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Symptom or faecal immunochemical test based referral criteria for colorectal cancer detection in symptomatic patients: a diagnostic tests study

Abstract

Background

Symptom based referral criteria for colorectal cancer (CRC) detection are the cornerstone of the strategy to improve prognosis in CRC. In 2017, the National Institute for Health and Care Excellence (NICE) updated their referral criteria (2017 NG12). Recently, several studies have evaluated the faecal haemoglobin (f-Hb) concentration in this setting. The aim of this study is to evaluate the diagnostic accuracy of the 2017 NG12 referral criteria and to compare them with the CG27 referral criteria, the f-Hb concentration and two f-Hb based prediction model: COLONPREDICT and FAST Score.

Methods

This is a post-hoc diagnostic test study performed within the COLONPREDICT study database (1572 patients, CRC prevalence 13.6%). We assessed symptoms, the 2017 NG12 and CG27 referral criteria and determined the f-Hb before performing a colonoscopy. We compared the discriminatory ability using the area under the curve (AUC) and the sensitivity and specificity at pre-stablished thresholds with the McNemar’s test.

Results

The 2017 NG12 referral criteria discriminatory ability (AUC 0.53; 95% confidence interval- CI 0.49–0.57) was inferior to the CG27 version (AUC 0.59; 95% CI 0.55–0.63; p = 0.01), the f-Hb concentration (AUC 0.86; 95% CI 0.84–0-89; p < 0.001), the COLONPREDICT Score (AUC 0.92; 95% CI 0.91–0.94; p < 0.001) or the FAST Score (AUC 0.87; 95% CI 0.85–0.89; p < 0.001). The number of patients meeting each criteria were as follows: 2017 NG12 and CG27 = 94.1% and 52.2%; f-Hb ≥20 and ≥ 10 μg/g faeces = 38.6 and 44.3%; COLONPREDICT Score ≥ 5.6 and ≥ 3.2 = 29.4 and 63.2% and FAST Score ≥ 4.50 and ≥ 2.12 = 37.1 and 87.0%. The 2017 NG12 criteria were more sensitive (100%) than the CG27 criteria (68.2%), the f-Hb (≥20 μg/g) (91.2%), the f-Hb (≥10 μg/g) (93.5%), the COLONPREDICT Score (≥5.6) (90.1%) and the FAST Score (≥4.50) (89.8%) (p ≤ 0.001) and equivalent to the COLONPREDICT Score (≥3.5) (99.5%) or the FAST Score (≥2.12) (100.0%) (p = 1). However, their specificity (6.8%) was significantly lower than any of the evaluated criteria (50.3%, 69.6%, 63.4%, 78.7%, 45.8%, 71.3%, 13.9%; p < 0.001).

Conclusion

Referral criteria based on f-Hb measurement, either as a single test or within prediction models, are more accurate than symptom-based referral criteria for CRC detection in symptomatic patients.

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Background

Colorectal cancer (CRC) is the third most common cancer worldwide and the second leading cause of cancer-related death [1]. Two strategies are widely used to detect the disease at an early stage and, thus, improve the prognosis: CRC screening and early diagnosis strategies in symptomatic patients [2, 3]. Although screening programmes have been progressively implemented, most CRC are still detected when symptoms become apparent [4]. In addition, although gastrointestinal symptoms are extremely common in the population, the probability of CRC detection associated with any one symptom is low [5,6,7]. Thus, risk classification scores have been developed based on symptoms to determine which patients are most at risk of CRC with the aim of reducing this interval between the initial consultation and diagnostic colonoscopy [8, 9].

In this regard, one of the best known referral criteria for CRC detection are the National Institute for Health and Care Excellence (NICE) referral guideline for suspected cancer (CG27) [3]. This referral system has been extensively evaluated showing a low specificity and a variable sensitivity for CRC detection [6, 10,11,12]. In order to improve these results, the updated version of 2015 (NG12) introduced two significant changes. First, they recommended referral for those symptoms with a positive predictive value of 3% instead of previous 5%. Second, for the first time, testing for occult blood in faeces was recommended in several symptom scenarios with a positive predictive value below 3% [13]. However, the guideline did not recommend any particular method to determine occult blood in faeces.

