Dennis J. Ahnen MD, AGAF, FACGDennis J. Ahnen MD, AGAF, FACG

Colorectal CancerThe Preventable Killer

Relevant Conflicts of InterestCo-Investigator (past)- CRC screening trial for stool DNA testCo-Investigator (current)- CRC Screening trial of colonoscopy vs FITCo-Author- Modeling studies commissioned by ACS for current guidelines

Dennis J. Ahnen, MD, AGAF, FACGDirector Genetics Clinic, Gastroenterology of the Rockies

Professor Emeritus, University of Colorado School of Medicine

Colorectal Cancer is the result of a sequence of biologic events; It is

• Common• Lethal• Preventable

Dennis J. Ahnen MD, AGAF, FACGDennis J. Ahnen MD, AGAF, FACG

Colorectal CancerThe Preventable Killer

What is Colorectal Cancer?

Normalepithelium

Abnormalepithelium

Smalladenoma

Largeadenoma

Coloncarcinoma

10-15 Years

The Adenoma Carcinoma Sequence

Lung

CRC

145,600

Other

Prostate

Breast

United StatesNew Cases- 1,762,450

CRC is Common

Breast

LungProstate

CRC

212

WyomingNew Cases- 2580

Other

Siegel R: Source:-SEER 9 delay-adjusted rates, 1975-2012; 2-yr moving average.

0

2

4

6

8

10

12

14

1975

-76

1981

-82

1987

-88

1993

-94

1999

-00

2005

-06

2011

-12

Men

Women

51% since 1994

0

50

100

150

200

250

300

1975

-76

1981

-82

1987

-88

1993

-94

1999

-00

2005

-06

2011

-12

Inci

denc

e ra

te p

er 1

00,0

00

Men

Women

Ages 50+ Ages 20-49

40% since 1987

CRC Incidence Over TimeThe Good and Bad

Inci

denc

e/10

0,00

0

Inci

denc

e/10

0,00

0

≈15,000 new YO-CRCs

1975 1985 1995 2005 2015 1975 1985 1995 2005 2015

PresenterPresentation NotesNote difference in axis

CRC Risk Factors Demographic

• Country of origin• Age• Sex• Race/Ethnicity• SES• Family History

Fold

Ris

k

Lifetime Risk 5%

Screening Intensity

Family History and CRC Risk

Chart1

1 FDR/Ca

1 FDR < 50

2 FDR/Ca

>2 FDR/Ca

Lynch

Relative risk

2.5

4

3.5

8

9.5

Sheet1

1 FDR/Ca1 FDR < 502 FDR/Ca>2 FDR/CaLynch

Relative risk2.543.589.5

CRC Risk Factors Demographic

• Country of origin• Age• Sex• Race/Ethnicity• SES• Family History

Lifestyle• Obesity• Low Physical Activity• Smoking• Alcohol

Diet• High Red/Processed Meat• Low Fiber Containing foods

•Fruits and Vegetables

Failure to Get Screened

Lung

CRC

50,260

BreastProstate

Other

Pancreas

United StatesDeaths- 606,880

CRC is LethalWyoming

Deaths- 938

LungCRC

91

BreastProstate

Other

Pancreas

CRC Staging

5 year survival

80-95%70-75%

30-65%

CRC is Preventable- Modifable Risk FactorsDemographic

• Country of origin• Age• Sex• Race/Ethnicity• SES• Family History

Lifestyle• Obesity• Low Physical Activity• Smoking• Alcohol

Diet• High Red/Processed Meat• Low Fiber Containing foods

• Low Fruit and Vegetable

Modifiable

xxCRC Prevention

Risk Factors Demographic

• Country of origin• Age• Sex• Race/Ethnicity• SES• Family History

Lifestyle• Obesity• Low Physical Activity• Smoking• Alcohol

Diet• High Red/Processed Meat• Low Fiber Containing foods

• Low Fruit and Vegetable

Protective Factors• Aspirin for selected groups• Screening

CRC Screening- Risk Groups• Average risk

• No personal or FH of colonic neoplasia or IBD • Start CRC screening at age 45/50, stop at age 75-85• Options for screening

