Sensitivity was particularly low for T1 and stage I cancers in the distal colon (32% and 52%, respectively) although generally very high for cancers with higher T stage (T2-T4) and more advanced stage (UICC stage IIIV) overall. We pooled results from 5 studies that were deemed at low risk of bias. We deemed all 4 studies employing qualitative FITs28,30,32,37 and all 3 studies using delayed colonoscopy as a reference standard26,34,37 as high risk. Grading quality of evidence and strength of recommendations in clinical practice guidelines: part 3 of 3. the GRADE approach to developing recommendations. Heterogeneity and wide confidence intervals limit the trustworthiness of our findings. The FIT identified patients with CRC with overall high sensitivity but missed nearly 50% of small (T1) and 32% of UICC stage I CRCs. In 3 relevant studies, sensitivity for CRC varied from 67% to 100% and specificity from 83% to 95%. How Fit Is FIT for Detecting Colorectal Cancer? independently extracted data from each included study, using Systematic Review Data Repository.13 For studies presenting results for multiple FIT thresholds, we extracted all data to maximize the yield of information. Data extraction and quality assessment were conducted in duplicate. I asked what did it show, because they test for 11 different cancers or categories. Gimeno-Garcia To fully evaluate FIT sensitivity and effectiveness, a longitudinal study should assess its performance over several rounds of testing, taking into account the stage and site distribution of screen-detected CRCs and [interval CRCs] ICs in each round, they suggested. Such a strategy is associated with higher cost, lower adherence, and higher risk for rare, but serious, complications.2-6. Fecal immunochemical test (FIT). AW, Westwood Our search identified 3026 records (Figure 1). Stool DNA testing. The FIT identified patients with CRC with overall high sensitivity but missed nearly 50% of small (T1) and 32% of UICC stage I CRCs. In the study, Imperiale and his colleagues determined that when the FIT was set to be more sensitive, the test caught 95 percent of cancers, but resulted in 10 percent false positives. Specifically, the investigators wanted to see if a colonoscopy identified any cancer missed by the FIT. et al; QUADAS-2 Group. We explored the robustness of our results in a post hoc sensitivity analysis including only studies in patients with family history of CRC that used quantitative FIT with a cut-off value of less than 25 g Hb/g feces. Sensitivity was particularly low for T1 and stage I cancers in the distal colon (32% and 52%, respectively) although generally very high for cancers with higher T stage (T2-T4) and more advanced stage (UICC stage . et al; EPICOLON Group. A, Jimnez-Sosa The use of FIT in symptomatic patients is associated with a better prognosis in CRC. The study should also evaluate the location and detection rate of advanced adenomas and quantitative fecal hemoglobin results during the rounds of testing. All Rights Reserved, Challenges in Clinical Electrocardiography, Clinical Implications of Basic Neuroscience, Health Care Economics, Insurance, Payment, Scientific Discovery and the Future of Medicine, 2017;177(8):1110-1118. doi:10.1001/jamainternmed.2017.2309. Cologuard is one of six approved methods for colon cancer screening in the United States, including one of three stool-based tests. Amersi S, Vilkin This test is able to look for a specific type of blood in your stool which helps identify if . independently extracted data and evaluated study quality using the Quality Assessment of Diagnostic Accuracy Studies2 tool, and evaluated the quality of the body of evidence by means of GRADE (Grading of Recommendations Assessment, Development, and Evaluation). However, recommendations for increased-risk individuals are more aggressive and support only use of colonoscopy. Used not only as a screening test, colonoscopies are also used as a diagnostic procedure to follow up after positive results from a fecal occult blood test (FOBT) or fecal immunochemical test (FIT), fecal DNA test, sigmoidoscopy . GRADE handbook for grading quality of evidence and strength of recommendations. Colonoscopy-controlled intra-individual comparisons to screen relevant neoplasia: