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/ in 1982 to 72/ in 2009, women stable at 50/

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/ in 1982 to 16.2 / 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 : %- B : Penetrates wall : % C : Regional nodes : 40% D : Distant metastases : % 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 : % 70 Yrs : % 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 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: : : : : 400 1: : 300 1: 100 1: : 100 1: 50 1: : 65 1: 30 1: : 50 1: 25

RELATIVE RISK Average risk ( 75% have no family history ) Slight increased risk – 2 nd degree relative – 1.3 times Low Risk – 1 st degree relative ( eg parent ) with CRC older than 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 mg 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 million Australians eligible By 2017/18 biennial screening phased in between yrs Expect detect new cases /yr and save lives

FOBT Five randomised controlled trials of serial FOBT’s ( more than 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 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 %

Most positive FOBT’s will not be anything serious ! Do improve detection of asymptomatic CRC 65 – 90 % Dukes A/B compared to % control

FOBT PERFORMANCE 4 % +ve 3-5 % CRC % Adenomas % 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 % 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 % with no prospect for polyp removal nor biopsy

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 > 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 mSv > 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