Population Screening for Colorectal Cancer - update of evidences

1. Dr Jennifer Lee PYNEH Population Screening for Colorectal Cancer- update of evidences

3. Screening – the principles

4. 3rd commonest cancer in US • 3rd leading cause of cancer death in both men and women in the US • Incidence: • Male: 57.2/100, 000 population • Female: 42.5/100,000 population Important common health problem ? American Cancer Society

5. Incidence: • Male: 47.1/100, 000 population • Female: 31.0/100,000 population Colorectal Cancer in Hong Kong (Hong Kong Cancer Registry )

6. 5 year survival: • 90% if disease diagnosed while still localized • 68% for regional disease • 10% if distant metastasis present Prognosis

7. Journal of InternalMedicine 270; 87–98 Natural history of disease : Pathogenesis

8. Screening modalities

10. Barium enema: not recommended by Asia Pacific Working Group

11. Evaluates rectum, sigmoid colon, descending colon Does not require sedation /full bowel preparation Shorter procedural time Can be done by trained nurse/physician assistants Cost: ~ USD 244 Flexible sigmoidoscopy

12. Gold standard for diagnosis • Requires bowel preparation and sedation • Potential risk of perforation and post-polypectomy bleeding • Cost: ~USD 450 • Efficacy: • No prospective, RCT of screening colonoscopy for incidence/ mortality reduction • Indirect evidence of incidence reduction in RCT of other screening test Colonoscopy

13. 170,432 individuals aged 55-64 randomized • No family history / colonic workup within 3 years / no bowel symptoms • Intervention group ( 57,237 ) vs controlled group (NO screening)(113,195) • 71% (40,674) had flexible sigmoidoscopy done • 5% referred for full colonoscopy due to high risk neoplasms • Participants flagged in national health registry for causes of death and colorectal cancer diagnoses • Follow up period: 11 years Lancet 2010; 375: 1624-33

14. Colorectal cancer detection rate: 3.5 / 1000 screened • All distal neoplasia (adenoma/cancer) 12% of screening group • In intention-to-treat analyses, colorectal cancer incidence in the intervention group was reduced by 23% and mortality by 31% • 23% of patients who had colonoscopy has proximal polyps • 5% advanced proximal adenomas • 0.4% proximal cancers • No significant effect on incidence of proximal colon cancers

15. Is this UK study applicable to Hong Kong?

16. Difference between east & west? Figures comparing 3 Caucasian populations studies VS 5 studies from Asian populations and Australia Sung et al, Gut 2008;57:1166–1176

17. 5464 colonoscopy performed; Mean age: 55.0 +/-15.5 year • Advanced neoplasm found in 512 patients (9.4%) • Carcinoma found in 322 patients (5.9%) • majority of colonic neoplasms are in distal colon • advanced neoplasm (65.1%) ; Cancer (71.1%) • Similar to western figures • Volume 64, No. 5 : 2006 GASTROINTESTINAL ENDOSCOPY

18. 2.2% of patients with advanced proximal neoplasm (including 1% cancer) will be missed by flexible sigmoidoscopy alone 61% of patients with advanced proximal lesions had no colonic neoplasm in the distal colon What are we missing?

19. Taiwan • asymptomatic Chinese • 1708 total colonoscopy performed • 263 (15.4%) had colorectal neoplasia; • 51 (3.0%) had advanced lesions • 125 (37.8%) were proximal in location • Two thirds (66.7%) of patients with proximal advanced lesions had no distal lesion • 1.8% of subjects without distal neoplasm had proximal advanced neoplasm • proportion of patients with proximal or proximal plus distal lesions increased with age (Volume 61, No. 4 : 2005 GASTROINTESTINAL ENDOSCOPY)

20. Perforations: • 1/40 332 flexible sigmoidoscopy • 4/2377 colonoscopy • All after snare polypectomy • 3 required surgery • Bleeding post- sigmoidoscopy: • 12 (8 after polypectomy); 1 required surgical treatment • Bleeding post colonoscopy: • 9 (all after polypectomy)

21. Single center 5593 colonoscopy case reviewed Polypecotomy done in 1657 cases Risk of post-polypectomy bleeding ~ 2.2% Hui AJ et. Al Gastrointest Endo 2004, 59(1):44-48 Post-polypectomy bleedinglocal data

