with 1-, 2-, or 3-year interval; advanced neoplasia detection rates Detection rate of advanced neoplasia % N = 6111; Van Roon A, et al. Gut 2012

35 Four biennial rounds of one- versus two-sample FIT screening; positivity rate * 29 1-FIT 2-FIT 25 * P< * 12.7 * * * Round 1 Round 2 Round 3 Round 4 Cumulative Schreuders E et al. Submitted

36 Four biennial rounds of one- versus two-sample FIT screening; detection rate Detection rate advanced neoplasia PPV advanced neoplasia 5 4 % % 50 1-FIT 2-FIT Round 1 Round 2 Round 3 Round 4 Round 1 Round 2 Round 3 Round 4 Schreuders E et al. Submitted

37 True positives with advanced neoplasia per 1000 invited Round Cumulative 1 2 Cumulativ Colonoscopies 3 4 needed e 1-FIT FIT Schreuders E et al. Submitted

38 Cost-effectiveness of one versus two sample FIT testing Life years gained sFIT 2sFIT(both pos) 2sFIT(mean pos) 2sFIT( 1 pos) Eff. Frontier Costs (x1000 euro's) Van Roon AH et al. CGH 2011, Goede L et al. Gut 2013

39 Uptake of colonoscopy among FIT-positives in the Rotterdam pilot 92 96%

40 Randomized trial to assess impact of advance notification on uptake of FIT screening Advance notification increased adherence from 61.1 to 64.4% Costs per additional detected advanced neoplasia 957 euro Van Roon AH et al. Prev Med 2011

41 P a rtic ip a tio n (% ) Participation per screening round in the pilot re s p o n s e a fte r re m in d e r re s p o n s e in itia l in v ite S c re e n in g ro u n d Van de Vlugt M et al. Br J Cancer 2017

42 Gradual invitation of subsequent birth cohorts

43 FIT tender FOB-Gold (Sentinel, Italy) won public tender over OC-Sensor (Eiken, Japan) A cut-off for referral to colonoscopy of 15µg/g was chosen

44 Mailing

45 Protocol for the authorization and auditing of colonoscopy centres and endoscopists

46 Colorectal cancer screening in NL Kuipers EJ et al. Nat Rev Clin Oncol 2013

47 FIT positivity and detection rates in the Netherlands Pilots cut-off 10 µg Hb/g National program 1st phase cut-off 15 µg Hb/g Participation (%) FIT positivity (%) Detection of CRC* Detection of AN* PPV for CRC (%) PPV for AN (%) NN Scope for AN *N per 1000 screened Penning C et al. In preparation; results of first invited

48 Waiting list in 2014 for colonoscopy after positive FIT 100% 90% 80% 70% 60% 50% 40% 30% 20% 6 wk 5 wk 4 wk 3 wk 2 wk 10% 0%

49 Consequences for the Expected Colonoscopy Demand

50 Reduction in number of invitations

51 Positivity rate (%) Problem analysis: comparison between national programme and pilot studies positivity rate Programme Pilot Grobbee EJ et al. Gut 2017

52 Detection rate (%) Problem analysis: comparison between national programme and pilot studies detection rate Programme Pilot Grobbee EJ et al. Gut 2017

53 Detection rate (%) Problem analysis: comparison between national programme and pilot positivity vs detection rate Pilot Positivity rate (%) Programme Grobbee EJ et al. Gut 2017

54 Options to meet colonoscopy demand Increase colonoscopy capacity Reduce colonoscopy demand Slow down rate of invitations Change implementation scheme Increase cut-off value Increase screening interval

55 Model-based calculations for the most optimal reduction in colonoscopy demand Toes-Zoutendijk E et al. Gastroenterol 2017

56 FIT positivity and detection rates in the Netherlands Pilots cut-off 10 µg Hb/g National program 1st phase cut-off 15 µg Hb/g National program 2nd phase cut-off 47 µg Hb/g Participation (%) FIT positivity (%) Detection of CRC* Detection of AN* PPV for CRC (%) PPV for AN (%) NN Scope for AN *N per 1000 screened Toes-Zoutendijk E et al. Gastroenterol 2017

