Improving Outcomes in Colorectal Cancer Screening

1. Improving Outcomes in Colorectal Cancer Screening Graeme P Young Flinders Centre for Cancer Prevention and Control. Flinders University

2. Outline • Screening concept • Evidence overview for screening • Improving outcomes: Crucial points where screening can be improved • Screening pathway • Improvements that are feasible • Behavioural • Technological • Quality

3. What is screening? • Screening is the testing for presence of disease in apparently healthy people, where they have no recognised increase in risk for that disease. • Key goal: To reduce the community burden of “dis-ease” • Measured as a reduction in mortality from CRC. • Bonus benefit: a reduction in incidence as well if we detect preinvasive lesions (adenomas)

4. Window for detecting curable disease Development is initiated Curable disease Point of usual medical care. Healthy Well-being Death Age

5. Screening pathway Engage subject Negative Screening test Positive Colonoscopy Treatment Follow-up/Surveillance

6. CRC Screening - Evidence for GFOBT Two-step screening using a faecal occult blood test (FOBT) has been shown to be effective in population RCTs; i.e. no bias. All have used a guaiac-FOBT (GFOBT, Hemoccult). • 4 of 5 RCTs found a reduction in mortality • ↓15-35% on intention-to-screen analysis • ↓ >40% in those who did the test • The longest study reported (18y; Minnesota) found a reduction in incidence • ↓20% on intention-to-screen analysis

7. CRC Screening – evidence for colonoscopy • One-step screening by colonoscopy or by sigmoidoscopy is supported by case-control studies only. • There have been no true population RCTs • Case-control studies over-estimate benefit • While colonoscopic screening will have impact on incidence and mortality, the benefit relative to FOBT screening remains uncertain.

8. Improving outcomes - Crucial points • Mortality & incidence reductions achieved with FOBT RCTs are modest, so how do we improve effectiveness? • Mortality reduction depends on invitees re-testing at least second-yearly over ten years. • Strategies: • Ensure all elements of the pathway are in place • Improve screening participation rate • Improve sensitivity for cancer and adenomas • (Remove restrictions due to inflexible test endpoint) • (Ensure wide-spread access) • Ensure high quality at all stages

9. Screening pathway Subject must do the screening test Engage subject Negative Screening test Positive Colonoscopy Treatment Follow-up/Surveillance

10. Why improve participation? • Without participation there is no detection! • Intention-to-screen outcomes are not as good as outcomes based on participation • Effectiveness requires RE-participation • Detection in a population is not only related to technological advances Detection = sensitivity X participation

11. Population Behaviour Studies, Flinders • Factors that influence initial participation in screening • 1997 Impact of diet restriction • 1998 Influence of General Practice endorsement. • 2000 Impact of new test technologies. • Community attitudes to screening and strategies for improvement. • 2006 One versus two faecal specimens • 2005 Improved communication strategies. • Factors that influence re-participation in screening 1998 – 2005 Repeat offers of screening to all who were offered first round.

12. Novel stool sampling with FIT Guaiac-FOBT Faecal immunochemical test - FIT InSure Hemoccult, Hemoccult ICT

13. Population Participation Study Goal: Compare GFOBT with FIT Subjects: General popn in Adelaide, age 50-70. Random selection from electoral roll Screening kits were mailed out from the Bowel Health Service. A different test kit was sent to three separate cohorts: Hemoccult II (GFOBT, stick sampling, diet restricted), Hemoccult ICT (FIT, stick, no diet) InSure (FIT, brush-sampling, no diet) Cole et al J Med Screening, 2003; 10: 117-122

14. Easy sampling improves participation 67% InSure Hemoccult ICT • Cole et al J Med Screening, 2003; 10: 117-122

15. What is the value of raising awareness? • 2400 people (age >50) selected to receive an invitation and FIT kit. Randomisation (n=600): • Standard Invitation Letter • Additional messages of risk expressed in terms of generalised risk, positive framing and relative risk. • Lay advocacy that highlighted the value of screening, ease of testing, and importance of screening + kit. • Standard invitation letter as in Group 1 plus an information letter two weeks prior. • Designed to advance people along the stages-of-change model so that they bare informed and prepared to receive an offer of a kit

16. Advance information benefit P < 0.05 12%

17. Pathway – improving detection Engage subject Negative Screening test Positive Colonoscopy Simple tests select out those who proceed to colonoscopy Treatment Follow-up/Surveillance

18. FOBT refines likelihood for cancer

19. Improving detection • Improve accuracy of FOBT • Improve accuracy of colonoscopy

20. Improving faecal blood tests Haemoglobin Haem Globin Guaiac; peroxidase. Interference by Meat, vegies, vitamin C, NSAIDs. Detects bleeding from Stomach, small & large intestine. Immunochemical. NO Interference. Detects bleeding from large intestine. GFOBT FIT Faeces

21. Paired comparison of GFOBT and FIT • AIM: Ascertain relative detection rate and false-positive rates of a brush-sampling FIT (InSure) compared to a stick sampling sensitive GFOBT (Hemoccult Sensa). • DESIGN: All subjects completed both tests (qualitative), prior to colonoscopy • COHORTS: Diagnostic (n=400) and screening (n=3500) • Smith et al Cancer. 2006;107:2152-2159

22. FIT Identify more Cancers Early Stage cancers – n=24 Difference 33%, CI 11-55% Smith et al Cancer. 2006;107:2152-2159

23. InSure vs HOSensa; adenomas Screen-detected significant adenomas – n=45 Difference 20%, CI 5.4% to 34.6% Smith et al Cancer. 2006;107:2152-2159

24. RCT – GFOBT vs FIT • Van Rossum et al. Gastroenterol 2008;135:82-90 • Population RCT comparing GFOBT (hemoccult) with FIT (OC-Sensor) in 20,623 individuals.

