Early diagnosis for and Prevention of Colorectal Cancer (CRC) and Polyps
We have a barrage of tests such as faecal occult blood(FOB), faecalDNA, flexible sigmoidoscopy, colonoscopy and virtual CT colonography (CTC) to address the possibility of significant colorectal neoplasia. Where do these tests fit and when should these be used individually or in combination? Before we can address this question, we need to understand the demographics of CRC.
Vast majority (65-85%) of CRC occur in people who have no family history and they are referred to as average risk category patients. Some 10-30% of CRC occur in patients who have a family history of CRC and they are referred to as moderate risk category. Remaining 5-6% of CRC occur in high risk patients such as those with non-polyposis colorectal cancer syndrome (HNPCC) and rarely in adenoma- tous polyposis coli or similar rare syndromes.
Over 4,400 patients die each year from CRC in Australia and some 1,000 lives can be saved by screening (1). CRC is the 3rd largest killer after heart disease and lung cancer. There are multiple studies now using either FOB or colonoscopy screening demonstrating early diagnosis and reduction of mortality from CRC.
Role of FOB: Multiple large overseas studies have demonstrated sensitivity of FOB of around 30% with reduction of mortality of between 15 –25% from CRC. The National Bowel Cancer Screening Pilot Program (2) in Australia, using immuno- chemical FOB, has demonstrated positive tests in 9% of 25,840 participants and a positive predictive value of 19% . Thus FOB (preferably immunochemical) should be carried out in asymptomatic average risk ( without family his- tory) subjects between the ages of 50-74.
Role of Faecal DNA: Faecal DNA has high sensitivity (52%) and specificity (94%) for CRC but works out more expensive than colonoscopy in the USA(3). Thus it is unlikely to be available or be used in Australia in the near future.
Role of Flexible Sigmoidoscopy: Original studies (4) recommended yearly FOB and 5 yearly flexible sigmoidoscopy for average risk patients and those moderate risk patients whose index relative had the CRC at an age equal to or older than 55.This is based on the presumption that 60-70% bowel cancers, which occur in the left side of the colon, would be within the reach of the flexible sigmoidoscope. I would favour a full colonoscopy which is just as easy to undertake, costs about the same yet views the whole bowel.
Role of Colonoscopy: While colonoscopy remains the gold standard for the inves- tigation of the symptomatic patient with bleeding or change in bowel habit, it is unlikely to be officially adopted as a screening tool for the average risk patient because of cost . However, some American literature are recommending 1st screening colonoscopy at 50 and then at 10 yearly interval. The American recommendation is based on studies using colonoscopy as the screening tool and concluded that, in over 50 year olds, the incidence of CRC could decrease by 58-86% and mortality could be reduced by 64-90%(5). In case of moderate risk patients with family history of CRC , yearly FOB with 5 yearly colonoscopy is al- most universally accepted. However, NHMRC guidelines in Australia recom- mends yearly FOB and 5 yearly colonoscopy only for those moderate risk patients whose first degree relative’s CRC was diagnosed below the age of 55. Two yearly and some cases (with germline mutation) yearly colonoscopies are required for high risk groups as in HNPCC.
CT (virtual) colonography (CTC): This tool is very unlikely to be a screening test with 20-40% false positive and false negative rates for polyps. One can not have polyps removed at CTC and is not likely to be cost effective for moderate risk patients if a subsequent colonoscopy is required for removal of polyps. CTC is clear- ly too expensive to be a screening tool for average risk patients compared to FOB. Radiation exposure and patient acceptability (staying awake through the entire procedure) are also additional issues. Some of these factors have recently led MBS to tighten the indications for the use of CTC.
Polyp surveillance: How often and for what types? For hyperplastic polyps, the colonoscopy should be repeated in 3-5 years if equal to or greater than 30 polyps were removed or multiple large polyps (equal to or greater than 1 cm) were removed from the ascending colon at the initial examination. Otherwise , hy- perplastic polyps do not require follow up colonoscopy.
Adenomas: If these were less than 1 cm in size, then colonoscopy should be repeat- ed in 5 years. If they were 1cm or larger, the colonoscopy should be repeated in 3 years. If numerous adenomas or sessile adenomas were found, then colonoscopy should be repeated in 1-2 years. On the other hand , if a large adenoma was re- moved piecemeal or there was high grade dysplasia, then repeat colonoscopy in 3-4 months and then at progressively longer intervals.
Prevention: NHMRC life style recommendations (6).
Diet: Men should consume less than 2,500 Kcals per day while women should consume less than 2,000 Kcals per day. Dietary fat should be less than 25%.Five portions of vegetables and fruits should be consumed every day. Intake of insolu- ble fibre such as wheat bran was recommended. Daily intake of calcium of 1000-1200mg is said to have a preventative ef- fect.
Life style: Regular physical exercise, reduction of alcohol intake and cessation of smoking were demonstrated to reduce risk for CRC.
Chemoprevention: While much was written about aspirin, NSAIDs and COX-2 inhibitors and their effect on reduction of polyp numbers and their sizes, prospective randomized trials on their role in the prevention of CRC are lacking and hence not recommended by NHMRC until further studies.
References;
1.Macrae F : Medicine Today 2004,5.
2.Dept of Health and Aging. Australia’s bowel cancer screening pilot and beyond . Final Report. at WWW.cancescreening.gov.au/bowel/pdfs/eval-oct05.pdf.
3.Imperiale TF et al NEJM 2004, 356, 2704-2714.
4.Winawer SJ et al Gastroenterology 2003,124,544-560.
5.Pignone M et al Ann. Internal Med 2002,137 :96-104.
6.NHMRC : Guidelines for the prevention, early detection and management of colorectal cancer. Commonwealth of Austral- ia. Canberra 2000.