Bangkok,

Thailand

CanalAVIST Medical Forum

19 September 2008

Title : Colorectal cancer screening, an Asian perspective

Speaker : Dr Taya Kitiyakara Department of

Gastroenterology Faculty of

Medicine Ramathibodi

Hospital, Mahidol

University

Time : 09:00 (TH)

Bangk

ok, Thaila

ndDr Taya Kitiyakara graduated from St Mary’s Hospital,

Imperial College, London 1996 after attending Cambridge University for BA in Medical sciences. He was at

King’s college Hospital, London for his Senior House Officer (residency)

Medical rotation up to 2000.

He trained in Gastroenterology in Oxford, 2000-2007, with one year of liver transplantation at the Royal Prince Alfred Hospital,

Sydney, Australia in 2004.

He has recently started as consultant Gastroenterologist at Ramathibodi Hospital, Mahidol

University, Bangkok, Thailand.CanalAVIST Medical Forum

19 September 2008

Colorectal cancer screening, an Asian perspective

Dr Taya Kitiyakara Dept of gastroenterology

Faculty of medicineRamathibodi hospital

Mahidol University

Content

Incidence Investigations/ screening tests Implementation/ strategies Improvements

Incidence

Incidence of colorectal cancer is high

Second leading cause of cancer death in the West.

Estimated 49,960 deaths in USA, 2008 Jemal et al Cancer J Clin 2008

Incidence of colorectal cancer in Asia

Sung et al Lancet 2005

Increasing incidence of colorectal cancer in Asia

Increasing incidence of colorectal cancer in Asia

– ‘Westernisation’ of diet and lifestyle– Increasing life expectancy

H Sriplung et al 2006

J Ferlay et al 2004KS Chia et al 1995L Yang et al 2004

Increasing mortality from colorectal cancer in Asia

Decreasing mortality in western world

Increasing mortality in Asia

Sung et al Lancet 2005

Mortality rates: men

Mortality rates: women

Screening is appropriate colorectal cancer

Natural history Early detection Treatment available and acceptable Change in outcome

R Rerknimitr et al 2006

Evidence for efficacy of screening

Author type Initial test/ 2nd line

n= f/u (mean)

% CRC reduction

Mandel 1993

RCT FOB/

Colonoscopy46,551 13 yrs 33%

Hardcastle 1996

RCT FOB/

Colonoscopy152,850 7.8yrs 15%

Kronborg 1996

RCT FOB/

Colonoscopy61,833 10 yrs 18%

Winawer et al 1993

Historical controls

Colonoscopy 1418 5.9 yrs 90-76%

EFFICACY OF SCREENING- colonoscopy

Colonoscopy used in all other screening modalities to remove polyps and confirm CRC

Gupta et al 2005

Asia Pacific consensus recommendations

GUT 2008

Investigations and screening tests

Understanding screening

National screening Individual screening

High risk vs. average risk screening

asymptomatic

Tests available for screening

Stool tests– Faecal occult blood (guaiac based)– Faecal occult blood (immunobased)– Stool DNA testing

Imaging tests– Barium tests– CT colonography

Endoscopy tests– Flexible sigmoidoscopy– Colonoscopy

Understanding tests

Tests for (mainly) early cancer– Stool tests

Tests for polyps and cancer– Colonoscopy,– CT colonography,– DCBE

Joint Guideline , US Multi-society task force on colorectal cancer 2008

Stool tests: FOB tests

FOBT sensitivity variable depending on type (high with Hemoccult SENSA)

Higher sensitivity = lower specificity Requires annual/biennial testing Further colonoscopy needed if positive Acceptable test to initiate screening

Detects Collection Cost One-time SENS/SPEC for CRC

gFOB pseudoperoxidase complicated cheap (37-79%) / (87-98%)

FIT Human globin easier More expensive

(65-94%) / (87-97%)

FOB in screening studiesFOB typeN=screened

uptake positive +predictive value

Hardcastle et al, lancet 96

Hemoccultn= 152,850

59.6-38% 2.1% 12% CRC46% neoplasia

Kronborg et alLancet 96

Hemoccult IIn=61,833

67% 1.0% 11% CRC27% adenoma >1cm

Mandel et alNEMJ 93

HemoccultN=46,551

90.2-46% 2.4% 5.6% for CRC

Uk 1st round screen

Hema-screenN=478,000

56.8% 1.9% 10.9% cancer 35% adenoma

Sung et al Gastroent 03

Hemoccult IIN=505

all 20% 8.9% advanced lesions 28.7% neoplasia

Sumetchotimaytha et al 2007

Hema-screen n=20,377

all 12.6% 0.8% CRC3.4% polyps

Li et al Chin Med J 2003

FOBTN= 26,827

74% 35.6% 0.2% CRC0.59% Adenoma

Immunochemical FOB may be better in Asia

FOB+ FIT+ SENS FOB

SENS FIT

SPEC FOB

SPEC FIT

+ predict value FOB

+predict value FIT

Sumetchotimaytha et al 2007

12.6%Hemascreen

12.8% Occultech

0.8% CRC3.4% polyps

1.1% CRC8.9% polyps

Li et al 2003 35.6% 5.6% 0.2% CRC0.6% adenomas

Not specified(at best 1.3% CRC3.7% adenomas)

