Is whole-colon investigation by colonoscopy, computerised tomography colonography or barium enema necessary for all patients with colorectal cancer symptoms, and for which patients would flexible sigmoidoscopy suffice? A retrospective cohort study.

BACKGROUND: For patients referred to hospital with suspected colorectal cancer (CRC), it is current standard clinical practice to conduct an examination of the whole colon and rectum. However, studies have shown that an examination of the distal colorectum using flexible sigmoidoscopy (FS) can be a safe and clinically effective investigation for some patients. These findings require validation in a multicentre study. OBJECTIVES: To investigate the links between patient symptoms at presentation and CRC risk by subsite, and to provide evidence of whether or not FS is an effective alternative to whole-colon investigation (WCI) in patients whose symptoms do not suggest proximal or obstructive disease. DESIGN: A multicentre retrospective study using data collected prospectively from two randomised controlled trials. Additional data were collected from trial diagnostic procedure reports and hospital records. CRC diagnoses within 3 years of referral were sourced from hospital records and national cancer registries via the Health and Social Care Information Centre. SETTING: Participants were recruited to the two randomised controlled trials from 21 NHS hospitals in England between 2004 and 2007. PARTICIPANTS: Men and women aged ≥ 55 years referred to secondary care for the investigation of symptoms suggestive of CRC. MAIN OUTCOME MEASURE: Diagnostic yield of CRC at distal (to the splenic flexure) and proximal subsites by symptoms/clinical signs at presentation. RESULTS: The data set for analysis comprised 7380 patients, of whom 59% were women (median age 69 years, interquartile range 62-76 years). Change in bowel habit (CIBH) was the most frequently presenting symptom (73%), followed by rectal bleeding (38%) and abdominal pain (29%); 26% of patients had anaemia. CRC was diagnosed in 551 patients (7.5%): 424 (77%) patients with distal CRC, 122 (22%) patients with cancer proximal to the descending colon and five patients with both proximal and distal CRC. Proximal cancer was diagnosed in 96 out of 2021 (4.8%) patients with anaemia and/or an abdominal mass. The yield of proximal cancer in patients without anaemia or an abdominal mass who presented with rectal bleeding with or without a CIBH or with a CIBH to looser and/or more frequent stools as a single symptom was low (0.5%). These low-risk groups for proximal cancer accounted for 41% (3032/7380) of the cohort; only three proximal cancers were diagnosed in 814 low-risk patients examined by FS (diagnostic yield 0.4%). LIMITATIONS: A limitation to this study is that changes to practice since the trial ended, such as new referral guidelines and improvements in endoscopy quality, potentially weaken the generalisability of our findings. CONCLUSIONS: Symptom profiles can be used to determine whether or not WCI is necessary. Most proximal cancers were diagnosed in patients who presented with anaemia and/or an abdominal mass. In patients without anaemia or an abdominal mass, proximal cancer diagnoses were rare in those with rectal bleeding with or without a CIBH or with a CIBH to looser and/or more frequent stools as a single symptom. FS alone should be a safe and clinically effective investigation in these patients. A cost-effectiveness analysis of symptom-based tailoring of diagnostic investigations for CRC is recommended. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95152621. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 66. See the NIHR Journals Library website for further project information.

Computed tomographic colonography compared with colonoscopy or barium enema for diagnosis of colorectal cancer in older symptomatic patients: two multicentre randomised trials with economic evaluation (the SIGGAR trials).

