Dr Jennifer LeePYNEH

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

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

Incidence: Male:

47.1/100, 000 population

Female: 31.0/100,000 population

(Hong Kong Cancer Registry )

5 year survival: 90% if disease diagnosed while still

localized 68% for regional disease 10% if distant metastasis present

Journal of InternalMedicine 270; 87–98

Sensitivity Evidence Recommendation

Faecal Occult Blood

37.1% – 79.4% RCT provenMortality ↓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

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

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

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 yearsLancet 2010; 375: 1624-33

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

Is this UK study applicable to Is this UK study applicable to Hong Kong?Hong Kong?

Asia West

Polyps Proximal 30% 49%

Distal 57% 49%

Synchrounous

13% 2%

Advanced Neoplasia

Proximal 29% 35%

Distal 52% 59%

Synchronous 19% 6%

Figures comparing 3 Caucasian populations studies VS 5 studies from Asian populations and Australia

Sung et al, Gut 2008;57:1166–1176

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

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

•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)

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)

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

Flexible Flexible SigmoidoscopySigmoidoscopy

Shorter procedural timeShorter procedural timeNo full bowel No full bowel preparationpreparationNo sedationNo sedationLower costLower costLower complication rateLower complication rateMore acceptableMore acceptable

•May miss proximal May miss proximal lesionslesions

ColonoscopyColonoscopy

Evaluates whole colonEvaluates whole colon

•Longer procedural timeLonger procedural time•Full bowel preparationFull bowel preparation•CostCost•Potential complication Potential complication related to sedation , related to sedation , polypectomypolypectomy

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

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.

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

Margriet C. de Haan et al. Eur Radiol (2012) 22:1495–1503

David H. Kim , et al. Radiology(2012),254, 493-500

No need for sedation / air insufflation / radiation exposure

NOT therapeutic Cost: ~USD 950 Results affected by

Bowel preparation Colonic transit time Battery life

Sensitivity Specificity

Gossum, et al Polyps >6mm 64% 84%

Advanced adenoma

73% 79%

Rokkas, et alMeta-analysis626 CCE

Significant polyps(size >6mm / no.>3)

69% 86%

All polyps 73% 89%

Gossum, et al, N Engl J Med 2009;361:264-70

Rokkas, et al, Gastrointest Endosc 2010;71:792-8

• Sensitivity for cancer : 74%• Polyp and cancer pick up rate: inferior than

colonoscopy• False positive rate: 33%• Future improvement ?

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

Aliment Pharmacol Ther 28, 353–363

•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)

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

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

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