ScreeningScreeningfor Colorectal Cancer (CRC)for Colorectal Cancer (CRC)

Nov, 2007Nov, 2007

A Aljebreen, FRCPCDivision of Gastroenterology

KKUH, Riyadh

Colorectal cancer (CRC)Colorectal cancer (CRC)

CRC: FactsCRC: Facts

Who should be screened?Who should be screened?

Average vs high risk patientsAverage vs high risk patients

Which screening test (FOBT vs Which screening test (FOBT vs sigmoidoscopy vs Ba enema vs CT sigmoidoscopy vs Ba enema vs CT colonoscgraphy or colonoscopy)colonoscgraphy or colonoscopy)

RecommendationsRecommendations

CRC: Adenoma-carcinoma sequenceCRC: Adenoma-carcinoma sequence

Normal ColonNormal Colon Advanced Advanced AdenomaAdenoma

10-20% Lifetime Risk

Genetic Environmental Lifestyle

5-6% Lifetime Risk

This progression probably takes at least 10 years in most people

National Polyp StudyNational Polyp Study: : 76-90% reduction in Cancer 76-90% reduction in Cancer incidence after polypectomyincidence after polypectomyNEJM1993;328:901-6.

CRC and colorectal adenomas: CRC and colorectal adenomas: How common?How common?

Colorectal cancer (CRC) is a worldwide Colorectal cancer (CRC) is a worldwide problem, with an annual incidence of problem, with an annual incidence of approximately 1 million cases and an approximately 1 million cases and an annual mortality of more than 500,000.annual mortality of more than 500,000.

CRC is the second most common cause of CRC is the second most common cause of cancer mortality among men and women.cancer mortality among men and women.

CRC and colorectal adenomas: CRC and colorectal adenomas: How common?How common?

According to the last National Cancer Registry According to the last National Cancer Registry report in Saudi Arabia (2001), CRC was ranked report in Saudi Arabia (2001), CRC was ranked as the 3as the 3rdrd. . There is no clear data about prevalence of There is no clear data about prevalence of colorectal adenoma in Saudi population >50, colorectal adenoma in Saudi population >50, however, small retrospective studies showed however, small retrospective studies showed that prevalence of colorectal adenoma among that prevalence of colorectal adenoma among symptomatic patients were 18-25%. symptomatic patients were 18-25%.

Unsedated colonoscopy, Saudi Journal of Gastro 2003

KKUH experience: CRC KKUH experience: CRC

Average age was 55 yrAverage age was 55 yr

50% presented with complete Large bowel 50% presented with complete Large bowel obstruction.obstruction.

35% already had mets.35% already had mets.

(72%) already stage C or D(72%) already stage C or D

Saudi Journal of Gastro, 2007.Saudi Journal of Gastro, 2007.

Screening of CRC Screening of CRC

It is complex, it requires:It is complex, it requires:– considerable patient effort (fecal occult blood considerable patient effort (fecal occult blood

test slides, colonoscopy preparation, etc.), test slides, colonoscopy preparation, etc.), – sedation and sedation and – a health-care partner for some tests. a health-care partner for some tests.

Successful screening programs:Successful screening programs:Requirements?Requirements?

awareness awareness

recommendation from the primary-care recommendation from the primary-care physician (national guidelines), physician (national guidelines),

patient acceptance,patient acceptance,

financial coverage, financial coverage,

risk stratification, risk stratification,

screening test, screening test,

timely diagnosis, timely diagnosis,

timely treatment, and timely treatment, and

appropriate follow-up.appropriate follow-up.

CRC: FactsCRC: Factsscreening rates remain low!!screening rates remain low!!

<30% of eligible persons have had a screening <30% of eligible persons have had a screening test for CRC in western countries.test for CRC in western countries.

Risk Factors for CRCRisk Factors for CRC

Sporadic/ Sporadic/ Average Risk Average Risk 75%75%

Family History 15-20%

HNPCC 5% FAP-1%

IBD-1%

Who should be screened?Who should be screened?

Who is High Risk?Who is High Risk?

Familial Polyposis Familial Polyposis – Sigmoidoscopy inSigmoidoscopy in

teenage years teenage years

– Colectomy Colectomy

HNPCC HNPCC – Colonoscopy in 20’s Colonoscopy in 20’s

Family History: Family History: – Colonoscopy 10 years younger thanColonoscopy 10 years younger than

index family case index family case

APC Mutation

Mismatch Repair Genes

Clinical problemClinical problem

A healthy 50-year-old woman at average risk for colorectal cancer (i.e., age is her only risk factor) is scheduled to undergo a periodic examination.

Which screening test for colorectal cancer should be recommended?

Which test?Which test?

Ideal Screening: Target high-risk patients BEFOREBEFORE they develop cancer

FOBT

FOBT

Sigmoidoscopy

Colonoscopy

Fecal Occult-Blood TestingFecal Occult-Blood Testing

Sensitivity 24%Sensitivity 24%

The reduction in mortality risk (15 -33%)The reduction in mortality risk (15 -33%)

Recommendation (average risk patient)Recommendation (average risk patient) – Offer yearly screening with FOBT.Offer yearly screening with FOBT.– Patients with a positive test on any specimen Patients with a positive test on any specimen

should be followed up with colonoscopy. should be followed up with colonoscopy.

Hardcastle et al. Lancet 1996;348: 1472–1477. Kronborg et al. Lancet 1996;348:1467–1471.

What about What about genetic testing?genetic testing?

