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

3. Screening – the principles
World Health Organization Criteria
Important common health problem
Natural history of disease adequately understood and there is asymptomatic early disease stage
Treatment available
Diagnostic tool available
Cost-effective and competent follow-up programs available

4. Important common health problem ?
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
American Cancer Society

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

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

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

8. Screening modalities

9. Screening Modalities Stool based Faecal Occult Blood Test
Faecal Immunochemical Test
Stool DNA
Structural Exam
Flexible sigmoidoscopy
Colonoscopy
Double contrast Barium Enema
CT colonography
Colon capsule endoscopy

10. Sensitivity
Evidence
Recommendation
Faecal Occult Blood
37.1% – 79.4%
RCT proven
Mortality ↓15-33%
Incidence ↓20%
Annually screening
Faecal Immunochemical test
81% - 94%
Stool DNA
52%-91% ?
Barium Enema
Cancer: 85-97%
Adenoma>1cm: ~48%
5 years*
Barium enema: not recommended by Asia Pacific Working Group

11. Flexible sigmoidoscopy
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

12. Colonoscopy 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

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:
>1cm
3 or more adenomas
Severe dysplasia / villous type
>20 hyperplastic polyps at distal colon

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
Asia
West
Polyps
Proximal
30%
49%
Distal
57%
Synchrounous
13% 2%
Advanced Neoplasia
29%
35%
52%
59%
Synchronous
19% 6%
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. What are we missing?
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

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. Bleeding post- sigmoidoscopy: Bleeding post colonoscopy:
Perforations:
1/ 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. Post-polypectomy bleeding local data
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

22. What to choose? Colonoscopy Flexible Sigmoidoscopy
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. Current recommendation in Hong Kong
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

25. CT colonography (Virtual colonoscopy)
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%
Eur Radiol (2012) 22:1495–1503 Margriet C. de Haan et al.

26. CT colonography
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
Patients with false-positive findings were those who were sent for OC and had findings of a nonadenomatous (hyperplastic or mucosal) polyp or had a polyp that was not seen. 
Margriet C. de Haan et al. Eur Radiol (2012) 22:1495–1503
David H. Kim , et al. Radiology(2012),254, 

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

28. Colon capsule endoscopy
Sensitivity
Specificity
Gossum, et al
Polyps >6mm
64%
84%
Advanced adenoma
73%
79%
Rokkas, et al
Meta-analysis
626 CCE
Significant polyps
(size >6mm / no.>3)
69%
86%
All polyps
89%
Sensitivity for cancer : 74%
Polyp and cancer pick up rate: inferior than colonoscopy
False positive rate: 33%
Future improvement ?
Rokkas: A total of 626 individuals were included in this meta-analysis.
Gossum, et al, N Engl J Med 2009;361:264-70
Rokkas, et al, Gastrointest Endosc 2010;71:792-8

29. Summary 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

30. Thank you

31. 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)
Aliment Pharmacol Ther 28, 353–363

33. Flexible sigmoidoscopy
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

34. Colonoscopy 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

35. Referal for colonoscopy
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