Indication - Cancer
Faecal immunochemical test (FIT)
Latex agglutination immuno-turbidimetry
First added in 2019
Changed in 2020
To screen for colorectal cancer
WHO prequalified or recommended products
WHO supporting documents
WHO priority medical devices for cancer management https://apps.who.int/iris/handle/10665/255262; Colorectal cancer screening. IARC handbooks of cancer prevention, volume 17 https://publications.iarc.fr/Book-And-Report-Series/Iarc-Handbooks-Of-Cancer-Prevention/Colorectal-Cancer-Screening-2019
ICD11 code: 2B91.Z
Summary of evidence evaluation
The evidence for the impact on mortality of FIT testing in colon cancer screening programmes is derived from observational studies (8) and not RCTs. Primary studies of the accuracy of FIT as compared to gFOBT, however, indicate equivalent or better accuracy, although no systematic review of these studies has been published.
Summary of SAGE IVD deliberations
Given the strong evidence from RCTs of the benefits of gFOBT in screening programmes and the emerging evidence of the benefits of FIT over gFOBT, the Group considered that the evidence is strong enough to include FIT on the EDL.
SAGE IVD recommendation
SAGE IVD recommended addition of FIT to the EDL, noting the strong evidence that it clinically supports diagnosis, resulting in reduced mortality from colorectal cancer. It is important that the systematic review of studies comparing FIT with gFOBT be completed and published.
Details of submission from 2020
Disease condition and impact on patients: Colorectal cancer is the fourth most common cancer worldwide and the third most common cause of death, with 1.8 million and 880 000 new cases, in 2018 (1, 2). Does the test meet a medical need? About one in three middle-income countries and two of three low-income countries do not have basic diagnostic capacity for cancer. It is estimated that 5–30% of cancer cases are not diagnosed because of lack of diagnostic capacity. These significant testing gaps have major public health consequences. How this test is used: FIT is generally considered easy to use, and Cancer Care Ontario reported that the newly designed collection device reduces the contact people have with their stool when collecting it, increasing the acceptability (3).
Public health relevance
Prevalence: Colorectal cancer is the fourth most common cancer worldwide and the third most common cause of death, with 1.8 million and 880 000 new cases, in 2018 (1, 2). Socioeconomic impact: A “mandate of acceptability” has been launched to acknowledge the importance of easy-to-use, “wordless” devices for rural, vulnerable and disadvantaged populations (4–6).
WHO or other clinical guidelines relevant to the test
WHO recommends use of FIT for early detection of colorectal cancer in screening programmes (7). IARC has endorsed the use of stool-based tests for population screening of colorectal cancer on the basis of systematic reviews of the literature (8).
Evidence for clinical usefulness and impact
FIT is essential for early detection of colorectal cancer in screening programmes (7). Use of FIT for colorectal cancer screening is associated with a reduction in cancer-related mortality of 10–40% (2). In a large population-based study in Taiwan (China), 1 160 895 people aged 50–69 years were screened with one to three rounds of FIT and compared with an unscreened group. After a maximum follow-up of 6 years, a 10% decrease in colorectal cancer mortality was seen in the screened population (9). A study in Italy showed a 10% decrease in cumulative incidence and a 27% decrease in mortality (10). Extrapolation from a modelling analysis showed that the number of life-years gained with use of FIT was comparable to that with colonoscopy every 10 years (11).
Evidence for economic impact and/or cost–effectiveness
An IARC working group compared guaiac- and FIT-based screening programmes and found various levels of potential harm and benefit (8). All the tests for occult blood in stool increased QALYs as compared with no screening. The more sensitive tests are more expensive. Smith et al. (12) analysed the cost– effectiveness of management of a screening programme, identifying patients, FIT kits and their processing and diagnostic colonoscopy after a positive FIT. The cost per person was US$ 33–92, whereas the cost–effectiveness for an additional advanced neoplasia detected was US$ 11 198–28 389. The number of cancers avoided per 1000 screens was estimated to be 1.46–4.86. In a microsimulation model, Lansdorp-Vogelaar et al. (13) showed that biennial FIT screening of people aged 55–75 years provided 84.9 life-years gained at a cost of US $137 000 per 1000 participants, which was considered to be cost–effective as compared with no screening. Screening for colorectal cancer with FIT, gFOBT or colonoscopy resulted in a return on investment. The FIT system is automated and does not require highly skilled laboratory operators or special training, and the samples can be collected by patients at home. Education for sample collection is the responsibility of general practitioners as part of awareness of early diagnosis of cancer. A FIT programme must, however, be part a wider programme of screening for colorectal cancer, including estimates of the workforce (gastroenterologists) and devices (colonoscopes) necessary for secondary and tertiary care and an appropriate oncology surgery service integrated into a multidisciplinary environment. FIT screening can be managed in primary care settings, the general practitioner informing and referring patients screened as positive for endoscopic assessment of the causes of occult bleeding, tracking the results and informing patients about subsequent diagnostic and therapeutic steps. Post-test counselling by a general practitioner is important to ensure adherence to the follow-up diagnosis and treatment.