Faecal immunochemical tests for haemoglobin (FIT) allow for quantitation of faecal haemoglobin concentration (f-Hb). FIT has proven to be the best currently available non-invasive test for CRC screening in asymptomatic individuals and an excellent test for rule-in of CRC and rule-out of significant colonic lesions (SCL) in patients presenting with lower gastrointestinal symptoms [14,15,16,17,18,19,20,21]. On the basis of the available evidence [22], the NICE diagnostic guidance (DG30) recommends the use of FIT with a 10 μg Hb/g faeces to guide referral for colorectal cancer in primary care [23]. However, the effect of the NG12 is not well understood and only one study has evaluated the diagnostic accuracy of this guidance [24]. In July 2017, NG 12 was amended and testing for occult blood in faeces was recommended in patients without rectal bleeding but with unexplained symptoms that do not meet the criteria for a suspected cancer pathway [13].

We have recently developed and validated two f-Hb based prediction models for CRC detection: COLONPREDICT and FAST. The database of the COLONPREDICT Score derivation cohort [25, 26]. is an excellent platform to compare the most widely symptom based referral criteria with the f-Hb concentration based strategies. In this database, an extensive collection of information regarding symptoms as well as several blood and faecal determinations are included. This information allowed us to perform a post hoc analysis in order to evaluate the diagnostic accuracy of the 2017 NG12, compare these criteria with the CG27, the f-Hb concentration and two CRC prediction models based on the f-Hb concentration: COLONPREDICT and FAST Scores [25, 26].

Methods

Study design

The current study is a post hoc analysis performed within the COLONPREDICT study: a multicentre, cross-sectional, blinded study of diagnostic tests. The study aimed to create and validate a CRC prediction index based on available biomarkers, clinical and demographical data. We performed this post hoc analysis in the 1572 patients included in the derivation previously described [25].

Brief description of the COLONPREDICT study

The details of the study have been described extensively elsewhere and are summarized here [25, 26]. We used the Colonoscopy Research into Symptom Prediction questionnaire (CRISP) to record symptoms and demographic data [27]. Based on this questionnaire, they determined if patients met the CG27 referral criteria for CRC detection [3]. f-Hb concentration was assessed using the automated OC-SENSOR MICRO analyser (Eiken Chemical Co., Ltd., Tokyo, Japan). The faeces for the f-Hb determination were collected using the OC-Sensor probe. Moreover, we determined blood haemoglobin (b-Hb) and mean corpuscular volume with a Beckman Coulter Autoanalyzer (Beckman Coulter Inc., CA, USA). Colonoscopy was performed blind for the questionnaire and analytical results.

2017 NG12 referral criteria and the f-Hb based prediction models calculation

On the basis of the information obtained from the CRISP questionnaire and the analysis performed (f-Hb, b-Hb and mean corpuscular volume), we determined which of the 2017 NG12 criteria for CRC suspicion were met. Two researchers (JMH and JC) independently decided the equivalence between each NICE criteria and the information collected. Finally, they reached a consensus version. NG12 referral criteria are shown in Table 1 [13]. We considered a positive faecal occult blood test if the f-Hb concentration was ≥10 μg Hb/g faeces.

Table 1 Criteria to refer people using a suspected cancer pathway referral for CRC according to the NG12 referral criteria. The number of patients meeting each of the referral criteria is shown

COLONPREDICT score is a CRC prediction model based on a multivariable logistic regression analysis [25]. The COLONPREDICT score is based in eleven variables and the mathematical formula is as follows: 0.789 x rectal bleeding + 0.536 x change in bowel habit + 2.694 x rectal mass − 1.283 x benign anorectal lesions + 2.831 x f-Hb ≥20 μg Hb/g faeces + 1.561 x b-Hb (< 10 g/dL) + 0.588 x b-Hb (10–12 g/dL) + 1.511 x CEA ≥3 ng/mL + 0.040 x age (years) + 0.813 x sex (male) -2.073 x previous colonoscopy (last 10 years) -0.849 x continuous treatment with aspirin. It shows a high diagnostic accuracy for CRC detection. Two thresholds have been defined with 90% and 99% sensitivity for CRC: 5.6 and 3.5.