faecal immunochemical test vs. guaiac-based faecal occult blood test. Because the fecal occult blood test (FOBT) was not as accurate, the fecal immunochemical test (FIT) was developed. Chemical and immunological testing for faecal occult blood in screening subjects at risk of familial colorectal cancer. de Wijkerslooth Terms of Use| We explored the diagnostic accuracy at 3 different FIT thresholds (<15 g Hb/g, 15 to 25 g Hb/g, >25 g Hb/g feces) based on existing practice and to maximize sensitivity for an increased-risk population. JD, Armitage et al. Several limitations have to be acknowledged about the evidence and the review itself. L, After deduplication, we screened 2154 titles and abstracts and rejected 1952 records as noneligible. However, the validity of our conclusions is undermined by low or very low quality of the body of evidence. E, Nicols-Prez Quiz Ref IDUse of cutoff values between 15 to 25 g Hb/g feces had the best combination of sensitivity and specificity for the diagnosis of CRC (93% and 94%, respectively), as well as the highest LR+ (15.1) and lowest LR (0.07). They followed these individuals under four endpoints: initial colonoscopy, health plan disenrollment, death, or December 31, 2015, comparing them against a non-CRC control group. A, Results were at least as good as from previous systematic reviews focusing n average-risk individuals.10,11,38 To ensure internal validity of our conclusions, we implemented current guidelines for the conduct and reporting of systematic reviews12,39 and used a prespecified protocol. MEDLINE, EMBASE, Cochrane Library, and gray literature sources through August 2016. Sensitivity 98%; . Critical revision of the manuscript for important intellectual content: All authors. Surveillance after polypectomy and after resection of colorectal cancer. Seven studies were deemed at high or unclear risk of bias. Overall quality was deemed very low, low, moderate, or high using GRADEpro version 3.6 (GRADEpro GDT). In our main analysis, for studies presenting results at multiple FIT thresholds, we used data for the lowest cutoff and the minimum number of samples available. Fecal occult blood test: The fecal occult blood test (FOBT) is a lab test used to check stool samples for hidden (occult) blood. Equivalency of fecal immunochemical tests and colonoscopy in familial colorectal cancer screening. However, those who did not get a follow-up colonoscopy were about twice as likely to die of colorectal cancer over a 10-year period as those who did have a follow-up colonoscopy. and percentage of males ranged from 30.2 to 50.6%. FIT is currently FDA-approved for spontaneous stool and DRE, however, samples are not commonly obtained by DRE. It is a very sensitive test, and that polyps, hemorrhoids (both internal and external), and ulcers can all cause a positive fit test. MH, Hardcastle JS, Van Der Hulst A proposal to standardize reporting units for fecal immunochemical tests for hemoglobin. In a study from the Netherlands, 4523 people (age range, 50-74) underwent FIT screening with OC-Sensor Micro; a hemoglobin concentration of 50 ng/mL was considered positive. FIT (Fecal Immunochemical Test) is a stool test used to look for possible signs of colorectal cancer. S, Levin The Cologuard test has a 12% false-positive rate, which means 1 in 10 positive tests will incorrectly identify cancer or polyps. Complications of colonoscopy. The rate increased with age, but the rates found at all ages are much lower than rates of cancer in people undergoing screening colonoscopy without a prior FIT, lead authors George F. Longstreth, MD, and Daniel S. Anderson, MD, FACP, of Kaiser Permanente, Southern California, San Diego, told CLN Stat in a statement. The test looks for tiny traces of blood in the stool, a way of screening people for colon cancer. Sample size of studies ranged from 116 to 1041 patients. A sensitivity analysis excluding studies at high or unclear risk of bias verified robustness of our conclusions. Fecal immunochemical test (FIT). Finally, we checked reference lists of primary studies included, relevant systematic reviews and meta-analyses, and pertinent guidelines. and P.P.) Quantitative and 1-sample FIT showed adequate test performance, but data on other FIT brands and multiple