Transcript COLORECTAL CANCER - Oncology Clinics Victoria

COLORECTAL CANCER
 STATISTICS
 RISK ASSESSMENT
 SCREENING OPTIONS
Luke Crantock
How Common is Bowel Cancer ?
 14,410 new cases diagnosed in 2010
 More common in Men
1 : 17 M, 1 : 26 F
 7982 ( M), 6428 (F ) – 12.6% all new cancers
 Rare before the age of 50 ( 7.6 % of all CRC’s )
 Risk at 85 is 1 : 12
 Incidence - increased in men from 66.7/10 000 in
1982 to 72/100 000 in 2009 , women stable at
50/100 000.
MORTALITY
 Second most common cancer death : 14% ( Lung 20% )
 2010 : 3982 deaths from CRC
 80 Australians dying from cancer /week – one death
every 2 hours
 Mortality rate has decreased from 31.5/100 000 in 1982
to 16.2 /100 000 in 2010
 Risk dying from cancer at age 85 is 1: 45
Number of deaths from commonly occurring
cancers In Australia 2010
5 YEAR SURVIVAL ACPS, pTNM
 A : Localised within bowel : 80-90 % B : Penetrates wall : 55-80 %
 C : Regional nodes : 40%
 D : Distant metastases : 8 -10 %
 Early detection is essential, survival relatively good
compared to other cancers such as stomach, lung
pancreas etc
 Fewer than 40 % cancers are detected early
Aetiology
 Interaction between inherited susceptibility and
environmental factors leading to accumulation of
mutations in DNA resulting in uncontrolled cell
growth
 Benign precursor lesion – Adenoma
 Sequential multistep process involving damage to
genes leads to invasive malignancy
How Common are Polyps ?
 50 Yrs : 30%
 60 yrs : 40-50 %
 70 Yrs : 50-65 %
 Risk family history Adenoma similar to CRC
 Serrated adenoma ( Methylation )
All in the Genes
 Gene changes may be acquired ( diet, age etc ) or
inherited.
 Tumours suppressor genes ( protective )
- acquired or inherited
 DNA repair genes - acquired or inherited
 Oncogenes – activation of ( K-ras ) - acquired
 1990 Fearon & Vogelstein proposed multistep
hypothesis for tumorigenesis particularly p53 and APC
genes involved
RISKS - CRC
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Age
( low before 50yrs -7.6 %)
Family History
Medical History ( polyps , IBD )
Environmental Factors
Up to 75 % of CRC could be prevented by
improvements in diet , activity and screening
CRC risk -median age Dx 70
 At
5 yrs
10 yrs
20 yrs
 30
1: 7000
1: 1200
1: 300
1: 100
1: 65
1: 50
1: 2000
1: 400
1: 100
1: 50
1: 30
1: 25
1: 350
1: 90
1: 30
1: 20
1: 15
 40
 50
 60
 70
 80
RELATIVE RISK
 Average risk ( 75% have no family history )
 Slight increased risk – 2nd degree relative – 1.3 times
 Low Risk – 1st degree relative ( eg parent ) with CRC
older than 55 - 2 times risk
 Moderate Risk- One relative less than 55 yrs or Father
and grandfather , (one younger than 50 risk) 3-6 times
 High Risk – FAP, HNPCC syndromes, “3,2,1 “ rule – 3
relatives ( one first degree ), 2 generations , one less
than 50yrs. 80% risk of CRC, 40-60% endometrial or
ovarian cancer
Medical History
 Past Hx Polyps
 Past Hx CRC
 Hx IBD
Lifestyle factors-Prevention
 Healthy Lifestyle – Physical activity
– Healthy BMI
– Limit alcohol
– Quit smoking
Lifestyle & Diet,
 Regular activity 30-60min/day
 NHMRC attributes dietary factors to 50% CRC
 Reduce daily energy intake < 2000 calories/day for
men, < 2000 calories /day for women.
 Increased risk Type 2 Diabetes
 Reduces fats - Exception is omega-3 fatty acids inverse
correlate –reduce epithelial proliferation
 Limit alcohol <2 std drinks/day
Lifestyle & Diet
 5 or more serves vegetables/day
 2 serves fruit/day
 Encourage cereals
 Lean meats, avoid charring & processed meats
 Stop smoking ( 50% increased risk )
 Folate, Selenium
 Aspirin, NSAIDS
 HMG-Co A reductase inhibitors
 1000-1200mg calcium/day
Patient Assessment
 Any family members with CRC ? ( 75 % do not )
 Any family members with polyps ?
 Any previous polyps ?
 Any rectal bleeding ?
 Any recent change in bowel habit ?
 Any new abdominal pain or weight loss ?
 A history of colitis ?
 Iron deficiency ? – up to 15 % have CRC
One third of CRC cases could
be prevented by screening !
Survival depends on early
detection !
SCREENING -Screening involves asymptomatic
patients !
 Faecal Occult Blood Testing
 Flexible Sigmoidoscopy
 Colonoscopy
 Barium Enema
 Virtual Colonoscopy
 Detection of DNA mutations & stool tumour
markers
Screening
 One step – Colonoscopy , select on age.
