Effect of Sex, Age, and Positivity Threshold on Fecal Immunochemical Test Accuracy: A Systematic Review and Meta-analysis

Selby, Kevin; Levine, Emma; Doan, Cecilia; Gies, Anton; Brenner, Hermann; Quesenberry, Charles; Lee, Jeffrey K.; Corley, Douglas A.

doi:10.1053/j.gastro.2019.08.023

Cited by 68 publications

(58 citation statements)

References 67 publications

(96 reference statements)

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“…Fecal immunochemical tests (FITs) for hemoglobin are widely used for colorectal cancer (CRC) screening [1][2][3]. FITs achieve overall high sensitivities for the detection of CRC, in the range of 70-80% at very high specificities of 90-95% [4][5][6]. Detection of advanced adenoma (AA), the most important precursor, and early-stage cancers is highly relevant for the reduction of CRC mortality [7,8].…”

Section: Introductionmentioning

confidence: 99%

Fecal Immunochemical Tests Detect Screening Participants with Multiple Advanced Adenomas Better than T1 Colorectal Cancers

Gies

Niedermaier

Gruner

et al. 2021

Cancers

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Background: Fecal immunochemical tests (FITs) are widely used for colorectal cancer (CRC) screening. The detection of early-stage cancer and advanced adenoma (AA), the most important premalignant lesion, is highly relevant to reducing CRC-related deaths. We aimed to assess sensitivity for the detection of CRC and AA stratified by tumor stage; number; size; histology of AA; and by location, age, sex, and body mass index (BMI). Methods: Participants of screening colonoscopy (n = 2043) and newly diagnosed CRC patients (n = 184) provided a stool sample before bowel preparation or CRC surgery. Fecal hemoglobin concentration was determined in parallel by nine different quantitative FITs among 94 CRC patients, 200 AA cases, and 300 participants free of advanced neoplasm. Sensitivities were calculated at original cutoffs and at adjusted cutoffs, yielding 93% specificity among all FITs. Results: At adjusted cutoffs, UICC stage I cancers yielded consistently lower sensitivities (range: 62–68%) compared to stage II–IV cancers (range: 73–89%). An even stronger gradient was observed according to T status, with substantially lower sensitivities for T1 (range: 39–57%) than for T2–T4 cancers (range: 71–100%). Sensitivities for the detection of participants with multiple AAs ranged from 55% to 64% and were by up to 25% points higher than sensitivities for T1 cancers. Conclusions: FITs detect stage I cancers and especially T1 cancers at substantially lower sensitivities than more advanced cancer stages. Participants with multiple AAs were detected with slightly lower sensitivities than stage I cancers and with even higher sensitivities than T1 cancers. Further research should focus on improving the detection of early-stage cancers.

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Section: Introductionmentioning

confidence: 99%

Fecal Immunochemical Tests Detect Screening Participants with Multiple Advanced Adenomas Better than T1 Colorectal Cancers

Gies

Niedermaier

Gruner

et al. 2021

Cancers

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“…Factors such as younger age [25][26][27] , female gender [26][27][28] , anaemia 10,20 , and degree of deprivation 29 might be associated with lower f-Hb among asymptomatic populations which could lead to higher false negative FIT results. There is limited evidence on whether these factors contribute to more false negative FIT tests among symptomatic patients, and NICE has highlighted the need for further research.…”

Section: Introductionmentioning

confidence: 99%

Quantitative faecal immunochemical test for patients with high risk bowel symptoms: a prospective cohort study

Laszlo

Seward

Ayling

et al. 2020

Preprint

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Objectives: To evaluate whether quantitative measurement of faecal haemoglobin (f-Hb) using faecal immunochemical testing (FIT) can be used to rule out colorectal cancer (CRC) for patients who present to primary care with high risk symptoms defined by national guidelines for urgent referral for suspected cancer (NICE NG12). Design: Prospective cohort study carried out between April 2017 and March 2019. Setting: 59 GP practices in London and 24 hospitals in England. Participants: Symptomatic patients in England referred to the urgent CRC pathway who provided a faecal sample for FIT in addition to standard investigations for cancer. Main outcome measures: CRC was confirmed by established clinical and histopathology procedures. f-Hb (microgr per gram of stool) was measured in a central laboratory blinded to cancer outcome. We calculated sensitivity (percentage of patients with CRC who have f-Hb exceeding specified cut-offs); false-positive rate [FPR] (percentage of patients without CRC whose f-Hb exceeds the same cut-offs); and positive predictive value [PPV] (percentage of all patients with f-Hb above the cut-offs who have CRC). Results: 4676 patients were recruited of whom 3596 patients were included (had a valid FIT test and a known definitive diagnosis). Among the 3596, median age was 67 years, 53% were female and 78% had colonoscopy. 90 patients were diagnosed with CRC, 7 with other cancers, and 3499 with no cancer found. f-Hb did not correlate with age, sex or ethnicity. Using f-Hb greater than or equal to 4 microgr/g (lowest limit of detection), sensitivity, FPR and PPV were 87.8%, 27.0% and 7.7% respectively. Using f-Hb greater than or equal to 10 microgr/g, the corresponding measures were 83.3%, 19.9% and 9.7%. 15 patients with CRC had f-Hb below 10 microgr/g. If FIT had been used at thresholds of 10 microg/gr or 4 microgr/g, 1 in 6 or 1 in 8 patients with cancer respectively would have been missed. If the absence of anaemia or abdominal pain is used alongside f-Hb 10 microgr/g, only 1 in 18 cancers would be missed but 56% of people without CRC could potentially avoid further investigations including colonoscopies. Conclusions: In our study, if FIT alone had been used to determine urgent referral for patients with high risk symptoms for definitive cancer investigation, some patients with bowel cancer would not have been diagnosed. If used in conjunction with clinical features, particularly in the absence of anaemia, the efficacy of FIT is significantly improved. With appropriate safety netting, FIT could be used to focus secondary care diagnostic capacity on patients most at risk of CRC.