samples were insufficient. et al; GRADE Working Group. Three-year survival was greater in the CRC group diagnosed after a positive FIT (72% vs 59%). LG, van Rijn Z, Rozen Finally, we graded the quality of the body of evidence using appropriate methodology (GRADE). HermannBrenner,MD, MPH; SilviaCalderazzo,PhD; ThomasSeufferlein,MD; LeopoldLudwig,MD; NektariosDikopoulos,MD; JrgMangold,MD; WolfgangBck,MD; ThomasStolz,MD; ThomasEisenbach,MD; ThomasBlock,MD; AnnetteKopp-Schneider,PhD; DavidCzock,MD; KajaTikk,PhD, Fecal Immunochemical Tests in Patients at Increased Risk for CRC, Assessment of Quality of Body of Evidence, Get the latest from JAMA Internal Medicine, To register for email alerts, access free PDF, and more, Get unlimited access and a printable PDF ($40.00), 2023 American Medical Association. Cologuard found 93 percent of the cancers detected by screening colonoscopy. Also, there are no diet or drug restrictions. PM, Reitsma This research provides additional valuable information to the body of high-quality comparative evidence about the diagnostic accuracy of FIT screening compared with other fecal tests or colonoscopy, Carlo Senore, MD, and Manuel Zorzi, MD, wrote in a related editorial. and P.P.) On the other hand, our results also show that FIT could diagnose only half of the cases with AN. This test examines DNA in your stool for evidence of cells shed by colorectal cancer. Colorectal cancer: epidemiology, risk factors, and health services. 20 participants of the 47 who had polyps had advanced adenomas . This follow-up rate is comparable to some of the best follow-up rates in the United States and elsewhere, Dr. Corley said. CR, Two authors (A.K. Data Sources Medicines and foods do not interfere with the test. 1 In order to reduce mortality and incidence of CRC, the National Health Service Bowel Cancer Screening Programme (NHS BCSP) in . Many successful colorectal cancer screening programs, including those in the United States, use some combination of stool-based tests, such as FIT, and screening colonoscopy, Dr. Corley said, so the new study results are very relevant to settings in the United States.. Customize your JAMA Network experience by selecting one or more topics from the list below. Further research is needed to assess whether this relationship . MR, Seaman Understanding why some people are willing to be screened but do not follow up can lead to improvements in the effectiveness of the screening process.. et al; American Cancer Society Colorectal Cancer Advisory Group; US Multi-Society Task Force; American College of Radiology Colon Cancer Committee. Stool samples collected at home are sent in for analysis. For the study, Manuel Zorzi, M.D., M.Sc., of the Veneto Tumour Registry in Padua, Italy, and his colleagues, examined the medical records of participants in a regional colorectal screening program who took a FIT test between January 1, 2004, and September 30, 2017. I'm reading theres a 13 percent chance of false positive. L, Rodriguez-Berrocal and P.P.) Another study examined the merits of colonoscopy in patients with negative FIT tests in a large program that conducted annual screening. Whiting et al; Standards of Practice Committee, American Society for Gastrointestinal Endoscopy. The test, known as the fecal immunochemical test (FIT), checks for traces of blood in patient-collected stool samples, which can be an early . Diagnostic Accuracy of Fecal Immunochemical Test in Patients at Increased Risk for Colorectal Cancer: A Meta-analysis. Diagnostic yield of the immunochemical fecal occult blood test in asymptomatic first degree relatives of colorectal cancer patients. SP, Young The potential role of the fecal immunochemical test (FIT) for screening patients at increased risk for colorectal cancer (CRC) has not yet been elucidated. We included 12 studies (6204 participants). Both studies appear in the Clinical Gastroenterology and Hepatology journal. Can Cologuard detect cancer? Hierarchical summary receiver operating curve (HSROC) plot of sensitivity versus specificity for performance of FIT in studies using quantitative FIT with cut off value less than 25g/g only in patients with familial risk of CRC, eTable 1. Screening colonoscopy was better at finding cancer and pre-cancerous polyps than both Cologuard and the FIT test. In a pragmatic trial34 assessing the effectiveness of a diagnostic strategy using annual FIT for 3 years for detection of AN vs colonoscopy in asymptomatic patients with a family history of CRC, annual FIT was as good as colonoscopy for AN; however, it missed almost 40% of advanced adenomas. Y, Liu U. Oort LG, van Rijn AZ, // The researchers identified 268 cases of CRC from a database search of 96,804 subjects ages 5075 years with initial negative FIT results. 