FAST Score is a CRC prediction model based on a multivariable logistic regression analysis [26]. The FAST score is based on three variables and the mathematical formula is as follows: 0 x f-Hb (0) μg Hb/g faeces 0.684 x f-Hb (1, 19) + 2.824 x f-Hb [20, 200) μg Hb/g faeces + 4.184 x f-Hb ≥200 μg Hb/g faeces + 0.031 x age (years) + 0.479 x sex (male). Two thresholds have been defined with 90% and 99% sensitivity for CRC: 4.50 and 2.12.

Outcomes

The main outcome was CRC detection. According to previous studies evaluating FIT in symptomatic patients, [14,15,16,17,18,19,20,21] we considered significant colonic lesion (SCL) detection as the secondary outcome. We defined SCL as CRC, advanced adenoma (≥10 mm, villous histology, high-grade dysplasia), polyposis (> 10 polyps of any histology, including serrated lesions), histologically confirmed colitis (any aetiology), polyps ≥10 mm, complicated diverticular disease (diverticulitis, bleeding), colonic ulcer and/or bleeding angiodysplasia.

Statistical analysis

First, we performed a descriptive analysis of the population included in the study. In order to determine differences in diagnostic accuracy between the NG12 referral criteria and the rest of diagnostic criteria, the CG27 referral criteria, the f-Hb concentration, the COLONPREDICT and the FAST score we performed two analysis. First, we determined the number of individuals with a positive result and the sensitivity and the specificity for CRC and SCL detection. We determined if the differences between the sensitivity and the specificity of the NG12 referral criteria and the rest of diagnostic criteria, CG27 referral criteria, the COLONPREDICT and the FAST scores at the pre-stablished thresholds and the f-Hb at a 10 and 20 μg Hb/g faeces concentration threshold, were statistically significant using the McNemar’s test. Finally, we also calculated the positive and negative predictive value (PPV, NPV), the positive and negative likelihood ratios (LR) and the diagnostic Odds Ratio (OR) of all the diagnostic tests. Diagnostic OR is defined as the odds of positivity in subjects with disease relative to the odds in subjects without disease.

In a second step, we evaluated the discriminatory ability using receiver-operating characteristic (ROC) curves for CRC and SCL diagnosis, and we calculated the area under the curve (AUC). We determined whether there were statistically significant differences using the chi-square test of homogeneity of areas. Additionally, we determined if there were differences in the discriminatory ability of each of the diagnostic criteria according to the healthcare level referring the patient to colonoscopy. Primary healthcare referral was determined when a general practitioner was requesting the colonoscopy and secondary healthcare referral was determined when a specialist (gastroenterologist, surgeon..) was requesting the exploration.

We report differences with 95% confidence intervals (CI) and their significance. We consider a p-value < 0.05 statistically significant. We carried out the analyses using the IBM SPSS Statistics for Windows version 21.0 (IBM Corp, Armonk, USA) and EPIDAT 3.1 (Dirección Xeral de Saúde Pública, Santiago de Compostela, Spain).

Results

Description of the cohort

Among the 1572 patients included in the derivation cohort of the COLONPREDICT, a CRC was detected in 214 (13.6%) patients and a SCL in 463 (29.5%) patients: advanced adenomas in 251 (16.0%), a polyp ≥10 mm with non-adenoma histology in 6 (0.4%), colitis in 36 (2.3%) and other SCLs in 6 (0.4%) patients. Direct referrals from primary care to endoscopic evaluation accounted for 22.9% of the patients included.