BACKGROUND: Computed tomographic colonography (CTC) is a relatively new diagnostic test that may be superior to existing alternatives to investigate the large bowel. OBJECTIVES: To compare the diagnostic efficacy, acceptability, safety and cost-effectiveness of CTC with barium enema (BE) or colonoscopy. DESIGN: Parallel randomised trials: BE compared with CTC and colonoscopy compared with CTC (randomisation 2 : 1, respectively). SETTING: A total of 21 NHS hospitals. PARTICIPANTS: Patients aged ≥ 55 years with symptoms suggestive of colorectal cancer (CRC). INTERVENTIONS: CTC, BE and colonoscopy. MAIN OUTCOME MEASURES: For the trial of CTC compared with BE, the primary outcome was the detection rate of CRC and large polyps (≥ 10 mm), with the proportion of patients referred for additional colonic investigation as a secondary outcome. For the trial of CTC compared with colonoscopy, the primary outcome was the proportion of patients referred for additional colonic investigation, with the detection rate of CRC and large polyps as a secondary outcome. Secondary outcomes for both trials were miss rates for cancer (via registry data), all-cause mortality, serious adverse events, patient acceptability, extracolonic pathology and cost-effectiveness. RESULTS: A total of 8484 patients were registered and 5384 were randomised and analysed (BE trial: 2527 BE, 1277 CTC; colonoscopy trial: 1047 colonoscopy, 533 CTC). Detection rates in the BE trial were 7.3% (93/1277) for CTC, compared with 5.6% (141/2527) for BE (p = 0.0390). The difference was due to better detection of large polyps by CTC (3.6% vs. 2.2%; p = 0.0098), with no significant difference for cancer (3.7% vs. 3.4%; p = 0.66). Significantly more patients having CTC underwent additional investigation (23.5% vs. 18.3%; p = 0.0003). At the 3-year follow-up, the miss rate for CRC was 6.7% for CTC (three missed cancers) and 14.1% for BE (12 missed cancers). Significantly more patients randomised to CTC than to colonoscopy underwent additional investigation (30% vs. 8.2%; p < 0.0001). There was no significant difference in detection rates for cancer or large polyps (10.7% for CTC vs. 11.4% for colonoscopy; p = 0.69), with no difference when cancers (p = 0.94) and large polyps (p = 0.53) were analysed separately. At the 3-year follow-up, the miss rate for cancer was nil for colonoscopy and 3.4% for CTC (one missed cancer). Adverse events were uncommon for all procedures. In 1042 of 1748 (59.6%) CTC examinations, at least one extracolonic finding was reported, and this proportion increased with age (p < 0.0001). A total of 149 patients (8.5%) were subsequently investigated, and extracolonic neoplasia was diagnosed in 79 patients (4.5%) and malignancy in 29 (1.7%). In the short term, CTC was significantly more acceptable to patients than BE or colonoscopy. Total costs for CTC and colonoscopy were finely balanced, but CTC was associated with higher health-care costs than BE. The cost per large polyp or cancer detected was £4235 (95% confidence interval £395 to £9656). CONCLUSIONS: CTC is superior to BE for detection of cancers and large polyps in symptomatic patients. CTC and colonoscopy detect a similar proportion of large polyps and cancers and their costs are also similar. CTC precipitates significantly more additional investigations than either BE or colonoscopy, and evidence-based referral criteria are needed. Further work is recommended to clarify the extent to which patients initially referred for colonoscopy or BE undergo subsequent abdominopelvic imaging, for example by computed tomography, which will have a significant impact on health economic estimates. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95152621.

Identification of Extracolonic Pathologies by Computed Tomographic Colonography in Colorectal Cancer Symptomatic Patients.

BACKGROUND & AIMS: Symptoms suggestive of colorectal cancer may originate outside the colorectum. Computed tomographic colonography (CTC) is used to examine the colorectum and abdominopelvic organs simultaneously. We performed a prospective randomized controlled trial to quantify the frequency, nature, and consequences of extracolonic findings. METHODS: We studied 5384 patients from 21 UK National Health Service hospitals referred by their family doctor for the investigation of colorectal cancer symptoms from March 2004 through December 2007. The patients were assigned randomly to groups that received the requested test (barium enema or colonoscopy, n = 3574) or CTC (n = 1810). We determined the frequency and nature of extracolonic findings, subsequent investigations, ultimate diagnosis, and extracolonic cancer diagnoses 1 and 3 years after testing patients without colorectal cancer. RESULTS: Extracolonic pathologies were detected in 959 patients by CTC (58.7%), in 42 patients by barium enema analysis (1.9%), and in no patients by colonoscopy. Extracolonic findings were investigated in 142 patients (14.2%) and a diagnosis was made for 126 patients (88.1%). Symptoms were explained by extracolonic findings in 4 patients analyzed by barium enema (0.2%) and in 33 patients analyzed by CTC (2.8%). CTC identified 72 extracolonic neoplasms, however, barium enema analysis found only 3 (colonoscopy found none). Overall, CTC diagnosed extracolonic neoplasms in 72 of 1634 patients (4.4%); 26 of these were malignant (1.6%). There were significantly more extracolonic malignancies detected than expected 1 year after examination, but these did not differ between patients evaluated by CTC (22.2/1000 person-years), barium enema (26.5/1000 person-years; P = .43), or colonoscopy (32.0/1000 person-years; P = .88). CONCLUSIONS: More than half of the patients with symptoms of colorectal cancer are found to have extracolonic pathologies by CTC analysis. However, the proportion of patients found to have extracolonic malignancies after 1 year of CTC examination is not significantly greater than after barium enema or colonoscopy examinations. International Standard Randomised Controlled Trials no: 95152621.isrctn.com.

