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 CRC80 Australians dying from cancer /week – one

death every 2 hoursMortality rate has decreased from 31.5/100

000 in 1982 to 16.2 /100 000 in 2010Risk dying from cancer at age 85 is 1: 45

Number of deaths from commonly occurring cancers In Australia 2010

5 YEAR SURVIVAL ACPS, pTNMA : 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

AetiologyInteraction 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 CRCSerrated adenoma ( Methylation )

All in the GenesGene 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

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: 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

RELATIVE RISKAverage 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 PolypsPast Hx CRCHx IBD

Lifestyle factors-Prevention

Healthy Lifestyle – Physical activity – Healthy BMI

– Limit alcohol – Quit smoking

Lifestyle & Diet, Regular activity 30-60min/dayNHMRC attributes dietary factors to 50%

CRCReduce daily energy intake < 2000

calories/day for men, < 2000 calories /day for women.

Increased risk Type 2 DiabetesReduces 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/day2 serves fruit/dayEncourage cerealsLean meats, avoid charring & processed

meats Stop smoking ( 50% increased risk )Folate, SeleniumAspirin, NSAIDSHMG-Co A reductase inhibitors1000-1200mg calcium/day

Patient AssessmentAny 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 TestingFlexible SigmoidoscopyColonoscopyBarium EnemaVirtual ColonoscopyDetection of DNA mutations & stool

tumour markers

ScreeningOne 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

NBCSPPilot from 2002About 45% participation rateNow testing 50, 55, 60 and 65 yr oldsBy 2015 include 70 yr olds2012-2015 4.8 million Australians eligibleBy 2017/18 biennial screening phased in

between 50-74 yrsExpect detect 12 000 new cases /yr and save

300-500 lives

FOBTFive 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 AvailableGuaiac – HemoccultHaem-derived porphyrin – HemoQuantFaecal Immunochemical tests – Inform ,

HemeSelect

Guaiac TestsDependent 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 - FITDetection is based on antibodies specific for human

Hb Not subject to interference by diet or drugsFIT’s 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 . FIT’s have better performance than guaiac tests

Sampling of toilet bowl water around immersed stool – improved participation

Mass processing by automated readingFIT 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 % +ve3-5 % CRC30 - 45 % Adenomas 30-40 % CRC missed.Over 13 yrs – Annual screening : 33%

reduction in mortality -Biennial : 20 % reduction

Flexible SigmoidoscopyVisualisation of distal bowel where 70 % of

cancers occur ( rectum 40% and sigmoid )No sedationRetrospective 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

COLONOSCOPYNo 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 haemorrhage1 : 1500 chance of bowel perforation

Double Contrast Barium EnemaNo randomised trials showing reduction in

mortalityInferior sensitivity to colonoscopy by 5 - 10 %

with no prospect for polyp removal nor biopsy

Virtual ColonoscopyCT or MRI imaging used to develop 2 and 3

dimensional images of colonColonic preparation and bowel insufflation with CO2No sedationMinimal risk of bowel perforation , infection or

bleedingSensitivity good for polyps > 10 mmNo chance of biopsy or polyp removal No texture or colour detailHigh colonoscopy follow up rates – 15 – 25 %Radiation exposureNo randomised trials showing benefit

Radiation ExposureMillisieverts2-3 mSv/yrCT – 5- 15mSvCXR - 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 MeasuresIdentify riskScreening for asymptomatic patients33% reduction in mortality with early

detection

Practical approach to screening – see NHMRC clinical guidelines

Thorough history and physical examDiscussion 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