Establishing the added benefit of measuring MMP9 in FOB positive patients as a part of the Wolverhampton colorectal cancer screening programme

<p>Abstract</p> <p>Background</p> <p>Bowel cancer is common and a major cause of death. The NHS is currently rolling out a national bowel cancer screening programme that aims to cover the entire population by 2010. The programme will be based on the Faecal Occult Blood test (FOBt) that reduces mortality from colon cancer by 16%. However, FOB testing has a relatively low positive predictive value, with associated unnecessary cost, risk and anxiety from subsequent investigation, and is unacceptable to a proportion of the target population. Increased levels of an enzyme called matrix metalloproteinase 9 (MMP9) have been found to be associated with colorectal cancer, and this can be measured from a blood sample. MMP9 has potential for detecting those at risk of having colorectal cancer. The aim of this study is to assess whether MMP9 estimation enhances the predictive value of a positive FOBt.</p> <p>Methods and design</p> <p>FOBt positive people aged 60–69 years attending the Wolverhampton NHS Bowel Cancer Screening Unit and providing consent for colonoscopy will be recruited. Participants will provide a blood sample prior to colonoscopy and permission for collection of the clinical outcome from screening unit records. Multivariate logistic regression analyses will determine the independent factors (patient and disease related, MMP9) associated with the prediction of neoplasia.</p> <p>Discussion</p> <p>Colorectal cancer is a major cause of morbidity and mortality. Pilot studies have confirmed the feasibility of the national cancer screening programme that is based on FOBt. However, the test has high false positive rates. MMP9 has significant potential as a marker for both adenomas and cancers. This study is to examine whether using MMP9 as an adjunct to FOBt improves the accuracy of screening and reduces the number of false positive tests that cause anxiety and require invasive and potentially harmful investigation.</p

Elevated serum matrix metalloproteinase 9 (MMP-9) concentration predicts the presence of colorectal neoplasia in symptomatic patients

Early detection of polyps or colorectal carcinoma can reduce colorectal carcinoma-associated deaths. Previous studies have demonstrated raised serum levels of matrix metalloproteinase 9 (sMMP-9) in a range of cancers. The aim of this study was to investigate the role of sMMP-9 levels in identifying colorectal neoplasia. Consenting patients donated a blood sample and were assessed by proforma-led history and physical examination. Samples were analysed for sMMP-9 concentration (enzyme-linked immuno-sorbant assay) and compared to final diagnoses. Logistic regression modelling determined independent factors associated with neoplasia. A total of 365 patients were recruited of whom 300 were analysed, including 46 normal controls. A total of 27 significant adenomas and 63 malignancies were identified. The median sMMP-9 concentration was 443ng ml−1 (IQR: 219–782; mean: 546). Patients with neoplasia had significantly elevated sMMP-9 levels (P<0.001). Logistic regression modelling identified elevated log(sMMP-9) as the most significant predictor of neoplasia (χ2=38.33, P<0.001). Other significant factors were age, sex, smoking history, abdominal pain and weight loss. The model accurately predicted neoplasia in 77.3% of cases. Sensitivity and specificity were 77.9 and 77.1%. sMMP-9 estimation can accurately stratify patient to low- or high-risk cohorts. Serum sampling is a potential means of avoiding unnecessary colonoscopy and reducing patient anxiety, iatrogenic morbidity and mortality, and cost

Population screening for colorectal cancer: the implications of an ageing population

Population screening for colorectal cancer (CRC) has recently commenced in the United Kingdom supported by the evidence of a number of randomised trials and pilot studies. Certain factors are known to influence screening cost-effectiveness (e.g. compliance), but it remains unclear whether an ageing population (i.e. demographic change) might also have an effect. The aim of this study was to simulate a population-based screening setting using a Markov model and assess the effect of increasing life expectancy on CRC screening cost-effectiveness. A Markov model was constructed that aimed, using a cohort simulation, to estimate the cost-effectiveness of CRC screening in an England and Wales population for two timescales: 2003 (early cohort) and 2033 (late cohort). Four model outcomes were calculated; screened and non-screened cohorts in 2003 and 2033. The screened cohort of men and women aged 60 years were offered biennial unhydrated faecal occult blood testing until the age of 69 years. Life expectancy was assumed to increase by 2.5 years per decade. There were 407 552 fewer people entering the model in the 2033 model due to a lower birth cohort, and population screening saw 30 345 fewer CRC-related deaths over the 50 years of the model. Screening the 2033 cohort cost £96 million with cost savings of £43 million in terms of detection and treatment and £28 million in palliative care costs. After 30 years of follow-up, the cost per life year saved was £1544. An identical screening programme in an early cohort (2003) saw a cost per life year saved of £1651. Population screening for CRC is costly but enables cost savings in certain areas and a considerable reduction in mortality from CRC. This Markov simulation suggests that the cost-effectiveness of population screening for CRC in the United Kingdom may actually be improved by rising life expectancies