when to start screening: exploring the issue of early
TRANSCRIPT
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