Wong et al 2007

41% 14% 100% 89% 70% 94% 16% CRC 42% CRC

Cost-effectiveness: Cost of tests + false positive test

Dietary manipulation is thought difficult in many Asian countries

Understanding sensitivity

Per Test sensitivity

(screening) programme sensitivity for test– Repeated chance of detecting lesion– May be better at detecting rapidly growing

cancer compared to an infrequent test

Ransohoff Gastroenterology 2005

Imaging- double contrast barium enema

No RCT/ major trials showing reduction in CRC mortality

Interval not determined

Decreasing use Labour intensive Training issues

Radiation

Superceded by CT colonography

CT colonography

Imaging tests- CT colonography

CT colonography not in Asia Pacific recommendations.

Increasing use/availability More acceptable than

colonoscopy

Extra-luminal imaging

Costly Radiation Flat/ depressed lesions

difficult to image

Criteria needed for best sensitivity:– Excellent bowel prep– Fecal tagging– Cutting edge equipment– Analysis of both 2D and

3D images– Experience of radiologist

Castells Gastroenterology 2008

CT colonography- detection rate

Sensitivity of CT colonography compared to 2 colonoscopies.

2nd colonoscopy aware of all lesions detected from CT and initial colonoscopy

Minimised known miss rate- true sensitivity of CT results

All polyps

>6mm

Neoplastic >6mm

Neoplastic >10mm (n=7)

All polyps All neoplastic

Second colonoscopy

100% 100% 100% 100% 100%

Initial colonoscopy

84%

(69-92%)

91%

(71-97%)

86%

(49-97%)

83%

(74-89%)

87%

(73-94%)

CT colon

(3 observers)

86%

(72-94%)

81%

(60-92%)

100%

(70-100%)

63%

(53-72%)

64%

(48-77%)

Iannaccone et al 2005

Endoscopic tests

Flexible sigmoidoscopy

Decreasing numbers performed in USA ‘incomplete test’ Miss proximal lesions False sense of reassurance

Benefit of cost-effectiveness vs thoroughness may be lost to screenee

Legal implications? Quality of procedure very variable in studies.

Colonoscopy- advantages

‘Complete’ test 10 yr interval Expected 90-70% reduction in CRC

mortality

Colonoscopy- disadvantages Expensive Time and labour intensive May be least acceptable of screening tests Recognised complications Miss rates and interval cancers

Ransohoff Gastroenterology 2005

Miss rates in back-to-back studies

Heresbach et al Endoscopy 2008

Van Rijn et al Am J Gastro 2006

Kaltenbach et al Gut 2008

Iannaccone et al Radiology 2005

Year , n= All polyps Adenomas 5-10mm

Adenomas >10mm or advanced

Systematic review (6 studies)

<2004, n=465 21% 13% 2% (0.3-7.3%)

Multi-centre study

2001-2005, n=286 28% 9% 11%

Double colonoscopy with CT colon

2002-2003, n=88 36% 17% 13% (6-17%)

single centre study vs. NBI

2006-2007, n=142 13% 9.5% 0% (0-1.1%)

Quality control requirements for screening

Bowel prep Training/experience Complete insertion rate Withdrawal time/technique and polyp

detection rate Proper consent Complete polyp removal Timely detection and appropriate

management of complications Follow-up protocol

Joint Guideline , US Multi-society task force on colorectal cancer 2008

Implementation

+ = ?