Ethical issues, equity and human rights issues
Consent is required to obtain a faecal sample. FIT has been denoted by WHO as a priority medical device for cancer management (7) as a diagnostic and screening test for occult gastrointestinal causes of bleeding, including colorectal cancer and curable pre-cancerous conditions such as polyps. Ensuring access as part of UHC is an ethical issue. In a screening programme for colorectal cancer based on FIT, a referral pathway must be ensured for high-risk patients who screen positive to ascertain the nature of the disease, rapidly resect any cancer or pre-cancerous lesion and prevent malignant transformation of high-risk colorectal adenomas. The acceptability of the test has been acknowledged to ensure comprehension by the entire population, including low-literacy and tribal groups, and acceptance of a colorectal cancer diagnosis. Easy-to-deliver screening methods generally reach a large proportion of the population at primary care level.
1. Cancer tomorrow. Lyon: International Agency for Research on Cancer; 2019 (http://gco.iarc.fr/ tomorrow/home, accessed May 2019). 2. Cancer key facts. Geneva: World Health organization; 2018 (http://www.who.int/news-room/fact- sheets/detail/cancer, accessed May 2019). 3. Transition to fecal immunochemical testing (FIT). Frequently asked questions for primary care providers. Toronto: Cancer Care Ontario; 2017 (https://archive.cancercare.on.ca/common/pages/ UserFile.aspx?fileId=381441, accessed April 2019). 4. Allison JE, Fraser CG, Halloran SP, Young GP. Population screening for colorectal cancer means getting FIT: the past, present, and future of colorectal cancer screening using the fecal immunochemical test for hemoglobin (FIT). Gut Liver. 2014;8(2):117–30. 5. Pham R, Cross S, Fernandez B, Corson K, Dillon K, Yackley C, et al. “Finding the right FIT”: rural patient preferences for fecal immunochemical test (FIT) characteristics. J Am Board Fam Med. 2017;30(5):632–44. 6. Coronado GD Sanchez J, Petrik A, Kapka T, DeVoe J, Green B. Advantages of wordless instructions on how to complete a fecal immunochemical test: lessons from patient advisory council members of a federally qualified health center. J Canc Educ. 2013;29(1):86–90. 7. WHO list of priority medical devices for cancer management (WHO medical device technical series). Geneva: World Health Organization; 2017 (http://www.who.int/medical_devices/ publications/priority_med_dev_cancer_management/en/, accessed April 2019). 8. Lauby-Secretan B, Vilahur N, Bianchini F, Guha N, Straif K for the International Agency for Research on Cancer Handbook Working Group. The IARC perspective on colorectal cancer screening. N England J Med. 2018;378:1734–40. 9. Chiu HM, Chen SL, Yen AM, Chiu SY, Fann JC, Lee YC, et al. Effectiveness of fecal immunochemical testing in reducing colorectal cancer mortality from the One Million Taiwanese Screening Program. Cancer. 2015;121:3221–9. 10. Giorgi Rossi P, Vicentini M, Sacchettini C, Di Felice E, Caroli S, Ferrari F, et al. Impact of screening program on incidence of colorectal cancer: a cohort study in Italy. Am J Gastroenterol. 2015;110(9):1359–66. 11. Zauber AG, Lansdorp-Vogelaar I, Knudsen L, Wilschut J, van Ballegooijen M, Kuntz KM. Evaluating test strategies for colorectal cancer screening: a decision analysis for the US Preventive Services Task Force. Ann Intern Med. 2008;149:659–69. 12. Smith DH, O’Keeffe Rosetti M, Mosen DM, Rosales AG, Keast E, Perrin N, et al. Balancing adherence and expense: the cost–effectiveness of two-sample vs one-sample fecal immunochemical test. Popul Health Manag. 2019;22(1):83–9. 13. Lansdorp-Vogelaar I, Goede SL, Bosch LJW, Melotte V, Carvalho B, van Engeland M, et al. Cost- effectiveness of high-performance biomarker tests vs fecal immunochemical test for noninvasive colorectal cancer screening. Clin Gastroenterol Hepatol. 2018;16(4):504–12