Title: RECEDE Study: REducing Colonoscopies in patients without significant bowEl DiseasE
Funder: Department of Health and Social Care

Abstract: Investigating people with bowel symptoms uses a test that detects traces of blood in the stools, the FIT test. There are many possible reasons for positive tests. A few people have cancer. But most patients with symptoms don’t have any serious bowel disease, but have benign problems such as piles or irritable bowel syndrome (IBS). It is very difficult to diagnose on symptoms alone, those patients who have serious bowel disease and those who do not._x000D_ _x000D_ After a positive test, people are invited for colonoscopy – a sort of camera examination of the large bowel. Most people invited for colonoscopy don’t have cancer. Only about 5% of those with positive FIT tests have cancer. About 25% have other bowel diseases, but most (70%) have nothing seriously wrong at all. So, they have the inconvenience and discomfort of colonoscopy but don’t get any benefit from it._x000D_ _x000D_ We want to try adding another test, the VOC test, to see if we can separate those with positive FIT tests who do have something wrong, from those who don’t. The VOC test uses a urine sample. Using both tests might also be better for detecting cancer._x000D_ _x000D_ So, we think that using both tests might not only be better for detecting cancer, but also might mean that a lot of people will avoid having to have a colonoscopy._x000D_ _x000D_ _x000D_ We will recruit 1,819 patients with bowel symptoms from hospitals in different parts of England. They will provide stool samples for FIT and urine for VOC analysis. They will all have a colonoscopy to get a definite diagnosis. Then we will look at their FIT and VOC test results to see if in future, people with both tests negative don’t need colonoscopies.

Lay abstract: Research Question: Can the addition of urine volatile organic compounds (VOCs) to stool FIT testing rule out significant bowel disease (SBD) and by so doing, to reduce unnecessary invasive tests (colonoscopy) – right test for the right patient?_x000D_ _x000D_ Background: There is currently disparity between demand and available resources for colonoscopy. Around 300,000 patients are being referred annually suspected of colorectal cancer (CRC) and offered a colonoscopy. Only 30% will have significant bowel disease (SBD). SBD is defined as those with CRC, significant pre-malignant polyps (adenomas with size >10mm or with high grade dysplasia), inflammatory bowel disease or microscopic colitis. Of the remaining 70%, 40% are normal and 30% with benign conditions._x000D_ The National Institute for Health and Care Excellence (NICE) has recommended a stool test (faecal immunochemical testing for haemoglobin, known as FIT) in low risk groups suspected of CRC using a cut off of 10 µgHb/g faeces. When applied to high risk groups, FIT will miss CRC (~10%) and significant pre-cancerous polyps (~40%). A lower threshold might improve detection of SBD but it will not reduce the number of unnecessary colonoscopies. _x000D_ Consequently, we have been investigating a urine VOC (in addition to FIT) to improve detection of SBD. Urine VOCs analyses compounds that originate from the body and provides a chemical ‘fingerprint’ of health or disease state. In a preliminary study of 562 patients, stool FIT on its own detected 80% of those with CRC. However, the addition of urine chemical testing improved this to 97%. _x000D_ _x000D_ Aim: To investigate the diagnostic accuracy of stool FIT plus urine VOC compared to stool FIT alone to improve detection of SBD. _x000D_ _x000D_ Objectives:_x000D_ - Comparative sensitivity, specificity, positive predictive value (PPV) and negative predictive values (NPV) of (i) FIT, (ii) urine VOC and (iii) FIT plus urine VOC for detection of SBD _x000D_ - Potential reduction in number of colonoscopies_x000D_ - Quantifying quality-adjusted life years (QALYs) between those with FIT and VOC and FIT alone_x000D_ - Colonoscopy disutility _x000D_ _x000D_ Methods:_x000D_ RECEDE study will be a multicentre diagnostic accuracy study to recruit 1,819 patients referred for colonic investigations._x000D_ Inclusion criteria: Those referred with lower gastrointestinal symptoms through non-urgent & urgent pathways in accordance to NICE NG12 criteria for colonic examination. _x000D_ Exclusion criteria: Those who are pregnant, have CT colonography alone._x000D_ The intervention will be stool FIT and urine VOCs and the comparator will be colonoscopy (complete examination)._x000D_ _x000D_ Primary outcome will be sensitivity and specificity of stool FIT plus urine VOC compared to stool FIT alone in the detection of SBD._x000D_ _x000D_ Secondary outcome measures will include NPV and PPV as well as receiver operator characteristic of stool FIT plus urine VOC in detection of SBD. In addition to potential number of colonoscopies avoided in those without SBD, total NHS & Personal Social Services (PSS) costs and QALYs associated with each of the compared options will be calculated._x000D_ _x000D_ Anticipated impact and dissemination: Results will be presented at national and international gastrointestinal and oncology meetings and to Cancer Alliance groups as well as the Sustainability Transformation Programme board linked to NHS England.

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: CANCER AND NEOPLASMS