When to Start Screening: Exploring the Issue of Early

When to Start Screening: Exploring the Issue of Early-Onset

Colorectal Cancer

Robin B. Mendelsohn Department of Medicine, Gastroenterology and Nutrition Service

Memorial Sloan Kettering Cancer Center New York, New York, USA

This is not a new concept…

•37 patients < 40 from 1976-1997 •5,383 patients 20-40 from 1973-1999

•1025 patients ≤50 from 1976-2002 •SEER data 1992-2005 •in incidence of: 1.5%/year in men, 1.6%/year in women

• National Cancer Database – Hospital registry sponsored by

American College of Surgeons and American Cancer Society from 1998-2007

• 64,068 patients with young onset CRC, steady since 2001

• Nonwhite race/ethnicity

• Uninsured or Medicaid

• Distal colon/rectum

• Signet ring histologic subtype

• More advanced stages

You YN et al. Arch Int Med 2012

Top 5 Cancers: Ages 20-49

Lung (16%)

Colorectum (13%)

Brain (9%)

Leukemia (7%)

Pancreas (6%)

Breast (27%)

Lung (13%)

Colorectum (9%)

Cervix uteri (7%)

Ovary (5%)

Colorectum (11%)

Testis (9%)

Melanoma (8%)

Prostate (7%)

NHL (7%)

Breast (36%)

Thyroid (14%)

Melanoma (7%)

Colorectum (6%)

Cervix uteri (5%)

Men Women Men Women

Incidence Mortality

Among pts age <50 in 2016, estimated 14,200 new cases and 3,300 deaths

Striking differences in incidence trends

0

2

4

6

8

10

12

14

0

50

100

150

200

250

300

Inci

denc

e ra

te p

er 1

00,0

00

51% since 1994

Age ≥ 50 Age 20-49

Source: SEER 9 delay-adjusted rates, 1975-2012; Courtesy of Rebecca Siegel.

Men

Women

Men

Women

Trends by 10-year age groups

0

5

10

15

20

25

Inci

denc

e ra

te p

er 1

00,0

00 p

eopl

e

Age 40-49 1.9% annually since 1994

Age 30-39 2.2% annually since 1988

Age 20-29 3.8% annually since 1987

0

0.5

1

1.5

2

2.5

20-29 years

Source: SEER 9 delay-adjusted rates, 1975-2012; Courtesy of Rebecca Siegel. .

Taking a closer look at age-specific trends

0.1

1

10

100

1975-77 1980-82 1985-87 1990-92 1995-97 2000-02 2005-07 2010-12

Inci

denc

e pe

r 100

,000

60-64

50-54

45-49

40-44

35-39

30-34

25-29

20-24

55-59

Opposing trends between patients ages 50-54 and 55-59

0

10

20

30

40

50

60

70

80

Inci

den

ce r

ate

per

10

0,0

00

Colon

50-54

55-59

0

5

10

15

20

25

30

35

40

Rectum

+0.7% annually, 2003-2012

-2.7% annually, 2003-2012

-0.8% annually, 2003-2012

+2.4% annually, 2003-2012

55-59

50-54

Source: SEER 9 delay-adjusted rates, 1975-2012; Courtesy of Rebecca Siegel. .

Biggest in non-Hispanic whites

0

2

4

6

8

10

12

14

Non-Hispanicwhite

Colorectum

Colon

Rectum

0

2

4

6

8

10

12

14

Non-Hispanic black

0

2

4

6

8

10

12

14

Asian/Pacific Islander

0

2

4

6

8

10

12

14Hispanic

Colorectal Colon Rectum

NHW 2.4 1.8 3.3

Hispanic 2.2 1.9 2.6

API stable 0.6 stable

NHB stable stable 1.7

Annual % change from 1992-2012

0

2

4

6

1992-94 2010-12

Rectal cancer incidence rate

NHW Hispanic API NHB

Source: SEER 13 delay-adjusted rates, 1992-2012; ; Courtesy of Rebecca Siegel. .

2.6 in 1991

4.8 in 2012

Source: SEER 9 delay-adjusted rates, 1975-2012; ; Courtesy of Rebecca Siegel. .

