Alfresa Pharma Corporation

Fecal Immunochemical Test

Key Things About Fecal Immunochemical Test (FIT)

In tests used for the early detection of colorectal cancer, the fecal immunochemical test (FIT), which is a fecal occult blood test performed using an immunological method, has been shown to be highly useful.1-2) Our products enable quantitative assays of fecal transferrin in addition to the FIT (fecal hemoglobin), and the primary screening can be performed non-invasively and rapidly by colonoscopy.

FIT for Colorectal Cancer Screening

The fecal occult blood test (FOBT) has been shown to be useful for the screening of colorectal cancer (CRC).1-2) A case-control study performed in Japan showed that annual screening using the one-day method reduces CRC mortality by 60%.3-4) Since the two-day method (a method where stool samples are collected for 2 days, and the result is considered positive if any of the sample is positive) is more sensitive than the one-day method,5-6) particularly for the detection of early-stage colorectal cancer,5) the former method is currently used widely in Japan.3)
The FOBT is classified into 2 types, FIT and guaiac-based FOBT (gFOBT); the FIT is more sensitive, specific, and accurate than gFOBT in detecting intestinal bleeding.7) In addition, our FIT products employ a quantitative method, and the cut-off value that serves as the basis for assessment can be set arbitrarily. The number of false-positive and false-negative cases can be adjusted by setting the cut-off value arbitrarily, which enables adjustment of the positive rate according to the capacity of each institution for processing detailed examinations.

Effectiveness of arbitrarily setting the optimal cut-off value

Purposes (e.g.) Cut-off value Effects8) Advantages and disadvantages
  • Population-based screening
    (organized screening)
Set high
  • The positive rate decreases
  • Sensitivity decreases but specificity increases
  • Thus, false positives decrease and false negatives increase
  • Selective detection of patients at a high risk is feasible, and the number of cases receiving subsequent detailed examinations can be controlled.
  • The overall cost of screening, including the cost of detailed examination, can be adjusted based on the budget.9)
  • Opportunistic screening
  • Private medical checkup
 Set low
  • The positive rate increases
  • Sensitivity increases but specificity decreases
  • Thus, false negatives decrease and false positives increase
  • The number of overlooked cases can be controlled. For patients who undergo cancer screening at their own expense, minimizing overlooked cancers is more important than the burden of expenses and the pain associated with secondary detailed examination.
  • It may overwhelm the capacity for processing detailed examinations.

FIT for Symptomatic Patients

FIT can be useful not only for CRC screening but also for diagnosing/assessing CRC.10) Additionally, the National Institute for Health and Care Excellence (NICE) guideline [NG12] states that patients who do not have rectal bleeding and meet certain criteria should be offered the FIT quantitative assay to assess their risk of colorectal cancer.10)

References

  • 1）Rex DK, et al. Colorectal Cancer Screening: Recommendations for Physicians and Patients from the U.S. Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2017; 112: 1016-1030.
  • 2）Canadian Task Force on Preventive Health Care. Recommendations on screening for colorectal cancer in primary care. CMAJ. 2016; 188: 340-348.
  • 3）Guidelines for colorectal cancer screening based on efficacy evaluation (Ministry of Health, Labour and Welfare Cancer Research Grant 2004, “Research Group on Establishment of Appropriate Methods and Evaluation Methods for Cancer Screening,” March 24, 2005). Available from: http://canscreen.ncc.go.jp/guideline/daicyougan.html [Article in Japanese]
  • 4）Saito H, et al. A case-control study evaluating occult blood screening for colorectal cancer with hemoccult test and an immunochemical hemagglutination test. Oncol Rep. 2000; 7: 815-819.
  • 5）Hisamichi S, et al. Tsubono Y. Mass screening for colorectal cancer in Japan. Cancer Detect Prev. 1991;15(5):351-6.
  • 6）Iwase T. The evaluation of an immunochemical occult blood test by reversed passive hemagglutination compared with Hemoccult II in screening for colorectal. Fecal Occult Blood Tests: Current Issues and New Tests. 1992: 90-5.
  • 7）Borges LV, et al. Fecal occult blood: a comparison of chemical and immunochemical tests. Arq Gastroenterol. 2018;55:128-132.
  • 8）Miyake, K. Significance of reference value and cut-off value in clinical laboratory tests. Nihon Naika Gakkai Zasshi. 2005; 94: 2467-2472. [Article in Japanese]
  • 9）IARC (2019). Colorectal cancer screening. IARC Handb Cancer Prev. 17:1 -300. Available from: http://publications.iarc.fr/573
  • 10）National Institute for Health and Care Excellence NICE Guideline 12. Suspected cancer: Recognition and referral. 2021. Available from: https://www.nice.org.uk/guidance/ng12