2017;177(8):11101118. et al; EPAGE II Study Group. Fecal DNA testing was 92% sensitive and 87% specific, whereas FIT was 74% sensitive and 95% specific. independently evaluated the quality of included studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool.15 Discrepancies were resolved by consensus. Lin FA, Screening for colorectal cancer, the second leading cause of cancer-related deaths in the United States and other high-income countries, has been shown to reduce deaths from this disease. In recent years fecal immunochemical tests (FITs) have been offered as a primary screening test for colorectal cancer (CRC) in a growing number of countries. In this cohort, the overall rate of cancer was 1.4 per 1,000. The diagnostic odds ratio (DOR) for diagnosis of CRC and AN was 129 (95% CI, 11-1579) and 11 (95% CI, 8-17), respectively. van Rossum The Bayesian estimate from the positive test result is almost seven times the assumed 0.7% prevalence. The new faecal immunochemical test (FIT) is due to be introduced into the bowel cancer screening programme (BCSP) in England later this year to replace the current test. We synthesized existing data using hierarchical models to account for the correlation between sensitivity and specificity. Advanced colonic neoplasia in the first degree relatives of colon cancer patients: A colonoscopy-based study. PM, Zwinderman AACC uses cookies to ensure the best website experience. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. Low sensitivity of FIT for early-stage CRC underlines the need for research on potential improvements in FIT-based CRC screening. Positive and negative predictive values were 7.7% and 99.9%, respectively. JJ, Burnand The initial sharp rise was expected, the researchers noted, due to colorectal cancer being found during follow-up colonoscopy. GM, Baron L, Gorber Male sex (OR = 1.30, 95%CI 1.03, 1.62), age 65 years (OR = 1.27, 95%CI 1.01, . Appropriateness of colonoscopy in Europe (EPAGE II). FIT costs about $20 or less and is covered by Medicare and most health insurance plans. EM, FJ, The DNA test is 92% effective at detecting cancers. KG. CLN Stat Quiz Ref IDThe type of FIT used and cutoff threshold were the most important contributors to the heterogeneity of results. FIT is the dominant screening test for colorectal cancer in most economically advanced countries, and the results support the accuracy of widespread periodic FIT screening, they added. JL, Akl Tumors were stratified by location. Continuing without changing cookie settings assumes you consent to our use of cookies on this device. 2023 American Medical Association. TR, de Haan A positive FIT can also be due to a polyp, a pre . Thus, our results suggest that in increased-risk individuals FIT has high diagnostic accuracy for CRC. et al. Previous Presentation: This study was presented as an abstract at the 24th United European Gastroenterology Week; October 18, 2016; Vienna, Austria. False positives and false negatives do happen in Cologuard tests. by Elia Ben-Ari, December 22, 2022, 95 percent CI 5.1-9.3 percent predicts FIT will be positive in this low-risk symptomatic group, whereas 99.8 per cent CI 99.5-99.9 per cent predicts FIT would be negative. Privacy Policy| Rutter Individuals at average risk are screened using the fecal immunochemical test (FIT), which has been available in British Columbia for the past 5 years This points to one possible reason why people in this group, on average, were less likely to get follow-up colonoscopy exams, Dr. Corley said. BA, Sylvester RJ, et al. Having bowel cancer screening reduces your risk of dying from bowel cancer by at least 25% [footnote 1]. Carroll It tests for hidden blood in the stool, which can be an early sign of cancer. If cancer is detected, treatment