Distal colon 2.1% annually since 1994

Rectum 2.7% annually since 1991

Proximal colon

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

1975-77 1980-82 1985-87 1990-92 1995-97 2000-02 2005-07 2010-12

Inci

denc

e ra

te p

er 1

00,0

00

Increase is in LEFT sided cancers

These are SIGNET-RING cell cancers

Mucinous

Signet-ring cell

Adenocarcinoma, NOS

Source: SEER 9 registries and Joinpoint Regression Program.

Younger patients are presenting at later stages

0

0.5

1

1.5

2

2.5

3

Colon

Localized

Regional

Distant

0

0.5

1

1.5

2

2.5

3

Rectum

Localized

Regional

Distant3.0% annually, 2003-2012

3.6% annually, 2003-2012

Source: SEER 9 delay-adjusted rates, 1975-2012; ; Courtesy of Rebecca Siegel. .

CRC Mortality Trends

0

0.5

1

1.5

2

2.5

3

3.5

4

4.5

5

1975 1980 1985 1990 1995 2000 2005 2010

De

ath

s p

er

10

0,0

00

20-49 years

0

20

40

60

80

100

120 50+

Source: National Center for Health Statistics, National Vital Statistics System.

Predictive Model shows incidence of young onset CRC will only continue to increase

Bailey CE et al. JAMA Surgery 2015.

Based on this, by 2030: •Incidence of CRC in young adults will nearly DOUBLE •10.9% of colon and 22.9% of rectal cancers will be in patients younger than screening guidelines •1 in 10 colon and nearly 1 in 4 rectal cancers will be diagnosed in those younger than 50!

This is clearly a MAJOR issue…

• But what are the mechanisms and molecular basis?

• The MAJOR issue of this MAJOR issue is that these trends do not always follow traditional risk factors….

CRC Risk Factors: Medical and Family History

Relative risk

Family history

1 first-degree relative 2.2

More than 1 relative 4.0

Relative with diagnosis before age 45

3.9

Medical history

Inflammatory bowel disease

Crohn disease 2.6

Ulcerative colitis

Colon 2.8

Rectum 1.9

Diabetes 1.2

These are SPORADIC cancers in an important percentage of patients

You YN et al. ASCRS Annual Meeting 2013.

Sporadic

Hereditary

Familial

Sporadic62%

Familial23%

Hereditary15%

CRC Risk Factors: Behavioral Increase risk: Relative risk Trend

Alcohol consumption (heavy vs. nondrinkers) 1.6

Obesity 1.2

Red meat consumption 1.2

Processed meat consumption 1.2 ?

Smoking (current vs. never) 1.2

Decrease risk: Relative risk Trend

Physical activity (colon) 0.7

Milk/total dairy consumption 0.8

Fruit consumption 0.9 ?

Vegetable consumption 0.9 ?

Total dietary fiber (10 g/day) 0.9 ?

Obesity and Diabetes Trends

6

16

0

5

10

15

20

19

80

19

83

19

86

19

89

19

92

19

95

19

98

20

01

20

04

20

07

20

10

Rat

e p

er

1,0

00

167%

Diabetes, ages 0-44 years

0

5

10

15

20

25

Per

cen

t

Ages 6-11

Ages 12-19

6%

Source: National Health and Nutrition Examination Survey. Source: National Health Interview Survey.

21%

Interesting obesity and CRC trends Obesity prevalence, ages 18-49, 2001 CRC incidence rates, ages 20-49, 2007-2011

Source: Behavioral and Risk Factors Surveillance System Source: US Cancer Statistics, WONDER Online Database

Environment may play a role

50+ years 20-49 years

Lifestyle and diet may play a role

0

2

4

6

8

10

12

14

2-18 yrs 19-39 yrs 2-18 yrs 19-39 yrs

Sweetened beverages Milk

Pe

rce

nt

of

tota

l dai

ly c

alo

rie

in

take

1977-78

1989-91

1994-96

1999-01

Nielsen et al. Am J Prev Med 2004.

Is the answer in the microbiome?

Ahn J et al. J Natl Cancer Inst. 2013.

Summary and Conclusions • CRC incidence rates in young adults continue to at a steady rate

• Left sided, later stages, many without family history of CRC

• ?Genetic ?Environmental ?Behavioral • More research clearly needed • Until then…awareness among clinicians and

young adults to facilitate earlier detection