57 The best laid plans: Adaption is an essential part of going from efficacy research to program implementation Levin T. Gastroenterol 2017

58 Longer-term implications of the national programme: colonoscopy demand

59 Waiting list in 2014 for colonoscopy after positive FIT 100% 90% 80% 70% 60% 50% 40% 30% 20% 6 wk 5 wk 4 wk 3 wk 2 wk 10% 0% 59

60 Number of CRCs diagnosed in 2013 and 2014, listed per year of birth Screening started in 2014; first approaching subjects born in 1938, 39, 47, 49, and 51 CRC incidence increased 12% from (2013) to (2014) Toes-Zoutendijk et al; results of first invited

61 Results of million persons invited 1.0 million participants positive test results persons underwent colonoscopy: colorectal cancers advanced adenomas

62 Participation rate 2016 First round Second round 71.8% 75.9%

63 Positivity rate 2016 First round Second round 6.1% 4.5% Cut-off level 47 µg Hb/g

64 Yield of colonoscopy First round Second round 20% 8% 7% Colorectal cancer 25% Advanced adenoma 5% 6% 35% Non-advanced adenoma 45% Serrated polyps 22% 27% No polyps or tumours

65 Positive predictive value First round Second round CRC 8.3% 6.6% CRC + AA 53.7% 42.1% Toes-Zoutendijk E et al. Submitted

66 Detection rate First round Second round CRC CRC + AA

67 Stage distribution of colorectal cancer Screen-detected CRCs have a more favourable stage distribution percentage (%) (stage I and II) than symptom-detected CRCs (67% versus 40%) I II III IV screen-detected I II III IV percentage (%) I II III IV symptom-detected I II III IV

68 Uptake of colonoscopy among FIT-positives in the national program 82.8% (- 89%)

69 Complications in colonoscopies

70 Interval cancers in subjects undergoing multiple rounds of FIT screening 27 / 157= 17% FIT cancer miss rate Van de Vlugt M et al. Gastroenterol 2017

71 Interval cancers in subjects undergoing multiple rounds of FIT screening Van de Vlugt M et al. Gastroenterol 2017

72 0 / 0 Number of cancers = Interval cancers in FOBT-based colorectal cancer population screening programme: implications for stage, gender and tumour site 1 st round: nd round: rd round: 389 Steele RJC, et al. Gut 2012 Target population 317,000, 3 biennial rounds of gfobt screening

73 Interval cancers in subjects undergoing colonoscopy screening patients diagnosed with CRC and having had a screening colonoscopy, (91%) were diagnosed at the screening colonoscopy (9%) were diagnosed within 3 years after the screening colonoscopy Baxter NN et al. Gastroenterol 2011

74 Risk of advanced neoplasia depends on baseline FIT, even at low levels in the negative range 40 0 µg Hb/g 0-2 µg Hb/g cum. incidence of AN (%) p<0.001 >2-4 µg Hb/g >4-6 µg Hb/g >6-8 µg Hb/g >8<10 µg Hb/g years Subjects at risk > Subjects at risk > Subjects at risk > Subjects at risk > Subjects at risk >8-< Subjects at risk

75 Potential relevant lessons for Ontario Focus on one dominant screening strategy and lower threshold to participate as much as possible If FIT-based: Mail kits to home address Consider pre-invitation letter Mail reminder with 2 nd kit in case of non-response Make mailings stand out and use image of mailing in all communications With respect to colonoscopy: Target limited capacity towards optimal impact Risk of AN FIT-positives > symptomatic patients > healthy subjects! Quality assurance and accreditation, for instance linked to reimbursement

76 Conclusions Nearly all European countries are implementing CRC screening They use different approaches Primary colonoscopy screening tends to be associated with low participation, and thus little impact on CRC incidence and mortality Guaiac-FOBT based programs are being replaced by FIT programs FIT programs have the highest population participation Modeling can help to devise the most optimal program for a particular country or region for optimal use of available resources, participation, 76

77 Picture of beach 77