The Fast Track FIT study: diagnostic accuracy of faecal immunochemical test for haemoglobin in patients with suspected colorectal cancer.

BACKGROUND: The faecal immunochemical test (FIT) is now available to support clinicians in the assessment of patients at low risk of colorectal cancer (CRC) and within the bowel cancer screening programme. AIM: To determine the diagnostic accuracy of FIT for CRC and clinically significant disease in patients referred as they were judged by their GP to fulfil National Institute for Health and Care Excellence guideline 12 (NG12) criteria for suspected CRC. DESIGN AND SETTING: Patients referred from primary care with suspected CRC, meeting NG12 criteria, to 12 secondary care providers in Yorkshire and Humber were asked to complete a FIT before investigation. METHOD: The diagnostic accuracy of FIT based on final diagnosis was evaluated using receiver operating characteristics analysis. This permitted a statistically optimal cut-off value for FIT to be determined based on the maximisation of sensitivity and specificity. Clinicians and patients were blinded to the FIT results. RESULTS: In total, 5040 patients were fully evaluated and CRC was detected in 151 (3.0%). An optimal cut-off value of 19 µg Hb/g faeces for CRC was determined, giving a sensitivity of 85.4% (95% confidence interval [CI] = 78.8% to 90.6%) and specificity of 85.2% (95% CI = 84.1% to 86.2%). The negative predictive value at this cut-off value was 99.5% (95% CI = 99.2% to 99.7%) and the positive predictive value 15.1% (95% CI = 12.8% to 17.7%). Sensitivity and specificity of FIT for CRC and significant premalignant polyps at this cut-off value were 62.9% (95% CI = 57.5% to 68.0%) and 86.4% (95% CI = 85.4% to 87.4%), respectively; and when including all organic enteric disease were 35.7% (95% CI = 32.9% to 38.5%) and 88.6% (95% CI = 87.5% to 89.6%), respectively. CONCLUSION: FIT used in patients fulfilling NG12 criteria should allow for a more personalised CRC risk assessment. FIT should permit effective, patient-centred decision-making to inform the need for, type, and timing of further investigation.

Audit of the impact of the York faecal calprotectin care pathway on colonoscopy activity.

BACKGROUND: The York faecal calprotectin care pathway (YFCCP) was developed to optimise effective primary care differentiation between irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD). We undertook an audit of colonoscopy activity at York Teaching Hospitals after the introduction of the YFCCP, to assess its impact. METHODS: Faecal calprotectin (FC) results were reconciled with colonoscopy activity in patients 18-60 years after the implementation of the YFCCP. This permitted individual patient tracking of their FC values, the timing of those requests by primary care, the date of subsequent referral and investigation and the end clinical diagnoses. RESULTS: Primary care uptake of FC increased fourfold with the introduction of the YFCCP. Following implementation, FC-related referrals for colonoscopy fell from 24% to 13%. The number of patients needed to colonoscope to diagnose organic colonic disease (IBD, significant adenomatous polyps or colorectal cancer) fell from 6.8 to 3.8 when the YFCCP was applied. This represents a cost saving of £41 015 per thousand patients tested in primary care. We estimate that outpatient time to diagnosis fell from a median of 41 to 29 days. CONCLUSION: This audit of FC activity and colonoscopy outcomes provides substantial supportive evidence for the effectiveness of the YFCCP. Popular in primary care, it has led to a reduction in referrals. The diagnostic accuracy determined in this audit is in line with earlier evaluations. Accepting the weaknesses of audit we conclude that this evaluation likely underestimates the benefits of the YFCCP in terms of resource use saving and time to diagnosis.

Evaluation of sample stability for a quantitative faecal immunochemical test and comparison of two sample collection approaches.

Background Faecal immunochemical testing is increasingly being used to triage symptomatic patients for suspected colorectal cancer. However, there are limited data on the effect of preanalytical factors on faecal haemoglobin when measured by faecal immunochemical testing. The aim of this work was to evaluate the stability of faecal haemoglobin in faeces and to compare two methods of faecal haemoglobin sampling for faecal immunochemical testing. Methods Six patients provided faeces for faecal haemoglobin measurement which were transferred into specialized collection devices at baseline and at 1, 2, 3 and 7 days after storage at either room temperature or 4°C. A total of 137 patients returned both faeces transferred into the specialized collection device and faeces in a standard collection pot. A quantitative immunoturbidometric method was used to measure faecal haemoglobin and results were compared categorically. Discrepant results were assessed against diagnosis. Results Faecal haemoglobin concentration declined rapidly within a day of storage at room temperature but results remained ≥10 µg Hb/g faeces in 5/6 patients after two days. A faecal haemoglobin result ≥10 µg Hb/g faeces was obtained in 4/6 patients after storage for seven days at 4°C. Results obtained when patients used specialized collection devices were significantly different from results obtained when faeces was transferred into the specialized collection device in the laboratory. Conclusion There is considerable heterogeneity in the sample stability of faecal haemoglobin; therefore, samples should be transferred rapidly into specialized collection devices to prevent false-negative results. Use of collection devices by patients can lead to false-positive results compared with their use in a laboratory.