As we show in the Table 1, 1,479 out of the 1572 (94.1%) met at least one of the 2017 NG12 referral criteria. In contrast, 52.2% of the patients met any of the CG27 referral criteria, 38.7% had a f-Hb concentration ≥ 20 μg Hb/g faeces, 44.4% had a f-Hb concentration ≥ 10 μg Hb/g faeces, 30.9% had a COLONPREDICT Score ≥ 5.6, 60.5% had a COLONPREDICT Score ≥ 3.5, 37.1% had a FAST Score ≥ 4.50 and 88.0% had a FAST Score ≥ 2.12.

Analysis of the diagnostic accuracy

The sensitivity of the 2017 NG12 referral criteria for CRC detection reaches 100% at the expense of a low specificity (6.8%). As we show in the Table 2, the sensitivity of the 2017 NG12 referral criteria is superior to the sensitivity of the CG27 referral criteria, the f-Hb (≥20 μg Hb/g and ≥ 10 μg Hb/g faeces), the COLONPREDICT Score at a 5.6 threshold (p < 0.001) and the FAST Score at a 4.50 threshold. In contrast, the sensitivity is similar to the COLONPREDICT Score at a 3.2 threshold and the FAST Score at a 2.12 threshold (p = 1) and the specificity is inferior to any of the other criteria (p < 0.001). The rest of the diagnostic accuracy analysis is displayed in Table 2.

Table 2 Evaluation of the diagnostic accuracy of the evaluated strategies for colorectal cancer detection

On the other hand, 2017 NG12 referral criteria allows the diagnosis of 98.9% of SCL. As in the diagnostic accuracy for CRC detection, the specificity is extremely low (7.9%). As we show in the Table 3, the sensitivity of the 2017 NG12 referral criteria is similar to the FAST Score at a 2.12 threshold (p = 1) and superior the rest of the evaluated criteria. In contrast, the specificity of the 2017 NG12 criteria is inferior to any of the additional criteria evaluated (p < 0.001). We show the PPV, NPV, positive and negative LR and the diagnostic OR in Table 2.

Table 3 Evaluation of the diagnostic accuracy of the evaluated strategies for significant colonic lesion detection

Analysis of the discriminatory ability

The analysis of the discriminatory ability for CRC detection of the NICE referral criteria, the f-Hb concentration, the COLONPREDICT and the FAST Score is shown in Fig. 1. The discriminatory ability of the 2017 NG12 referral criteria is inferior to any of the evaluated criteria in the Chi-square homogeneity test comparison of AUC. Additionally, we found no differences in the performance of each diagnostic test in the evaluation of the discriminatory ability according to the healthcare referring the patient to colonoscopy: 2017 NG12 referral criteria (primary = 0.53, 95% CI 0.46–0.60; secondary = 0.53, 95% CI 0.48–0.58; p = 0.1), CG27 referral criteria (primary = 0.60, 95% CI 0.54–0.66; secondary = 0.59, 95% CI 0.55–0.63; p = 0.7), f-Hb concentration (primary = 0.85, 95% CI 0.80–0.89; secondary = 0.86, 95% CI 0.83–0.89; p = 0.5), COLONPREDICT Score (primary = 0.90, 95% CI 0.86–0.94; secondary = 0.93, 95% CI 0.91–0.95; p = 0.1), FAST Score (primary = 0.84, 95% CI 0.79–0.89; secondary = 0.88, 95% CI 0.85–0.90; p = 0.1). Fig. 2 shows the discriminatory ability for SCL detection of the diagnostic tests evaluated. The discriminatory ability of the 2017 NG12 referral criteria is similar to the CG27 referral criteria and inferior to the rest of the evaluated criteria in the Chi-square homogeneity test comparison of AUC.