• hsFOBT/FIT- annually • FIT/DNA- every 3 years• Flexible Sigmoidoscopy- every 5 years• CT Colonography- every 5 years• Colonoscopy- every 10 years

• If done- CRC cases and deaths by 60-80%

Current Screening Guidelines• USPSTF 2016- “recommends CRC

screening starting at age 50 years and continuing until age 75…. multiple screening strategies to choose from” (A recommendation) Individualize screening age 76-85

• ACS 2017- Repeated modeling studies using current incidence and mortality rates for the young. 0

2

4

6

8

10

12

14

1975

…

1981

…

1987

…

1993

…

1999

…

2005

…

2011

…

Men

Women

Ages 20-49

Inci

denc

e/10

0,00

0

1975 1985 1995 2005 2015

• Conclusion- starting at age 45 led to a 4-8% decrease in number of new CRCs, and an 8-11% decrease in CRC deaths with a 12-17% increase in the number of colonoscopies needed, compared to starting at age 50.

Screening at 45 is Cost-Effective• Modeling cost-effectiveness of starting CRC

screening at 45 vs 50• Threshold for acceptable cost- $100,000/QALY gained

• If colonoscopy used throughout• $33,900/QALY gained

• If FIT used throughout• $7,700/QAYL gained

• If FIT from 45-49 then colonoscopy• $2,500/QALY gained- a bargain

Ladabaum et al Gastroenterology 2019

Current Screening Guidelines• USPSTF 2016- “recommends CRC screening starting at

age 50 years and continuing until age 75…. multiple screening strategies to choose from” Individualize screening age 76-85

• ACS 2018- “recommends that adults aged 45 years and older with average risk of colorectal cancer undergo regular screening” and continuing until age 75 with any of multiple screening strategies Individualize screening age 76-85

• State legislatures decide which guidelines insurers in their state must follow- Colorado is currently a USPSTF state

CRC Screening- Risk Groups• Increased risk- FDRs of patients with CRC or

Advanced Adenomas• Start at age 40 or earlier depending on # and age of

CRCs in family, colonoscopy is preferred • Hereditary Syndromes

• Start much earlier (12-25), annual colonoscopy

Family History of CRC Increases Risk

Fuchs et al NEJM 1994

PresenterPresentation NotesFamily history is a risk factor for colorectal cancer, and cancer tends to occur at an earlier age. On average, patients with a family member with a history of colorectal cancer develop cancer approximately 10 years earlier.

Familial and Hereditary CRC

Burt RW et al. Prevention and Early Detection of CRC, 1996

Sporadic(≈ 70%)

Familial (≈ 25%)

Lynch Syndrome (2-3%) (HNPCC)

Familial Adenomatous Polyposis (

Lynch Syndrome• Autosomal Dominant ≈ 1/300 – 3% of CRCs-• High CRC risk- up to 50%• Early onset- 44 yrs• Proximal location- 65%• Other cancers (Uterus, Ovary)• Under-recognized (

Familial Adenomatous Polyposis

Rare- 1/7,000 to 1/22,000 Autosomal Dominant High CRC risk ≈100% Easily recognized Genetic testing or

screening around age 12 Surveillance annually Attenuated FAP is

different

Colorectal Cancer- The Preventable Killer• Sequential progression from polyp to cancer• Common-

• 4th most common cancer in US and CO• Decreasing but increasing in the young

• Lethal• 2nd most common cause of cancer death in US/CO• Strongly dependent on stage at diagnosis

• Preventable• Prudent lifestyle changes• Screening is most effective prevention as well as early detection

strategy• Familial and Hereditary CRC require special attention

Slide Number 1Slide Number 2Slide Number 3Slide Number 4CRC is CommonCRC Incidence Over Time�The Good and BadCRC Risk Factors �Family History and CRC RiskCRC Risk Factors �Slide Number 10CRC StagingCRC is Preventable- Modifable Risk Factors�CRC Prevention�Risk Factors �Slide Number 15Slide Number 16Slide Number 17Slide Number 18Slide Number 19Slide Number 20Slide Number 21Lynch SyndromeFamilial Adenomatous PolyposisSlide Number 24Slide Number 25