Computed tomographic colonography versus barium enema for diagnosis of colorectal cancer or large polyps in symptomatic patients (SIGGAR): a multicentre randomised trial.

BACKGROUND: Barium enema (BE) is widely available for diagnosis of colorectal cancer despite concerns about its accuracy and acceptability. Computed tomographic colonography (CTC) might be a more sensitive and acceptable alternative. We aimed to compare CTC and BE for diagnosis of colorectal cancer or large polyps in symptomatic patients in clinical practice. METHODS: This pragmatic multicentre randomised trial recruited patients with symptoms suggestive of colorectal cancer from 21 UK hospitals. Eligible patients were aged 55 years or older and regarded by their referring clinician as suitable for radiological investigation of the colon. Patients were randomly assigned (2:1) to BE or CTC by computer-generated random numbers, in blocks of six, stratified by trial centre and sex. We analysed the primary outcome-diagnosis of colorectal cancer or large (≥10 mm) polyps-by intention to treat. The trial is an International Standard Randomised Controlled Trial, number 95152621. FINDINGS: 3838 patients were randomly assigned to receive either BE (n=2553) or CTC (n=1285). 34 patients withdrew consent, leaving for analysis 2527 assigned to BE and 1277 assigned to CTC. The detection rate of colorectal cancer or large polyps was significantly higher in patients assigned to CTC than in those assigned to BE (93 [7.3%] of 1277 vs 141 [5.6%] of 2527, relative risk 1.31, 95% CI 1.01-1.68; p=0.0390). CTC missed three of 45 colorectal cancers and BE missed 12 of 85. The rate of additional colonic investigation was higher after CTC than after BE (283 [23.5%] of 1206 CTC patients had additional investigation vs 422 [18.3%] of 2300 BE patients; p=0.0003), due mainly to a higher polyp detection rate. Serious adverse events were rare. INTERPRETATION: CTC is a more sensitive test than BE. Our results suggest that CTC should be the preferred radiological test for patients with symptoms suggestive of colorectal cancer. FUNDING: NIHR Health Technology Assessment Programme, NIHR Biomedical Research Centres funding scheme, Cancer Research UK, EPSRC Multidisciplinary Assessment of Technology Centre for Healthcare, and NIHR Collaborations for Leadership in Applied Health Research and Care.

Patient-reported outcomes following flexible sigmoidoscopy screening for colorectal cancer in a demonstration screening programme in the UK.

OBJECTIVES: Flexible sigmoidoscopy (FS) screening for colorectal cancer will be introduced into the National Cancer Screening Programmes in England in 2013. Patient-reported outcome measures (PROMs) from trial participants indicate high acceptability and no adverse physical or psychological consequences, but this may not generalize to routine screening in the community. This study examined PROMs in a community-based FS screening programme. METHODS: Eligible adults aged 58-59 (n = 2016) registered at 34 London general practices were mailed a National Health Service-endorsed invitation to attend FS screening. Pain and side-effects were assessed in a 'morning-after' questionnaire, and satisfaction was assessed in a three-month follow-up questionnaire. Anxiety, self-rated health and colorectal symptoms were assessed at prescreening and follow-up. RESULTS: In total, 1020 people attended screening and were included in the current analyses, of whom 913 (90%) returned the morning-after questionnaire, and 674 (66%) the follow-up questionnaire. The prescreening questionnaire had been completed by 751 (74%) of those who attended. The majority (87%) of respondents reported no pain or mild pain, and the most frequent side-effect (wind) was only experienced more than mildly by 16%. Satisfaction was extremely high, with 98% glad they had the test; 97% would encourage a friend to have it. From prescreening to follow-up there were no changes in anxiety or self-rated health, and the number of colorectal symptoms declined. Satisfaction and changes in wellbeing were not moderated by gender, deprivation, ethnicity or screening outcome. CONCLUSIONS: PROMs indicate high acceptability of FS screening in 58-59 year olds, with no adverse effects on colorectal symptoms, health status or psychological wellbeing.