Fig. 1
figure 1

ROC curves of the NICE referral criteria, faecal haemoglobin concentration and the COLONPREDICT and FAST Scores for colorectal cancer detection. The area under the curve of the ROC curves are shown. 1Significance of the discriminatory ability differences when compared with the NG12 referral criteria in Chi square homogeneity test. Differences with p < 0.05 are considered statistically significant. ROC, Receiver-operating characteristics; NICE, National Institute for Health and Care Excellence

Fig. 2
figure 2

ROC curves of the NICE referral criteria, faecal haemoglobin concentration and the COLONPREDICT and FAST Scores for significant colonic lesion detection. The area under the curve of the ROC curves are shown. 1Significance of the discriminatory ability differences when compared with the NG12 referral criteria in Chi square homogeneity test. Differences with p < 0.05 are considered statistically significant. ROC, Receiver-operating characteristics; NICE, National Institute for Health and Care Excellence

Discussion

Summary

We have evaluated the diagnostic accuracy of the 2017 NG12 referral criteria for suspected CRC. As we clearly show, these updated criteria are more sensitive than CG27 version. However, they produce a marked increase in the number of patients meeting them and a reduction in the specificity. Furthermore, we had the opportunity to compare them with the f-Hb concentration and two f-Hb based prediction model. As we clearly show, both diagnostic tools have a higher discriminatory ability than the NICE referral criteria.

Strengths and limitations

We have used a wide cohort of consecutive patients referred to colonoscopy due to gastrointestinal symptoms. Patients were evaluated homogenously using a symptom questionnaire and several analytics, including a FIT, were performed before colonoscopy. This questionnaire allowed us to gather all the details regarding type of symptoms, duration and evolution. Thus, we could evaluate the 2017 NG12 referral criteria for suspected CRC for the first time. Furthermore, we have been able to evaluate the use of FIT, with the 10 μg Hb/g faeces, as recommended in the DG30 [23]. On the other hand, our study has several limitations that must be taken in consideration. We cannot exclude a risk of bias of selection, as long as the symptomatic patients included in the study were previously selected for colonoscopy evaluation. However, we have included all consecutive patients referred both from primary and secondary healthcare to colonoscopy.

Comparison with existing literature

The update of the NICE referral criteria is based on reducing the PPV threshold required to refer patients from primary care using a suspected cancer pathway referral. The guideline development group agreed to use a threshold value of 3% PPV to underpin their recommendations [13]. So, those patients with symptoms (i.e ≥ 40 years with unexplained weight loss) with a PPV > 3% for CRC should be referred for further testing. Our results clearly demonstrate that this strategy increases the sensitivity for CRC detection in comparison with previous criteria. However, these criteria certainly introduce a risk of over investigation. In fact, what our analysis confirms is that the discriminatory ability of any group of symptoms for CRC detection is suboptimal [6].

An additional innovation of the 2017 NG12 referral criteria is the inclusion of the faecal occult blood test in the evaluation of symptomatic patients. However, its use is only limited to patients without rectal bleeding and with unexplained symptoms that do not meet the criteria for a suspected cancer pathway referral [13]. Our results confirm the data previously published: the f-Hb concentration measured with a FIT shows a higher discriminatory ability for CRC detection than the NICE referral criteria [14,15,16,17,18,19]. So, probably, the strategy for the evaluation of the risk of CRC detection in symptomatic patients should be based on the f-Hb concentration irrespective of symptoms. Actually, in the COLONPREDICT Score, patients with a f-Hb concentration ≥ 20 μg Hb/g faeces have 17.0 times more risk of CRC detection. In contrast, patients with rectal bleeding or a change in bowel habit have 2.2 and 1.7 times more risk of CRC detection, respectively [25].

Recently, an article has evaluated the diagnostic accuracy of the 2017 NG12 referral criteria for CRC and SCL detection and compared these criteria with the f-Hb concentration [24]. This study used the database of three diagnostic tests studies evaluating FIT in symptomatic patients [15, 17, 19]. and shows that the discriminatory ability of the 2017 NG12 referral criteria are inferior to the f-Hb concentration. This cohort has significant differences with ours: the prevalence of symptoms related to CRC diagnosis, rectal bleeding, changes in bowel habit, iron-deficiency anaemia or rectal mass, is inferior as well as the prevalence of CRC or SCL. Probably, these differences are responsible for the differences in the number of patients that meet 2017 NG12 referral criteria and in the inferior discriminatory ability documented in our study. However, are results are consistent in the comparison of the 2017 NG12 referral criteria with the f-Hb concentration.