FOB may be most cost-effective screening test in Asia

Chinese study, Markov model, comparing gFOB, FS, and colonoscopy (population age 50-80yrs)

Colonoscopy used if initial test positive Colonoscopic screening reduced CRC the most (54.1%)

FOB is most cost-effective (then colonoscopy ,then FS) – US$ 6222 /life year saved

FOB remains most cost-effective with different compliance to screening, but not if sensitivity is 30-60%, and specificity is 20-50%

Tsoi et al APT 2008

Large variability in compliance in Asia:Population screening studies

Japan Taiwan China UK 2ND ROUND

France

Health care system

1/3 FIT cost paid by screenee

Combined screening of 5 cancers

Pay system not specified

NHS state funded

State funded

N= 35,602,782 26,008 26,827 127,746 182,274

Test FIT FIT FOB/FIT FOB FOB

Uptake 17% 82% 74% 52.1% 55.4%

Positive test(of returned tests)

7% 5.6% 35.6/5.6% 1.77% 3.4%

%follow up colonoscopy

58% 68% 7.1% 82.8% 87.9%

% with CRC of participants

0.16% 0.19% 0.07% 0.094% 0.23%

Saito 2006Yang et al 2006Li et al 2003Weller et al 2007Denis et al 2007

Compliance, understanding and barriers to screening

Public knowledge of CRC is poor

Lack of time, financial constraints Lack of physician’s recommendation

Lower knowledge about cancer and screening tests less likely to screen

Tests – embarrassing

No health insurance ‘Ostrich’ strategy

Popular support from press and public figures

Sung et al 2008

Ransohoff et al 2005

Resource available?

400 endoscopy units in Thailand

(if FOB Japanese rates from Saito 2006 used )

=126,405 colonoscopies needed

= 316 additional colonoscopies/ unit

Not counting further surveillance colonoscopies needed

Men aged 50-70yrs

4,993,425

Women aged 50-70yr

5,628,906

Total 10,622,331

Total aged 49yrs

821,922

National database 2007Department of Provincial AdministrationMinistry of Interior Thailand

Targeted/ stratification screening

Selective screening for high risk patients?

Increased risk for those with FH of CRC

‘Relaxed’ FH screening guideline may be of benefit

RISK SCORING for deciding initial test

– Using age/ sex/ FH or distal findings

– Reducing number of colonoscopy required by 40%

– Detecting 89-92% of CRCs

Johns et al Am J Gastro 2001

Lin et al Gastroenterology 2006Imperiale et al Ann Intern Med 2003

Subramanian et al Colorectal Dis 2008

Preparation for screening in UK ‘Fitness to scope’

Capacity evaluation Audits

– Complete caecal intubation rate (national)

– Improving endoscopy list efficiency

Global rating score ‘Driving’ test National endoscopy

training centres JAG accreditation Funding incentives

Nnoaham et al Gut 2008

Pickard et al Colorectal dis 2006

Bowles et al Gut 2004Ball et al BMJ 2004

www.grs.nhs.uk

Improvements

New technologies; too new

New endoscopic equipment: – High definition/ Digital chromoendoscopy

eg. NBI (Olympus), i-scan (Pentax) – confocal microendoscopy

Capsule endoscopy (colonic setting)

Fecal DNA

Flat/ depressed lesion detection

Recognised in Japan for many years

Recently accepted in the west Difficult to detect

Higher proportion of high-grade dysplasia/ carcinoma

May be one factor for interval cancers

Muto et al Dis Colon Rectum 1985

Kudo et al World J Surg 2000Soetikno et al JAMA 2008

Rembacken et al Lancet 2000

Improvement in already available techniques

Endoscopic

Patient education

Physician education- referral/ follow-up

General satisfaction

East et al APT 2008

Sung et al Am J Gastro 2008

Turner et al J Gen Intern Med 2003

Endoscopy Units should strive for quality assurance

Audit cycles Local rates eg. for cecal intubation, polyp

detection, interval cancers, complications

Appropriate indication and intervals for procedures according to guidelines (improving cost-effectiveness)

Training in detecting flat polyps Consenting Training trainers/trainees

National programmes should adapt to the country

Resource Geography Patient acceptance/education Healthcare system and infrastructure Funding of screening

More research needed

Evidence to base national programme and Policies– Uptake of each screening modality?– Barriers to screening in each country?– Dietary restrictions for FOB possible?– Possibility of mixed strategies or targeted

screening?– Pilot studies.– Increase in number of colonoscopist/ pathologist/

surgeons needed?

Summary

Incidence of colorectal cancer in Asia in rising

Screening reduces mortality from CRC

Screening tests available include FOB, CT colonography, colonoscopy

Per-test sensitivity vs per- programme sensitivity (which require infrastructure to ensure repeat testing)

Summary

Education, reduction in barriers, encouragement by physicians needed

Quality assurance is needed for colonoscopy and CT colonography

Resource may be a limitation

Stratification or mixed strategies may be more cost-effective

Pilot studies in screening general population likely to be needed- up-take/ capacity/ cost-effectiveness for each country

Bangk

ok, Thaila

nd

CanalAVIST Medical Forum

19 September 2008

End of Presentation

by

Dr Taya Kitiyakara