Key Things About Colorectal Cancer (CRC)
[Importance of early detection to reduce cancer mortality]

Cancer is the leading cause of death among people under the age of 70 in many countries in North America, South America, Europe, Asia and Oceania. Among the various cancers, colorectal cancer (CRC, including colon and rectum cancer) is the third leading cause of new cases and the second leading cause of death in the world.1) In Japan, CRC is the leading cause of death among females and the second leading cause of death among males.2)

Number of deaths by cancer type (total of both sexes, 2020)3)

1st 2nd 3rd 4th 5th
Wordwide Lung Colon/rectum Liver Stomach Breast
Latin America and the Caribbean Lung Colon/rectum Breast Prostate Stomach
Northern America Lung Colon/rectum Pancreas Breast Prostate
Asia Lung Liver Stomach Colon/rectum Oesophagus
Europe Lung Colon/rectum Breast Pancreas Prostate
Oceania Lung Colon/rectum Breast Prostate Pancreas
Africa Breast Cervix uteri Liver Prostate Lung

As shown here, CRC is one of the important types of cancer with a high incidence and mortality, but it has a good prognosis if it is detected early.4)

England data: CRC five-year age-standardized survival rate in %5)

Sex All stages Stage 1 Stage 2 Stage 3 Stage 4
Males 58.2 90.7 83.5 64.2 10.3
Females 58.6 93.1 84.9 65.9 10.3
Both sexes 58.4 91.7 84.1 64.9 10.3

Based on the above background, the purpose of cancer screening is to reduce cancer deaths by early detection and appropriate treatment. The fecal occult blood test such as fecal immunochemical test (FIT) has a scientific rationale to reduce cancer mortality,6-7) and enables rapid and non-invasive primary screening of CRC.
The incidence of early-stage CRC (diagnosed in patients <50 years) is increasing in many countries, including the United States, Canada, and Australia.8-10) To ensure more efficient screening for early-onset CRC, the American Cancer Society (ACS) has lowered the recommended age of target patients from 50 to 45 in 2018;11) in addition, the US Preventive Services Task Force (USPSTF) has updated its recommendations for CRC screening in October 2020 and has recommended to also screen individuals aged 45–49 years.12)

References

  • 1）Sung H, et al. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021;71:209-249.
  • 2）Center for Cancer Control and Information Services, National Cancer Center Japan: Projected Cancer Statistics, 2020. Available from: https://ganjoho.jp/en/public/statistics/short_pred.html
  • 3）International Agency for Research on Cancer, World Health Organization. Population fact sheets. Available from: https://gco.iarc.fr/today/fact-sheets-populations
  • 4）Colon Cancer. Am Fam Physician. 2018;97:Online. Available from: https://www.aafp.org/afp/2018/0515/p658-s1.html
  • 5）Office for National Statistics. Cancer survival in England - adults diagnosed. 2013 - 2017 edition of this dataset. Available from: https://www.ons.gov.uk/peoplepopulationandcommunity/healthandsocialcare/conditionsanddiseases/datasets/cancersurvivalratescancersurvivalinenglandadultsdiagnosed
  • 6）Guidelines for colorectal cancer screening based on efficacy evaluation (Ministry of Health, Labour and Welfare Cancer Research Grant 2004, “Research Group on Establishment of Appropriate Methods and Evaluation Methods for Cancer Screening,” March 24, 2005). Available from: http://canscreen.ncc.go.jp/guideline/daicyougan.html [Article in Japanese]
  • 7）Saito H, et al. A case-control study evaluating occult blood screening for colorectal cancer with hemoccult test and an immunochemical hemagglutination test. Oncol Rep. 2000; 7: 815-819.
  • 8）Siegel RL,et al. Global patterns and trends in colorectal cancer incidence in young adults. Gut. 2019; 68: 2179-2185.
  • 9）Araghi M, et al. Changes in colorectal cancer incidence in seven high-income countries: a population-based study. Lancet Gastroenterol Hepatol. 2019; 4: 511-518.
  • 10）Vuik FE, et al. Increasing incidence of colorectal cancer in young adults in Europe over the last 25 years. Gut. 2019; 68: 1820-1826.
  • 11）Wolf AMD, et al. Colorectal cancer screening for average-risk adults: 2018 guideline update from the American Cancer Society. CA Cancer J Clin. 2018; 68: 250-281.
  • 12）US Preventive Services Task Force, et al. Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2021 May 18;325(19):1965-1977.

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