25. FIT can be quantitative Test InSure test; Enterix Inc Control

26. Faecal [Hb] relates to diagnosis Median, IQR

27. Detection versus positivity rate Neoplasia Detection rate Test Positivity Rate N=4,100 approx

28. FIT are much better than GFOBT Make it easier for screenee Remove need for diet and drug restriction Easier stool-sampling methods Improved sensitivity/specificity balance More sensitive (including adenomas) but specificity is controlled Selectively target colonic bleeding Avoid diet and drug interference Improve discrimination and control quality Easier-to-read endpoint Faecal analyte is more precise Allow quantification Allow automation GFOBT FIT

29. Screening pathway Engage subject Negative Screening test Colonoscopy and treatment must be of high quality Positive Colonoscopy Treatment Follow-up/Surveillance

30. Straight to colonoscopy – or not? Target high-risk Colonoscope Everyone! Proportion of Population aged >50 years

31. Keys to quality with colonoscopy • Good training • Ongoing training • Objective measurement of quality indicators • Computerised reporting and data collection • Audit and peer-review • Adequacy of polypectomy • Be prepared to act when poor quality is identified. • Monitor adverse events

32. Reporting of findings - Australia

33. What standards are expected • Adenoma detection rate • Relative to peers in similar environment • Retrieval rates for pathology when polyp is removed (site in colon identifiable) • Caecal intubation rate • >90%, probably >95% • Withdrawal time • 6 or more minutes • Re-examination rates (poor bowel preparation, too many polyps)

34. Colonoscopy vs Mountain Climbing

35. Conclusions • Screening is for well people; “do no harm”. • Screening is a repeated program with several steps, not just a single test. • Participation is crucial • Without participation there is no benefit • Test accuracy can be improved. • FIT improve adenoma detection rates • FIT also provide flexibility. • Quality of colonoscopy is crucial. • The view is more important than the conquest

36. We can delay your demise! or prevention.

38. Achieving quality in a pathway Drivers of quality • Understand what we intend to do • Pick a fully committed team • Do it • Monitor what is being done • Revise according to efficacy, effectiveness, plus unexpected risks, problems and barriers. Detail follows rather than leads

39. The key measures (provisional) • Participation rate - acceptance • Test positivity rate - cost • Referral rate for colonoscopy – risk management • Downstaging – impact on mortality • Adenoma detection rate – impact on incidence • Colonoscopy quality measures • Program • Repeat participation rate • Incremental CPLYS, DALYs • Participant satisfaction • Follow-up of high risk groups • Workload impact • Later • Interval cancers

41. Refining the risk Target high-risk Colonoscope Everyone!

42. WHO requirements of a screening test Given that CRC is an important problem, has a suitable natural history, is accurately diagnosable and effectively treated in the early stages (Watson and Junger WHO Public health Paper no 34, 1968): The test should: • Be shown in the absence of bias to reduce mortality (and incidence) • Be cost-effective • Be acceptable to the people being targeted The program: • Be feasible within the health care system • Diagnosable, follow-up testing, reparticipation in screening • Benefit outweighs the down-side

43. 2. Contexts and dimensions • Health care system • Who organises screening • Is there a public health process • Who funds screening • Simple reimbursement • Program elements • Entire program

44. Issue 8 - Overall program evaluation • Is there a public health benefit? • Set objectives related to steps in the program • Relative to a relevant baseline • Relative to an expectation (no baseline) • Collect data that pertains to those objectives • Value of surrogate endpoints • Give quick indication of impact

45. Screening pathway Engage subject neg. High risk Aver. risk Screening test pos. Colonoscopy Treatment Follow-up/Surveillance

46. Australia - Register and Data collection • Track participants through pathway • Offers FIT, provides reminder • Monitors results • Make payments to clinicians for information on events • Limited success in pilot • Ascertain cancers through state cancer registers • Endpoints - minimum data set • 25 outcomes address success, failure and quality • Not available in real time to pathway coordinators • Inadequate for research • 102-page data dictionary, ≈100 elements

47. Surrogate measures There are useful surrogate measures for major screening outcomes. • Mortality • Incidence • Cost and cost-effectiveness • Acceptability • Quality • Program measures

48. The key measures (provisional) • Participation rate - acceptance • Test positivity rate - cost • Referral rate for colonoscopy – risk management • Downstaging – impact on mortality • Adenoma detection rate – impact on incidence • Colonoscopy quality measures • Program • Repeat participation rate • Incremental CPLYS, DALYs • Participant satisfaction • Follow-up of high risk groups • Workload impact • Later • Interval cancers