Many individuals will have –ve test
( 4-7 % develop CRC in life time )
Expense and morbidity .
Are risks matched by benefit ?
 Two Step – Screen with cheap test such as
FOBT follow by colonoscopy if +ve
- evidence based
- colonoscopic resources managed
- overcomes initial patient reluctance
for invasive test
NBCSP
 Pilot from 2002
 About 45% participation rate
 Now testing 50, 55, 60 and 65 yr olds
 By 2015 include 70 yr olds
 2012-2015 4.8 million Australians eligible
 By 2017/18 biennial screening phased in between 50-
74 yrs
 Expect detect 12 000 new cases /yr and save 300-500
lives
FOBT
 Five randomised controlled trials of serial FOBT’s
( more than 250 000 subjects ) - Reduction in CRC
mortality of 33 % with annual screening
 21% reduction with biennial screening
FOBT - Types Available
 Guaiac – Hemoccult
 Haem-derived porphyrin – HemoQuant
 Faecal Immunochemical tests – Inform , HemeSelect
Guaiac Tests
 Dependent on peroxidase activity of heme
molecule which is stable during digestion and
therefore not selective for colorectal bleeding
 Restriction of heme rich or peroxidase rich foods
and some medications . Vit C gives false negatives
 Requires testing on three separate occasions
 Not suitable for automated testing
Immunochemical Tests - FIT
 Detection is based on antibodies specific for human Hb
 Not subject to interference by diet or drugs
 FIT’s are selective for colorectal bleeding as Hb is degraded
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by digestion ( do not detect gastric bleeding )
More sensitive than Guaiac FOBT ‘s with similar specificity
: 0.1mg Hb per gram faeces . FIT’s have better performance
than guaiac tests
Sampling of toilet bowl water around immersed stool –
improved participation
Mass processing by automated reading
FIT tests can be quantified. Sensitivity for cancer may be as
high as 68-85 %
Most positive FOBT’s will not be anything serious !
 Do improve detection of asymptomatic CRC
 65 – 90 % Dukes A/B compared to 33-35 % control
FOBT PERFORMANCE
 4 % +ve
 3-5 % CRC
 30 - 45 % Adenomas
 30-40 % CRC missed.
 Over 13 yrs – Annual screening : 33% reduction in
mortality
-Biennial : 20 % reduction
Flexible Sigmoidoscopy
 Visualisation of distal bowel where 70 % of cancers
occur ( rectum 40% and sigmoid )
 No sedation
 Retrospective case controlled studies support
reduction in mortality for distal cancers ( 70 % )
but not for proximal lesions
 A distal adenoma indicates 2-5 % chance of
advanced proximal adenoma
 If sigmoidoscopy negative – repeat in 5 yrs
COLONOSCOPY
 No RCTs but National Cooperative Polyp Study cohort-1418
pts, 1 or more adenomas removed , followed progressively,
CRC incidence 76-90 % lower than expected.
Other estimates at least 50 % reduction in risk.
 Missed polyps 6-25 %, 6-10 min withdrawal time, good
prep
 Cost benefit analysis suggests value for colonoscopy at 10
yearly intervals – US guidelines
 1 : 500 post polypectomy haemorrhage
 1 : 1500 chance of bowel perforation
Double Contrast Barium Enema
 No randomised trials showing reduction in mortality
 Inferior sensitivity to colonoscopy by 5 - 10 % with no
prospect for polyp removal nor biopsy
Virtual Colonoscopy
 CT or MRI imaging used to develop 2 and 3 dimensional
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images of colon
Colonic preparation and bowel insufflation with CO2
No sedation
Minimal risk of bowel perforation , infection or bleeding
Sensitivity good for polyps > 10 mm
No chance of biopsy or polyp removal
No texture or colour detail
High colonoscopy follow up rates – 15 – 25 %
Radiation exposure
No randomised trials showing benefit
Radiation Exposure
 Millisieverts
 2-3 mSv/yr
 CT – 5- 15mSv
 CXR - 0.02mSv
 > 100mSv may increase cancer risk
 >1000 mSv cumulative increase cancer risk in later
years 5/100 develop cancer
Detection of DNA mutations and tumour
markers in stool
 Mutations of genes are associated with
malignancy and adenomas
 Oncogenes ( RAS ) , tumour suppressor genes
( p53 & APC ) , microsatellite instability
sequences are known and can be assessed
 Cells from tumours with the above mutations are
shed into the gut and can be detected in stool
 Screening for a panel of markers is suggested
combined with FOBT – promise for future
Key Points
 Lifestyle Measures
 Identify risk
 Screening for asymptomatic patients
 33% reduction in mortality with early detection
Practical approach to screening – see NHMRC
clinical guidelines
 Thorough history and physical exam
 Discussion of diet and lifestyle – boost fruit and
vegetable intake ,allow lean meat (not charred ),
no real benefit from antioxidants or vitamin
supplements ( folate )
 Average risk - FOBT second yearly +/- endoscopy 5
yearly
 Above average risk ( 5 -8 % ) – 5 yearly colonoscopy
with interval FOBT
 High Risk – special consideration and referral
Hang in there