Stool Genetic TestsStool Genetic Tests33 pts with neoplasia and 28 without33 pts with neoplasia and 28 without

–Mutations: K-ras, p53, APC –Microsatellite instability marker (Bat-26)

76

78

80

82

84

86

88

90

92

94

Sensitivity Specificity

CA

adenoma

>1cm

Ahlquist et al; Gastroenterol 2000; 119:1219-27

However, However,

The optimal set of molecular markers The optimal set of molecular markers remains to be determined, and remains to be determined, and

The feasibility of such tests when applied The feasibility of such tests when applied to the general population is yet unknown. to the general population is yet unknown.

Sigmoidoscopy- U.S. StudiesSigmoidoscopy- U.S. Studies

Sensitivity* for Advanced Neoplasia: 50-70%70%

NEJM 2000; 343: 162-8; 169-74

More than 50% of proximal lesionsNot Not detected

1. If all pts with adenoma on sigmoidoscopy, undergo colonoscopy that means 25% of pts will need colonoscopy

2. Less effective with increasing age

3. Recommendation: offer sig every 5 years, if any abnormality, do colonoscopy

?Combination of FOBT +sig?Combination of FOBT +sig

D Liberman et al, NEJM Aug 2001

Ba enemaBa enema

The sensitivity rate was – 32% in which the largest adenomas detected

were <0.5 cm, – 53% for those e adenomas 0.6 to 1.0 cm, and– 48% for those > 1.0 cm.

Recommendations:Recommendations:– Offer Ba enema every 5 years

WINAWER et al, NEJM 2000;342:1766-72.

Colonoscopy Colonoscopy Best test for polyp detection (95% Sen Best test for polyp detection (95% Sen and 95% Sp)and 95% Sp)

Need once every 10 years (attractive!)Need once every 10 years (attractive!)

Best test for cancer preventionBest test for cancer prevention

Invasive (2/1000 risk of perforation) Invasive (2/1000 risk of perforation)

Costly Costly

Requires highly qualified endoscopistRequires highly qualified endoscopist

Recommendation:Recommendation: offer colonoscopy offer colonoscopy every 10 yearsevery 10 years

Problems Problems

The miss rate for polyps is 15–25% for The miss rate for polyps is 15–25% for adenomas smaller than 5 mm in diameter adenomas smaller than 5 mm in diameter and 0–6% for adenomas of >10 mm. and 0–6% for adenomas of >10 mm.

How to overcome this problem?How to overcome this problem?– Obtain a clear informed consentObtain a clear informed consent– Document cecal intubationDocument cecal intubation– Good prepGood prep– Take your time during withdrawals (6 minute rule)Take your time during withdrawals (6 minute rule)– Others (not yet!)Others (not yet!)

Average-Risk Screening: Average-Risk Screening: What is the “best” test?What is the “best” test?

Mortality Cancer TEST Issues Sensitivity Reduction Prevention FOBT Needs annual test 30% 30% +

Sigmoid Misses proximal lesions 70% 50-60 % ++

Barium No evidence 48% ?? 50% ++

Colonoscopy Expensive 99% 75-80% ++++

Emerging Screening Tests

Virtual colonoscopyVirtual colonoscopy

Virtual colonoscopyVirtual colonoscopy

Sensitivity Sensitivity – 35-96% for polyps>1cm35-96% for polyps>1cm

False positive rates of 17%False positive rates of 17%Miss flat lesionsMiss flat lesionsInter-observer variabilityInter-observer variabilityNeed prep + air insufflationNeed prep + air insufflationRadiation exposureRadiation exposureCostCostIssue of when to refer to colonoscopy?Issue of when to refer to colonoscopy?Ready????

Pickhardt et al NEJM 2003;349:2191-200.Fenlon et al, NEJM 1999;341:1496–1503.Yee et al, Radiology 2001;219:685–692.

Cost-effectiveness of CRC screening Cost-effectiveness of CRC screening

All standard options for CRC screening in All standard options for CRC screening in average-risk individuals are cost-effective.average-risk individuals are cost-effective.

They are as cost-effective as They are as cost-effective as mammography and mammography and

more cost-effective than other forms of more cost-effective than other forms of medical screening (e.g., for cholesterol in medical screening (e.g., for cholesterol in hypertension). hypertension).

WGO Recommendations: 2007WGO Recommendations: 2007

Cascade 1: Countries with high level of Cascade 1: Countries with high level of resources (financial, professional, resources (financial, professional, facilities) and high colorectal cancer facilities) and high colorectal cancer incidence and mortality. incidence and mortality. – People at average risk: Colonoscopy for People at average risk: Colonoscopy for

average-risk men and women, starting at the average-risk men and women, starting at the age of 50 and every 10 years.age of 50 and every 10 years.

Cascade 2-6: when limited colonoscopy Cascade 2-6: when limited colonoscopy and or flex sig resources.and or flex sig resources.

RECOMMENDED TESTS IN PERSONS AT AVERAGE RISK FOR CRC

Colon Cancer Screening Recommendations for People With Familial or Inherited Risk

CONCLUSIONS

Detection and removal of adenomas can prevent most colon cancersThe variation in recommendations should not obscure the larger message that screening can reduce the rate of death from colorectal cancer. The variation should be interpreted in a positive way as giving clinicians several choices with respect to colorectal- cancer screening (availability, cost, safety, and quality)

CONCLUSIONS

At present physicians should not be dogmatic about which test to use but, rather, should offer patients a choice among FOBT, sig & colonoscopy.

They should discuss the features of each test with their patients, who may have their own perspectives and preferences (cost, safety, discomfort, and fear of cancer)

CONCLUSIONS

Patients should be told about lifestyle measures that may reduce the risk of colorectal cancer, including– avoiding obesity, – exercising regularly, – not smoking,– and limiting their intake of alcohol and red

meat.