Diagnostic accuracy of one or two faecal haemoglobin and calprotectin measurements in patients with suspected colorectal cancer.

BACKGROUND: The role of faecal biomarkers in patients at 'high risk' of colorectal cancer (CRC) is not yet defined. Pre-analytical factors, such as heterogeneity of biomarker distribution within faeces, may influence their optimisation in clinical practice. We undertook to determine whether repeat or combined biomarker testing improves diagnostic accuracy for CRC or clinically significant disease. METHODS: Patients referred with suspected CRC provided two separate faecal samples each for faecal immunochemical testing (FIT) and faecal calprotectin (FC) prior to investigation. Diagnostic accuracy of FIT and FC were evaluated based on final diagnoses. RESULTS: Five hundred fifteen patients completed a full colorectal evaluation. The optimal cut-off for CRC using a single FIT was ≥12 µgHb/g faeces (84.6% sensitivity, 88.5% specificity). For two FIT, the cut-off was ≥43 µgHb/g faeces if either and ≥2 µgHb/g faeces if both were positive. There was no advantage in their diagnostic accuracy compared with a single FIT. FC had a lower diagnostic accuracy for CRC than FIT, which was not improved by repeat FC. No benefit was identified with FIT-FC combined. For CRC, significant adenomatous polyps and organic enteric disease combined, FIT and FC performed similarly to each other but were poorer predictors (AUC 0.677 and 0.660). There was no uplift in diagnostic accuracy when the tests were repeated or combined. CONCLUSION: This study supports using a single FIT at a cut-off close to that recommended by NICE DG30 to improve diagnostic accuracy for 'two-week wait' patients referred with suspected CRC.

Faecal calprotectin in patients with suspected colorectal cancer: a diagnostic accuracy study.

BACKGROUND: NICE guidance exists for the use of faecal calprotectin (FC) when irritable bowel syndrome or inflammatory bowel disease are suspected. Often, however, colorectal cancer is considered within the differential. Should FC have a high diagnostic accuracy for colorectal cancer, it may be applicable as a primary care screening test for all patients with lower gastrointestinal symptoms. AIM: To determine the negative and positive predictive value (NPV/PPV) of FC in patients referred from primary care with suspected colorectal cancer. DESIGN AND SETTING: A diagnostic accuracy study conducted at a single secondary care site METHOD: Consenting patients referred with suspected colorectal cancer within the '2-week wait' pathway provided a stool sample for FC prior to investigation. FC levels were reconciled with end diagnoses: cancer, adenomatous polyps ≥10 mm, and all enteric organic disease. RESULTS: A total of 654 patients completed the evaluation; median age 69 years, female 56%. The NPV for colorectal cancer was 98.6% and 97.2% when including polyps ≥10 mm. The PPV for all organic enteric disease was 32.7%. The diagnostic yield for cancer based on clinical suspicion was 6.3%. By altering the FC cut-off to fix the NPV at 97.0%, the PPV for cancer increased from 8.7% to 13.3%. CONCLUSION: FC has a high NPV for colorectal cancer and significant polyps in patients with suspected cancer. In total, 27.8% of patients had a normal FC and could safely have been spared a '2-week wait' referral. The addition of FC testing into the current symptom-based assessment has the potential to increase colorectal cancer detection rate yet be clinically and cost effective.

Evaluation of a faecal calprotectin care pathway for use in primary care.

BACKGROUND: National Institute for Health and Care Excellence have recommended faecal calprotectin (FC) testing as an option in adults with lower gastrointestinal symptoms for whom specialist investigations are being considered, if cancer is not suspected and it is used to support a diagnosis of inflammatory bowel disease (IBD) or irritable bowel syndrome. York Hospital and Vale of York Clinical Commissioning Group have developed an evidence-based care pathway to support this recommendation for use in primary care. It incorporates a higher FC cut-off value, a 'traffic light' system for risk and a clinical management pathway. OBJECTIVES: To evaluate this care pathway. METHODS: The care pathway was introduced into five primary care practices for a period of six months and the clinical outcomes of patients were evaluated. Negative and positive predictive values (NPV and PPV) were calculated. GP feedback of the care pathway was obtained by means of a web-based survey. Comparator gastroenterology activity in a neighbouring trust was obtained. RESULTS: The care pathway for FC in primary care had a 97% NPV and a 40% PPV. This was better than GP clinical judgement alone and doubled the PPV compared with the standard FC cut-off (250 mcg/g and were diagnosed by 'straight to test' colonoscopy within three weeks. The care pathway was considered helpful by GPs and delivered a higher diagnostic yield after secondary care referral (21%) than the conventional comparator pathway (5%). CONCLUSIONS: A care pathway for the use of FC that incorporates a higher cut-off value, a 'traffic light' system for risk and supports clinical decision making can be achieved safely and effectively. It maintains the balance between a high NPV and an acceptable PPV. A modified care pathway for the use of FC in primary care is proposed.