Long-term use of low-dose aspirin reduces the number of cases of colorectal cancer by a quarter, and the mortality caused by the disease by more than a third. These are the conclusions of an Article published Online First and in an upcoming Lancet. The study is by Professor Peter Rothwell, John Radcliffe Hospital, Oxford, and University of Oxford, UK, and colleagues.

Colorectal cancer is the second most common cancer in developed countries, with a lifetime risk of 5% and about 1 million new cases and 600,000 deaths worldwide each year. Most colorectal cancers develop from adenomas or 'polyps' and screening sigmoidoscopy and colonoscopy can reduce cancer risk by removal of these polyps. However screening is only partially effective, particularly for cancers of the proximal (upper) colon, which cannot be reached by sigmoidoscopy and are often missed on colonoscopy.

The same research group showed previously (Lancet 2007) that high-dose aspirin (≥500 mg daily) reduces long-term incidence of colorectal cancer, but adverse effects - such as increased bleeding - might limit its potential for long-term prevention. Also, the previous study was too small to look at effects on tumours in different parts of the colon and rectum. This new study by Rothwell and colleagues is the first to assess the long-term effectiveness of lower doses (75–300 mg daily) of aspirin on colorectal cancer incidence and mortality. They carried out a 20-year follow-up of five randomised trials.

The authors studied studied four randomised trials of aspirin, done originally in prevention of vascular disease, to determine effects of aspirin on colorectal cancer. In the four trials of aspirin versus placebo (mean duration of scheduled treatment six years), 391 (2·8%) of 14 033 patients had colorectal cancer during a median follow-up of 18·3 years. A pooled analysis of individual patient data showed that aspirin reduced the 20-year risk of colon cancer by 24% and mortality from colon cancer by 35%. Results were consistent across trials, with no increase in benefit at doses of aspirin greater than 75 mg daily. The data also showed a reduction in the 20-year absolute risk of any fatal colorectal cancer after 5 years' treatment with 75—300mg aspirin daily, from about 3.5% to 1.5%

The authors found that reductions in incidence and death due to colorectal cancer were made up almost entirely of reductions in risk of proximal colon cancer of about 70%, but had no effect on distal colon cancer and only a small effect on rectal cancer. Work also published in The Lancet and colleagues by Wendy Atkin and colleagues (April 2010) showed that a one-off sigmoidoscopy reduced colorectal cancer mortality by 43% in those screened and incidence by one third.

The authors believe this new study could help push the recently finely balanced risk-benefit debate regarding long-term aspirin use back towards favouring benefit. They conclude: "The five trials we studied all predated endoscopic screening for adenomas, which also reduces colorectal cancer incidence and mortality, and might therefore reduce the absolute benefit of aspirin. However, the suggestion of a particular effect of aspirin on more aggressive and rapidly growing tumours might allow less frequent screening, and the prevention of proximal colonic cancers by aspirin, which would not be identified by sigmoidoscopy, is clearly important. It is therefore probable that these two approaches to prevention of colorectal cancer will be synergistic."

Professor Rothwell says: "Our findings suggest that long-term low-dose aspirin treatment and sigmoidoscopy screening would combine to substantially reduce cancer incidence in all parts of the colon and rectum."

He also notes the recent announcement of the UK government (during the Conservative Party Conference) to launch a nationwide sigmoidoscopy screening programme, that followed on from the publication of Atkin and colleagues. Professor Rothwell adds: "The new findings on the effect of low-dose aspirin should be included in advice given to the public on the screening programme and other approaches to preventing colorectal cancer."

In a linked Comment, Dr Robert Benamouzig and Dr Bernard Uzzan, Avicenne Hospital, Bobigny, France, say: "This interesting study would incite clinicians to turn to primary prevention of colorectal cancer by aspirin at least in high risk-populations. Specific guidelines for aspirin chemoprevention would be the next logical step. "

Source: The Lancet