22. What to choose? • Colonoscopy • Evaluates whole colon • Longer procedural time • Full bowel preparation • Cost • Potential complication related to sedation , polypectomy • Flexible Sigmoidoscopy • Shorter procedural time • No full bowel preparation • No sedation • Lower cost • Lower complication rate • More acceptable • May miss proximal lesions

23. 2010 Recommendation on CRC screening by Cancer Expert Working Group • Screening to be considered in individuals aged 50 to 75 with average risk • Annual/ biennial FOBT • FS every 5 years • Colonoscopy every 10 years Current recommendation in Hong Kong

25. 2D&3D images obtained by CT • Rapid advancement due to newer multi-detector CT • Non-invasive • Cost : ~ USD 800 • Efficacy: • No RCT to demonstrate incidence / mortality reduction • Sensitivity for large polyps >1cm: ~ 85-93% • Small polyps (6-9mm): ~70-86% • Sensitivity for invasive cancer: 96% CT colonography (Virtual colonoscopy) Eur Radiol (2012) 22:1495–1503 Margriet C. de Haan et al.

26. higher diagnostic yield per 100 invitees than primary gFOBT and FIT screening • similar yield as sigmoidoscopy and colonoscopy screening • Not therapeutic • per-patient false-positive rates: • polyps >6mm : 3.6% • polyps >10-mm : 2.1% • Cost-effectiveness unknown • ?Impact of detecting extracolonic disease • Colonoscopy to be offered if largest polyp detected >6mm • Recommended for individuals who decline colonoscopy/not good candidate for colonoscopy CT colonography Margriet C. de Haan et al. Eur Radiol (2012) 22:1495–1503 David H. Kim , et al. Radiology(2012),254, 493-500

27. No need for sedation / air insufflation / radiation exposure • NOT therapeutic • Cost: ~USD 950 • Results affected by • Bowel preparation • Colonic transit time • Battery life Colon capsule endoscopy

28. Sensitivity for cancer : 74% • Polyp and cancer pick up rate: inferior than colonoscopy • False positive rate: 33% • Future improvement ? Colon capsule endoscopy Gossum, et al, N Engl J Med 2009;361:264-70 Rokkas, et al, Gastrointest Endosc 2010;71:792-8

29. Colorectal cancer screening is important Recent large scale population randomised study in UK suggest flexible sigmoidoscopy is effective for screening However ~2% proximal lesions may be missed Newer modalities such as CT colonography and colon capsule endoscopy is a viable alternative, but needs further evaluation for effectiveness as screening tool Summary

30. Thank you

31. Aliment Pharmacol Ther 28, 353–363 Cost-effectiveness of screening • Hypothetical population of 100, 000 population for screening • annual FOB / 5 yearly FS / 10 yearly Colonoscopy • Screening at age 50 until 80 • Cost of treatment including chemotherapy calculated • incremental cost-effectiveness ratio (Cost per life year saved)

33. UK trial: longeset period FU, 11 years • Norwegian Colorectal Cancer Prevention (NORCCAP) trial , inter-rim report 6 years • Reduce mortality only, no observaed reduced incidence so far (since early peak of screening detected cancer) • Populations study • Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial in the USA • Italian Screening COlon REtto (SCORE): follow UK protocol Flexible sigmoidoscopy

34. Primary screening colonoscopy: Poland, Germany • Randomized trials for screening colonoscopy: • Spanish trial, 55 000 individuals between 50 and 69 years of age are being randomly assigned to either iFOBT or colonoscopy • final results are expected in 2021 after 10 years of follow-up • Nordic–European Initiative on Colorectal Cancer (NordICC) is a multicentre, multinational randomisied trial • 66 000 individuals are randomly assigned to either colonoscopy or no screening • Planned 15-year follow-up • an interim analysis after 10 years due around 2022 Colonoscopy

35. High-risk criteria: • 1 cm or larger • three or more adenoma • tubulovillous or villous histology • severe dysplasia or malignant disease • 20 or more hyperplastic polyps above the distal rectum Referal for colonoscopy