COLORECTAL CANCER

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COLORECTAL CANCER

• STATISTICS
• RISK ASSESSMENT
• SCREENING OPTIONS
  
  
  Luke Crantock

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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

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• Rare before the age of 50 ( 7.6 of all CRCs )
  
• 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.

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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

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Number of deaths from commonly occurring cancers
In Australia 2010
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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

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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

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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 )

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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

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• 1990 Fearon Vogelstein proposed multistep
  hypothesis for tumorigenesis particularly p53 and
  APC genes involved

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RISKS - CRC

• 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

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CRC risk -median age Dx 70

• At 5 yrs 10 yrs 20
  yrs
• 30 1 7000 1 2000 1 350
  
• 40 1 1200 1 400 1 90
  
• 50 1 300 1 100 1 30
  
• 60 1 100 1 50 1
  20
• 70 1 65 1 30
  1 15
• 80 1 50 1 25

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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

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• 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

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Medical History

• Past Hx Polyps
• Past Hx CRC
• Hx IBD

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Lifestyle factors-Prevention

• Healthy Lifestyle Physical activity
• Healthy BMI
  
• Limit alcohol
• Quit smoking

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Lifestyle Diet,

• Regular activity 30-60min/day
• NHMRC attributes dietary factors to 50 CRC
• Reduce daily energy intake lt 2000 calories/day
  for men, lt 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 lt2 std drinks/day

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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

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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

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One third of CRC cases could be prevented by
screening !
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Survival depends on early detection !
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SCREENING -Screening involves asymptomatic
patients !

• Faecal Occult Blood Testing
• Flexible Sigmoidoscopy
• Colonoscopy
• Barium Enema
• Virtual Colonoscopy
• Detection of DNA mutations stool tumour markers

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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

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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

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FOBT

• Five randomised controlled trials of serial
  FOBTs ( more than 250 000 subjects ) -
  Reduction in CRC mortality of 33 with annual
  screening
• 21 reduction with biennial screening

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FOBT - Types Available

• Guaiac Hemoccult
• Haem-derived porphyrin HemoQuant
• Faecal Immunochemical tests Inform , HemeSelect

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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

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Immunochemical Tests - FIT

• Detection is based on antibodies specific for
  human Hb
• Not subject to interference by diet or drugs
• FITs are selective for colorectal bleeding as
  Hb is degraded by digestion ( do not detect
  gastric bleeding )
• More sensitive than Guaiac FOBT s with similar
  specificity 0.1mg Hb per gram faeces . FITs
  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

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Most positive FOBTs will not be anything serious
!

• Do improve detection of asymptomatic CRC
• 65 90 Dukes A/B compared to 33-35
  control

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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

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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

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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

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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

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Virtual Colonoscopy

• CT or MRI imaging used to develop 2 and 3
  dimensional images of colon
• Colonic preparation and bowel insufflation with
  CO2
• No sedation
• Minimal risk of bowel perforation , infection or
  bleeding
• Sensitivity good for polyps gt 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

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Radiation Exposure

• Millisieverts
• 2-3 mSv/yr
• CT 5- 15mSv
• CXR - 0.02mSv
• gt 100mSv may increase cancer risk
• gt1000 mSv cumulative increase cancer risk in
  later years 5/100 develop cancer

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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

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Key Points

• Lifestyle Measures
• Identify risk
• Screening for asymptomatic patients
• 33 reduction in mortality with early detection

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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

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Hang in there