Implications for research and/or practice

One of the main lessons learned in these years from the CRC screening programs is that lack of symptoms or the presence of non-specific symptoms do not exclude a CRC in adult population. Up to 20% of the incident CRC are detected in asymptomatic patients within a CRC screening program based in a guaiac faecal occult blood test [4]. So, the strategies for CRC detection in symptomatic patients should determine which patients require urgent referral, which require a normal referral and, finally, in what situations no additional evaluation is required. The NICE referral criteria only determine the scenarios where an urgent referral is required. Due to the increased discriminatory ability of the FIT for CRC, either the f-Hb concentration alone or a f-Hb based prediction model can allow to establish these three risk groups with different diagnostic strategies. As we have recently proposed, at least 90% of CRC should be detected in a high-risk group, requiring a fast-track referral to colonoscopy. In contrast, in a low-risk group, where no additional explorations are required, the probability of a missing CRC should be well below 1%, so that the risk of CRC is balanced with the risk of colonoscopy complications, mainly perforation [28].

Conclusions

To conclude, the discriminatory ability of any symptom based criteria is limited when compared with a f-Hb concentration based strategy. An urgent evaluation of the diagnostic accuracy of FIT in symptomatic patients attending primary care is required.

Abbreviations

AUC:

Area under the curve

CEA:

Carcinoembryonic antigen

CI:

Confidence interval

CRC:

Colorectal cancer

CRISP:

Colonoscopy Research into Symptom Prediction questionnaire

f-Hb:

faecal haemoglobin

FIT:

Faecal immunochemical test

LR:

Likelihood ratio

NICE:

National Institute for Health and Care Excellence

NPV:

Negative predictive value

OR:

Odds Ratio

PPV:

Positive predictive value

ROC:

Receiver-operating characteristic

SCL:

Significant colonic lesion

References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.

    Article  CAS  Google Scholar 

  2. Zauber AG, Knudsen AB, Rutter CM, Lansdorp-Vogelaar I, Savarino JE, van Ballegooijen M, Kuntz KM. Cost-Effectiveness of CT Colonography to Screen for Colorectal Cancer. Technol. Assess. Rep. 2009:1–92. https://www.ncbi.nlm.nih.gov/pubmed/25834880.

  3. NICE Clinical Guideline 27- Referral guidelines for suspected cancer. April 2011. www.nice.org.uk/CG027 [Internet]. 2011 [cited 2005 May 20]. Available from: www.nice.org.uk

  4. Mansouri D, McMillan DC, Crearie C, Morrison DS, Crighton EM, Horgan PG. Temporal trends in mode, site and stage of presentation with the introduction of colorectal cancer screening: a decade of experience from the west of Scotland. Br J Cancer. 2015;113:556–61.

    Article  CAS  Google Scholar 

  5. Ford AC. Veldhuyzen van Zanten SJO, Rodgers CC, Talley NJ, Vakil NB, Moayyedi P. diagnostic utility of alarm features for colorectal cancer: systematic review and meta-analysis. Gut. 2008;57:1545–53.

    Article  CAS  Google Scholar 

  6. Jellema P, van der Windt DA, Bruinvels DJ, Mallen CD, van Weyenberg SJ, Mulder CJ, et al. Value of symptoms and additional diagnostic tests for colorectal cancer in primary care: systematic review and meta-analysis. BMJ. 2010;340:c1269.

    Article  Google Scholar 

  7. Astin M, Griffin T, Neal RD, Rose P, Hamilton W. The diagnostic value of symptoms for colorectal cancer in primary care: a systematic review. Br J Gen Pract. 2011;61:e231–43.