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“…A recent meta-analysis of studies evaluating FIT performance in CRC screening concludes that the sensitivity and specificity of detection of neoplastic colonic lesions vary with positive cut-off values and suggests that the cut-off value could be reduced at centers with sufficient resources for colonoscopy follow-up. A 49% increase in positive tests and, therefore, follow-up colonoscopies would be achieved by using a cut-off value of <10 μg/g rather than <20 μg/g, compared to 146% using a cut-off value >10 and <20 μg/g rather than >20 μg/g, which are the references used in our study for symptomatic patients ( 25 ). We are aware that although the performance of FIT with a cut-off of 20 μg/g had optimal outcomes, 45 patients presented clinically significant pathology in the colonoscopy and were FIT negative (35 advanced adenoma, 3 cancer, 2 vascular lesion, and 5 inflammatory bowel disease cases).…”

Section: Discussionmentioning

confidence: 99%

Reducing the Cut-Off Value of the Fecal Immunochemical Test for Symptomatic Patients Does Not Improve Diagnostic Performance

Navarro¹,

Hijos²,

Sostres³

et al. 2020

Front. Med.

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Introduction: The fecal immunochemical test (FIT) has been established as a cost-effective test in colon cancer screening programmes. This test could also be helpful in symptomatic patients prior to colonoscopy, but data about diagnostic performance, and accurate cut-off values for these patients are still scarce. Materials and Methods: Prospective study that included consecutive unselected patients with gastrointestinal symptoms referred for colonoscopy between November 2016 and June 2018. We performed a FIT (FOB Gold ® test, cut-off 20 micrograms of Hb/gram of feces) prior to colonoscopy and determined the accuracy of FIT in terms of sensitivity, specificity, positive and negative predictive value for clinically significant pathology, advanced neoplasia, and colorectal cancer in symptomatic patients, using two different cut-off values. Results: A total of 727 patients (44.3% men, aged 58.5 ± 14.9 years) was included in the study. The main symptom was history of previous (non-active) rectal bleeding (34.7%), followed by diarrhea (15.0%). Over one quarter of the patients (25.9%) had a positive FIT result. The caecal intubation rate was 95.5%. Clinically significant pathology was identified in 142 colonoscopies (19.5%), advanced neoplasia in 115 (15.8%) and colorectal cancer in 36 colonoscopies (5.0%). FIT performed very well for clinically significant pathology, advanced neoplasia and cancer, with a high negative predictive value (NPV). Reducing the cut-off value to 10 μg/g yielded similar NPV results, with a decrease in specificity. Using a combination of symptoms with a positive FIT result did not improve FIT performance. Only specificity was slightly higher compared to FIT alone, but this was paralleled by a decrease in sensitivity and NPV for cancer and clinically significant pathology. The odds of presenting clinically significant pathology, advanced neoplasia, or cancer increased with FIT concentration. Conclusions: The specificity and NPV of FIT for clinically significant pathology, advanced neoplasia, and cancer are high in symptomatic patients. FIT is a helpful test for determining the need to perform further studies. It may not be necessary to reduce the cut-off value for symptomatic patients, since FIT performance with the current standard cut-off value used in colorectal cancer screening was accurate. FIT can be used to avoid or prioritize colonoscopy procedures.

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Effect of Sex, Age, and Positivity Threshold on Fecal Immunochemical Test Accuracy: A Systematic Review and Meta-analysis

Cited by 68 publications

References 67 publications

Fecal Immunochemical Tests Detect Screening Participants with Multiple Advanced Adenomas Better than T1 Colorectal Cancers

Fecal Immunochemical Tests Detect Screening Participants with Multiple Advanced Adenomas Better than T1 Colorectal Cancers

Quantitative faecal immunochemical test for patients with high risk bowel symptoms: a prospective cohort study

Reducing the Cut-Off Value of the Fecal Immunochemical Test for Symptomatic Patients Does Not Improve Diagnostic Performance

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