Patient acceptability of CT colonography compared with double contrast barium enema: results from a multicentre randomised controlled trial of symptomatic patients.

OBJECTIVES: To determine patient acceptability of barium enema (BE) or CT colonography (CTC). METHODS: After ethical approval, 921 consenting patients with symptoms suggestive of colorectal cancer who had been randomly assigned and completed either BE (N = 606) or CTC (N = 315) received a questionnaire to assess experience of the clinical episode including bowel preparation, procedure and complications. Satisfaction, worry and physical discomfort were assessed using an adapted version of a validated acceptability scale. Non-parametric methods assessed differences between the randomised tests and the effect of patient characteristics. RESULTS: Patients undergoing BE were significantly less satisfied (median 61, interquartile range [IQR] 54-67 vs. median 64, IQR 56-69; p = 0.003) and experienced more physical discomfort (median 40, IQR 29-52 vs. median 35.5, IQR 25-47; p < 0.001) than those undergoing CTC. Post-test, BE patients were significantly more likely to experience 'abdominal pain/cramps' (68% vs. 57%; p = 0.007), 'soreness' (57% vs. 37%; p < 0.001), 'nausea/vomiting' (16% vs. 8%; p = 0.009), 'soiling' (31% vs. 23%; p = 0.034) and 'wind' (92% vs. 84%; p = 0.001) and in the case of 'wind' to also rate it as severe (27% vs. 15%; p < 0.001). CONCLUSION: CTC is associated with significant improvements in patient experience. These data support the case for CTC to replace BE.

Design of a multicentre randomized trial to evaluate CT colonography versus colonoscopy or barium enema for diagnosis of colonic cancer in older symptomatic patients: the SIGGAR study.

BACKGROUND AND AIMS: The standard whole-colon tests used to investigate patients with symptoms of colorectal cancer are barium enema and colonoscopy. Colonoscopy is the reference test but is technically difficult, resource intensive, and associated with adverse events, especially in the elderly. Barium enema is safer but has reduced sensitivity for cancer. CT colonography ("virtual colonoscopy") is a newer alternative that may combine high sensitivity for cancer with safety and patient acceptability. The SIGGAR trial aims to determine the diagnostic efficacy, acceptability, and economic costs associated with this new technology. METHODS: The SIGGAR trial is a multi-centre randomised comparison of CT colonography versus standard investigation (barium enema or colonoscopy), the latter determined by individual clinician preference. Diagnostic efficacy for colorectal cancer and colonic polyps measuring 1 cm or larger will be determined, as will the physical and psychological morbidity associated with each diagnostic test, the latter via questionnaires developed from qualitative interviews. The economic costs of making or excluding a diagnosis will be determined for each diagnostic test and information from the trial and other data from the literature will be used to populate models framed to summarise the health effects and costs of alternative approaches to detection of significant colonic neoplasia in patients of different ages, prior risks and preferences. This analysis will focus particularly on the frequency, clinical relevance, costs, and psychological and physical morbidity associated with detection of extracolonic lesions by CT colonography. RESULTS: Recruitment commenced in March 2004 and at the time of writing (July 2007) 5025 patients have been randomised. A lower than expected prevalence of end-points in the barium enema sub-trial has caused an increase in sample size. In addition to the study protocol, we describe our approach to recruitment, notably the benefits of extensive piloting, the use of a sham-randomisation procedure, which was employed to determine whether centres interested in participating were likely to be effective in practice, and the provision of funding for dedicated sessions for a research nurse at each centre to devote specifically to this trial. TRIAL REGISTRATION: Current Controlled Trials ISRCTN95152621.