    Article  Google Scholar 

  8. Cotterchio M, Manno M, Klar N, McLaughlin J, Gallinger S. Colorectal screening is associated with reduced colorectal cancer risk: a case-control study within the population-based Ontario familial colorectal cancer registry. Cancer Causes Control. 2005;16:865–75.

    Article  Google Scholar 

  9. Williams TGS, Cubiella J, Griffin SJ, Walter FM, Usher-Smith JA. Risk prediction models for colorectal cancer in people with symptoms: a systematic review. BMC Gastroenterol. 2016;16:63.

    Article  Google Scholar 

  10. Zafar A, Mak T, Whinnie S, Chapman MA. The 2-week wait referral system does not improve 5-year colorectal cancer survival. Colorectal Dis. 2012;14:e177–80.

    Article  CAS  Google Scholar 

  11. Rai S, Kelly MJ. Prioritization of colorectal referrals: a review of the 2-week wait referral system. Color Dis. 2007;9:195–202.

    Article  CAS  Google Scholar 

  12. Thorne K, Hutchings HA, Elwyn G. The effects of the Two-Week Rule on NHS colorectal cancer diagnostic services: a systematic literature review. BMC Health Serv Res. 2006;6:43.

    Article  Google Scholar 

  13. National Institute for Health and Clinical Excellence. Suspected cancer: recognitioin and referral [Internet]. NICE Guidel. 2017 [cited 2018 Mar 18]. Available from: https://www.nice.org.uk/guidance/ng12

  14. Oono Y, Iriguchi Y, Doi Y, Tomino Y, Kishi D, Oda J, et al. A retrospective study of immunochemical fecal occult blood testing for colorectal cancer detection. Clin. Chim. Acta. 2010;411:802–5.

    Article  CAS  Google Scholar 

  15. McDonald PJ, Digby J, Innes C, Strachan JA, Carey FA, Steele RJC, et al. Low faecal haemoglobin concentration potentially rules out significant colorectal disease. Colorectal Dis. [Internet]. 2013 [cited 2013 Jan 20];15:e151–e159.

    Article  CAS  Google Scholar 

  16. Cubiella J, Salve M, Díaz-Ondina M, Vega P, Alves MT, Iglesias F, et al. Diagnostic accuracy of the faecal immunochemical test for colorectal cancer in symptomatic patients: comparison with NICE and SIGN referral criteria. Color Dis. 2014;16:O273–82.

    Article  CAS  Google Scholar 

  17. Mowat C, Digby J, Strachan JA, Wilson R, Carey FA, Fraser CG, et al. Faecal haemoglobin and faecal calprotectin as indicators of bowel disease in patients presenting to primary care with bowel symptoms. Gut. 2016;65(9):1463–9.

    Article  Google Scholar 

  18. Rodríguez-Alonso L, Rodríguez-Moranta F, Ruiz-Cerulla A, Lobatón T, Arajol C, Binefa G, et al. An urgent referral strategy for symptomatic patients with suspected colorectal cancer based on a quantitative immunochemical faecal occult blood test. Dig Liver Dis. 2015;47:797–804.

    Article  Google Scholar 

  19. Godber IM, Todd LM, Fraser CG, MacDonald LR. Younes H ben. Use of a faecal immunochemical test for haemoglobin can aid in the investigation of patients with lower abdominal symptoms. Clin. Chem. Lab. Med. 2016;54:595–602.

    CAS  Google Scholar 

  20. Auge JM, Fraser CG, Rodriguez C, Lopez-Ceron M, Castells A, Roset A, et al. Clinical utility of one versus two faecal immunochemical test samples in the detection of advanced colorectal neoplasia in symptomatic patients. Clin Chem Lab Med. 2015;54:125–32.

    Google Scholar 

  21. Widlak MM, Thomas CL, Thomas MG, Tomkins C, Smith S, O’Connell N, et al. Diagnostic accuracy of faecal biomarkers in detecting colorectal cancer and adenoma in symptomatic patients. Aliment Pharmacol Ther. 2017;45:354–63.