is usually the next step. et al. In 3 studies, individuals with positive FIT results underwent immediate colonoscopy, whereas individuals with negative FIT results underwent delayed colonoscopy, introducing potential differential verification bias.26,34,37 Moreover, 3 studies used an unacceptable interval (>3 months) between FIT and reference standard,26,34,37 while 2 studies provided no relevant details.30,36 In the rest of the studies, the interval between FIT and reference standard was less than 1 month in 5 studies27,29,31,33,35 and 2 months in 1 study.28. Source: CLN Stat. M, Ko While this is a relatively small percentage, it is important to note that a positive fit test result can be an indicator of cancer and should be taken seriously. The test should be done yearly. (DNA tests, however, do return more . J, Altman We assessed the stability of our findings in a series of sensitivity analyses (eTable 1 in the Supplement). One study we published showed that by increasing screening rates from 40% to 80%, we could cut the incidence of colorectal cancer deaths in half, he said. Inc32,37; OC-light, Eiken Chemical28; and HemeSelect, Smith-Kline Diagnostics30). Higgins Recommendations on screening for colorectal cancer in primary care. Lastly, she said that 3 out of four people have polyps, hemorrhoids, ulcers, or a combination of the three. et al. As patients with an abnormal result are at greater risk for precancerous polyps or cancer, it is important to attend to follow-up procedures. There are two types of stool tests for colon cancer. P, DG; PRISMA Group. Based on GRADE summaries (eTable 2 in the Supplement) we deemed the quality of the evidence to be low or very low. Importance We fitted hierarchical logistic regression models when 4 or more studies were available.21-24. Seven studies were deemed at high or unclear risk of bias. AH. All studies assessed the accuracy of FIT for AN,26-37 but only 7 studies (4790 patients) reported data specifically for CRC.27,29,31-35 Prevalence of AN ranged between 3.2% and 14.5% and between 0.6% and 2.1% for CRC. 1, 6, 8 With single-vial screening adopted as the standard method of FIT testing, the St. By continuing to use our site, or clicking "Continue," you are agreeing to our, Figure 2. Fortunately, with routine screening . Otero-Estevez The most common types of cancer that lead to positive fit test results include colorectal, breast, and lung cancers. Clinical literature and commentary point to a new protocol for evaluating fecal immunochemical testing (FIT) and how well this modality flags colorectal cancer (CRC). Fraser It is also important to establish optimal thresholds, test cutoff values, and number and frequency of FIT samples.10 Our results also should prompt randomized trials to assess the implementation of FIT either alone or in combination with other screening procedures into screening strategies for increased-risk individuals. ME, Levi The average sensitivity of FIT for CRC was 93% (95% CI, 53%-99%), and the average specificity was 91% (95% CI, 89%-92%), yielding a positive likelihood ratio (LR+) of 10.30 (CI 7.7-13.9) and a negative likelihood ratio (LR) of 0.08 (95% CI, 0.01-0.75) (GRADE: very low). et al. Can have false-positive test results. Reitsma et al. Statistical analysis: Katsoula, Paschos, Haidich, Tsapas. JA, Eisen Annual fecal immunochemical testing (FIT) is cost-effective for colorectal cancer (CRC) screening. TR, A positive FIT test is concerning. Over that time, about 2 percent of the people, about 2,700 of them, had positive tests. Main Outcomes and Measures Moreover, we conducted a sensitivity analysis excluding studies that used delayed colonoscopy as the reference standard. Can patients at high risk for significant colorectal neoplasms and having normal quantitative faecal occult blood test postpone elective colonoscopy? Systematic Review Data Repository. PF, Rutjes In June, the U.S. Preventive Services Task . DG. SP. Sensitivity Estimates of Colorectal Cancer and Advanced Neoplasia, Table 1. The new study, published in Alimentary Pharmacology & Therapeutics, concluded that a positive test of ten micrograms or more of haemoglobin per gram of sample detects 91% of underlying cancers. JE, Halloran et al; US Preventive Services Task Force.