28 June 2013

Bowel cancer screening – not the final solution. Prof Jonathan Rhodes, University of Liverpool Tuesday 2nd July 16.30 Hall 1A Screening reduces deaths from colorectal cancer by nearly one third [Atkin et al Lancet 2010] and is cost effective (less than £3,000 per QALY) [Tappenden et al, Gut 2007] so what’s not to like about it? The problem lies in the stats. Six per cent of the UK population get colorectal cancer and about 3% die from it at an average age of about 70 years thus losing around 10 years of life. A crude “back of envelope” calculation shows that if all deaths from colorectal cancer were completely abolished average life would be prolonged by about 3% of ten years which equals 3.6 months. More sophisticated modelling shows that flexible sigmoidoscopy done once at age 55 provides 13 additional “Quality adjusted life days” per person screened (adjusted for the actual 31% reduction in CRC mortality demonstrated in the Atkin Flex sig trial). Faecal occult blood screening at age 60 or over, as currently performed in England, prolongs life by an average 3.8 Quality adjusted life days – hardly a good selling point! Emotions often start to heighten when this argument is presented – “but what if you are one of the 6% destined to get CRC?” – but this is not an appropriate argument for a public health policy. What then is the alternative if we seek to prolong active life? (a legacy from watching dog-food commercials in my youth – ask a mature surgeon to explain). The short answer is that we should look at strategies that might reduce our risk, not only for getting colorectal cancer but also for succumbing to some of the commoner killers such as ischaemic heart disease, stroke and diabetes. These conditions in combination account for about 17 months of premature loss of life before age 75, compared with under 3 months for colorectal cancer [dhc.simcoe-york] . Avoidance of excessive calories, smoking, excess alcohol and taking regular exercise (plus, possibly, a daily aspirin) would likely reduce mortality very substantially from all of these conditions, including colorectal cancer, and have a vastly greater impact on duration of active life than screening for a single condition. If we are to look specifically at prevention of colorectal cancer then we need to get a clearer understanding of its pathogenesis. Doll and Peto estimated over 30 years ago that the huge geographical variation in colorectal cancer incidence implied that environmental factors, particularly diet, accounted for about 90% of its causation in western countries. Modern estimates might put this slightly lower eg around 80%. A huge amount of data shows associations between various dietary factors – high calorie, high meat, low vegetable intakes – but this does not prove causation. There is growing evidence that bacteria may play a crucial role, particularly in determining progression from dysplasia to cancer as a consequence of their interaction with the epithelium. In collaborative studies with the Jobin group in N Carolina we have recently shown that E. Coli that express the pks (polyketide synthase) gene island that produces a genotoxic metabolite (colibactin) are strongly associated with experimental colon cancer and with human sporadic colorectal cancer [Jobin et al Science 2012; Martin HM et al Gastro 2004]. Soluble plant fibres are able to block interaction between these bacteria and the epithelium [Roberts et al Gut 2010], a function we have termed “contrabiotic”, and this could account for some of the protective effects of soluble dietary fibre. We still need more research to be able to give a better answer to the question “Which five-a-day should I eat?”. In conclusion - screening for colorectal cancer does more good than harm but only has modest impact on overall survival. To prolong active life we need to look to interventions that simultaneously reduce risk for a range of commoner conditions as well as colorectal cancer. The general public need encouragement not only to participate in screening but also to adopt healthy life styles and not to rely on screening to bail them out after a lifetime of excess!

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