    Article  CAS  Google Scholar 

  22. Westwood M, Lang S, Armstrong N, van Turenhout S, Cubiella J, Stirk L, et al. Faecal immunochemical tests (FIT) can help to rule out colorectal cancer in patients presenting in primary care with lower abdominal symptoms: a systematic review conducted to inform new NICE DG30 diagnostic guidance. BMC Med. 2017;15:189.

    Article  Google Scholar 

  23. Quantitative faecal immunochemical tests to guide referral for colorectal cancer in primary care [Internet]. [cited 2017 Mar 11]. Available from: https://www.nice.org.uk/guidance/dg30

  24. Quyn AJ, Steele RJ, Digby J, Strachan JA, Mowat C, McDonald PJ, et al. Application of NICE guideline NG12 to the initial assessment of patients with lower gastrointestinal symptoms: not FIT for purpose? Ann Clin Biochem. 2017;0:4563217707981.

    Google Scholar 

  25. Cubiella J, Vega P, Salve M, Díaz-Ondina M, Alves MT, Quintero E, et al. Development and external validation of a faecal immunochemical test-based prediction model for colorectal cancer detection in symptomatic patients. BMC Med. 2016;14:128.

    Article  Google Scholar 

  26. Cubiella J, Digby J, Rodríguez-Alonso L, Vega P, Salve M, Díaz-Ondina M, et al. The fecal hemoglobin concentration, age and sex test score: development and external validation of a simple prediction tool for colorectal cancer detection in symptomatic patients. Int. J. cancer [internet]. 2017;140:2201–2211.

    Article  CAS  Google Scholar 

  27. Adelstein B-A, Irwig L, Macaskill P, Katelaris PH, Jones DB, Bokey L. A self administered reliable questionnaire to assess lower bowel symptoms. BMC Gastroenterol. 2008;8:8.

    Article  Google Scholar 

  28. Rex DK, Schoenfeld PS, Cohen J, Pike IM, Adler DG, Fennerty MB, et al. Quality indicators for colonoscopy. Gastrointest Endosc. 2015;81:31–53.

    Article  Google Scholar 

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Meeting presentations

This research was partially presented in the XIX Reunión Nacional de la Asociación Española de Gastroenterologia held in Madrid 1-4th March, 2016.

Funding

This study was supported by a grant from Instituto de Salud Carlos III, Madrid, Spain (PI11/00094). Instituto de Salud Carlos III had no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the article for publication. JC has received an intensification grant through the European Commission funded “BIOCAPS” project (FP-7-REGPOT 2012–2013-1, Grant agreement no. FP7–316265).

Availability of data and materials

All data generated or analysed during this study are included in this published article and its supplementary information files.

Author information

Authors and Affiliations

Authors

Contributions

The authors’ contributions were as follows: JH and JC designed the analysis, PV, MS and LB collected the data, JH and JC performed the analysis and wrote the manuscript, and all the authors decided to submit the article for publication. All authors had full access to all of the data (including statistical reports and tables) in the study and can take responsibility for the integrity of the data and the accuracy of the data analysis. JC had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Joaquín Cubiella.

Ethics declarations

Ethics approval and consent to participate

Galician Clinical Research Ethics Committee approved this study (Code 2011/038) under resolution dated 2nd March 2011. We accessed patients’ clinical histories for study purposes in accordance with the research protocols laid down by clinical documentation departments. Patients provided written informed consent.

Consent for publication

Not applicable.

Competing interests

JC and MS had financial support from Instituto de Salud Carlos III for the submitted work but they had no financial relationships with any organisations that might have an interest in the submitted work in the previous five years, and no other relationships or activities that could appear to have influenced the submitted work. The remaining authors had no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous five years and no other relationships or activities that could appear to have influenced the submitted work.

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Herrero, JM., Vega, P., Salve, M. et al. Symptom or faecal immunochemical test based referral criteria for colorectal cancer detection in symptomatic patients: a diagnostic tests study. BMC Gastroenterol 18, 155 (2018). https://doi.org/10.1186/s12876-018-0887-7

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