Cancer Risk with IBD

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About Crohn's Disease

About Ulcerative Colitis

An Article written for the CCSG by Dr Alan Fraser (Senior Lecturer, University of Auckland).

Inflammatory bowel disease can significantly affect quality of life but it is rare to have a life-threatening complication of the disease with modern management. However the threat of cancer is a question that looms high in the minds of many patients. From the physician's point of view the issue tends to be of secondary concern with most attention given to the appropriate treatment of disease activity. All patients with inflammatory bowel disease need to have some understanding of this issue even if only to avoid unnecessary anxiety.

What are the issues if you have inflammatory bowel disease?

There are two main questions. Firstly, what is my risk of colon cancer and what can be done to reduce the risk? Secondly, do any of the medications (in particular azathioprine) have any long-term risks?

It is accepted that there is an increased risk of colon cancer with ulcerative colitis that has been active for at least 10 years and where the disease involves at least half of the colon. What is difficult is to estimate is the degree of risk. From point of view of most practising gastroenterologists today it seems exceptionally rare to have a death from colon cancer that has arisen in a patient with ulcerative colitis. However the published literature needs to be carefully considered.

There are several confounding problems when looking at the literature. There are widely differing reported risks from different countries . In fact, two studies, one from Denmark and one from Israel have suggested that the rate of colorectal cancer for their clinic population was no different from the general population. Unfortunately no data are available from New Zealand. Another confounding factor is that the risk of colorectal cancer in ulcerative colitis may be decreasing over the decades. The reasons for this observation are unclear. There is good evidence emerging that maintenance treatment with 5-ASA compounds (that is Salazopyrin, Pentasa, Asacol, Dipentum) decreases the risk of colorectal cancer. Regular clinic follow-up is also associated with decreased risk and having even just one colonoscopy is enough to give a decreased risk (I will come to the issue of regular or surveillance colonoscopy later).

I have recently returned from a sabbatical year in Oxford, United Kingdom, an acknowledged centre of excellence for inflammatory bowel disease for at least 40 years. It was at Oxford that the first trials of steroid treatment for ulcerative colitis were performed and the protocols that were developed are still followed throughout the world. As part of my research I reviewed the entire records of the IBD clinic &endash; some 2205 clinical notes. Overall I found 23 cases of colorectal cancer. This was definitely an excess over a predicted number of approximately 5 cases. However the absolute risk is small and the majority of these colorectal cancers were detected early and could be treated by surgery. To put this into perspective another 61 cancers of varying types were also diagnosed in this clinic population over a 30 year period. The risk of other cancers is not increased with IBD but is the same as the general population. Reducing the risk of colon cancer to that of the general population still does not eliminate the risk of cancer in general. Of course, cancer overall causes only 1/3 of deaths in our country. Heart disease remains the number one cause of death whether we have IBD or not!

In the Oxford study, there was the expected increase in risk of colorectal cancer with increasing years of follow-up with ulcerative colitis. There were no cases in patients with the disease involving just the rectum or sigmoid colon. After 10 years of ulcerative colitis, the risk was 0.5%, after 20 years 1.3%, after 30 years 2.4% and 40 years 7.6%. These figures are at the low range of what has been reported but are likely to be similar to the current New Zealand situation.

Table 1. Increased colorectal cancer risk associated with ulcerative colitis (UC) compared with the general population.

Years with UC	Risk
10	0.5%
20	1.3%
30	2.4%
40	7.6%

Many studies have shown that regular colonoscopies are effective in detecting early colon cancers or the changes that predict an increased risk of colorectal cancer (dysplasia). The reality is that it is difficult to run a comprehensive screening program. All studies have shown that more cancers are diagnosed outside of the screening programme and less than half of patients stay in a regular surveillance programme (for whatever reasons). The frequency of screening procedures required to reduce the risk of colorectal cancer is debated. Shorter intervals between procedures may be better but public funding of health requires strong evidence for cost-effectiveness. A reasonable compromise is 3-yearly colonoscopy after 10 years of ulcerative colitis. The risk of cancer is often introduced into the discussion when surgery (colectomy) is being considered. My interpretation of the data is that the risk of developing colorectal cancer is only a small part of decision to proceed to surgery for most patients. The main issue regards the current quality of life and what improvement could be expected after surgery

There may be an increased risk of colon cancer with colonic Crohn's disease. This is very small (many studies have not shown any difference from the risk for the general population) and regular surveillance has not been the policy for most gastroenterology departments.

What are the main messages?

Regular clinic attendance and discussion of individual risks with your physician is sensible. The use of maintenance long-term 5-ASA drugs does appear to have some protective effects.

The second issue is the long-term risks from medication, in particular azathioprine. The long-term problems with prednisone (steroids) are well known (oesteporosis, thinning of skin, hypertension, diabetes, weight gain and fluid retention). There has been a trend towards greater use of azathioprine over recent years. Most gastroenterologists are very impressed with the sustained remissions that are achieved with this medication for both ulcerative colitis and Crohn's disease. Azathioprine does not have the troublesome side-effects that I have described for long-term steroids. Relapse does occur over time after stopping azathioprine. The question therefore is how long to continue treatment once remission has been achieved. The anxiety in some physicians' minds has been data from renal transplant patients who do have a small but definite increased risk of skin tumours and perhaps lymphomas after 10-15 years of azathioprine treatment. The situation for renal transplant patients is very much more complex than for patients with IBD, yet the question remains. Only one published study (from St Marks, London) has given some long term data for IBD patients. This showed no increased risk. I have also looked at this question in the Oxford clinic and similarly found no increased risk of cancer.

It is not possible to give a 100% guarantee because this sort of reassurance requires data from many long-term studies - this information is just not available! I feel the current data allows us to treat with azathioprine with confidence for at least 5 years if the clinical need is there. Many patients have been treated for 10-15 years without any problems.

All treatments have risks and benefits. Your physician tries to weight this up on your behalf. Your informed involvement in these discussions is a big help for making the right choices for your treatment.

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