Colorectal Cancer Screening
Guidelines on colorectal screening have been issued by the following organizations:
American Cancer Society (ACS), US Multi-Society Task Force on Colorectal Cancer, and American College of Radiology
U.S. Preventive Services Task Force (USPSTF)
American College of Physicians (ACP)
American College of Gastroenterology (ACG)
National Comprehensive Cancer Network (NCCN)
While all the guidelines recommend routine screening for colorectal cancer and adenomatous polyps in asymptomatic adults, they differ with regard to frequency of screening and age at which to discontinue screening, as well as the preferred screening method. Although the customary age for starting screening in persons at average risk has been 50 years, the increasing incidence of colorectal cancer in younger people has prompted several organizations to lower the recommended starting age to 45 years. For high-risk patients, the recommendations differ regarding the age at which to begin screening, as well as the frequency and method of screening.
In contrast, a 2019 guideline on colorectal cancer screening from an international panel of experts recommends using risk calculations to guide screening, with screening limited to patients with an elevated level of risk.
American Cancer Society (ACS), US Multi-Society Task Force on Colorectal Cancer, and American College of Radiology
A joint guideline developed by the American Cancer Society, US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology recommends that screening for colorectal cancer and adenomatous polyps start at age 50 years in asymptomatic men and women.
In addition, individuals with any of the following colorectal cancer risk factors should undergo colonoscopy at an earlier age and more frequently than average risk individuals:
Family history of colorectal cancer or polyps
Family history of a hereditary colorectal cancer syndrome such as familial adenomatous polyposis (FAP) or hereditary non-polyposis colon cancer (HNPCC)
Personal history of colorectal cancer
Personal history of chronic inflammatory bowel disease (ulcerative colitis or Crohn disease)
Screening options for average-risk adults consist of tests that detect adenomatous polyps and cancer, and tests that primarily detect cancer. Any one of these tests can be used for screening.
Tests that detect adenomatous polyps and cancer, and their recommended frequency, include the following:
Flexible sigmoidoscopy every 5 years
Colonoscopy every 10 years
Double-contrast barium enema every 5 years
Computed tomographic (CT) colonography every 5 years
Tests that primarily detect cancer, and their recommended frequency, include the following:
Annual guaiac-based fecal occult blood test (FOBT) with high test sensitivity for cancer
Annual fecal immunochemical test (FIT) with high test sensitivity for cancer
Stool DNA test with high sensitivity for cancer, interval uncertain
In June 2017 the US Multi-Society Task Force on Colorectal Cancer issued updated screening recommendations that divide screening tests into three tiers, based upon their effectiveness.
Tier 1 tests consist of the following:
Colonoscopy every 10 years
Annual FIT
Tier 2 tests consist of the following:
CT colonography every 5 years
FIT–fecal DNA every 3 years
Flexible sigmoidoscopy every 5–10 years
Tier 3 testing is capsule colonoscopy every 5 years. Septin 9 testing is not recommended.
Suggested timing of initial screening and intervals for subsequent testing for different risk populations are as follows:
For patients at average risk, testing with a tier 1 test should begin at age 45 years for African Americans and at age 50 for patients of all other races.
For patients with a family history of colorectal cancer or advanced adenoma that was diagnosed before age 60 years in one first-degree relative or at any age in two first-degree relatives, testing should begain with colonoscopy at an age10 years younger than the youngest age at diagnosis of a first-degree relative, or age 40, to be repeated every 5 years.
In patients with one first-degree relative with colorectal cancer, advanced adenoma, or an advanced serrated lesion diagnosed at age 60 or older, screening should begin with a tier 1 test at age 40 and continue at the same intervals as inaverage-risk patients.
Colonoscopy screening should be discontinued in patients aged 75 or older with prior negative screening tests or whose life expectancy is less than 10 years, or in those 85 years or older without prior screening.
American Cancer Society update
In May 2018 the ACS revised its colorectal screening guidelines, advising that regular screening for people at average risk start at age 45 years.
Additional ACS recommendations include the following:
For people in good health and with a life expectancy of more than 10 years, regular colorectal cancer screening should continue through the age of 75.
People ages 76 through 85 should make a decision with their medical provider about whether to continue screening, based on their own personal preferences, life expectancy, overall health, and prior screening history.
People over 85 should discontinue colorectal cancer screening.
U.S. Preventive Services Task Force (USPSTF)
In May 2021 the USPSTF revised its colorectal screening guidelines. While maintaining its grade A recommendation of screening for colorectal cancer in all adults aged 50 to 75 years, the USPSTF added a grade B recommendation for screening in adults age 45 to 49 years. For adults aged 76 to 85 years, the decision to screen should be individualized, taking into account the patient’s overall health and prior screening history (C recommendation).
The USPSTF advises that screening is more likely to benefit older patients who have never been screened than those who have undergone screening, and is more likely to benefit patients who are healthy enough to undergo treatment for colorectal cancer treatment and who do not have other medical conditions limiting their life expectancy.
The USPSTF does not recommend colorectal cancer screening for adults older than 85 years.
The USPSTF notes that colorectal screening is substantially underused. As part of a strategy to increase screening rates, the guidelines provide a range of screening options rather than a ranking of tests.
Stool-based screening tests and intervals are as follows:
Guaiac-based fecal occult blood test (FOBT), every year
Fecal immunochemical test (FIT), every year
FIT-DNA, every 1 or 3 years
Direct visualization screening tests and intervals are as follows:
Colonoscopy, every 10 years
Computed tomographic (CT) colonography, every 5 years
Flexible sigmoidoscopy, every 5 years
Flexible sigmoidoscopy with FIT; sigmoidoscopy every 10 years, with FIT every year
American College of Physicians (ACP)
In 2015, the American College of Physicians recommended that average-risk adults aged 50 to 75 years should be screened for colorectal cancer by one of the following strategies
:
Annual high-sensitivity FOBT or FIT
Flexible sigmoidoscopy every 5 years
High-sensitivity FOBT or FIT every 3 years plus flexible sigmoidoscopy every 5 years
Colonoscopy every 10 years
Interval screening with fecal testing or flexible sigmoidoscopy in adults having 10-year screening colonoscopy is not recommended. Average-risk adults younger than 50 years, older than 75 years, or with an estimated life expectancy of less than 10 years should not be screened.
American College of Gastroenterology
American College of Gastroenterology (ACG) 2021 guidelines recommend colorectal cancer screening in average-risk individuals of age 50 to 75 years, and suggest screening in average-risk individuals of age 45 to 49 years. The ACG recommends colonoscopy and FIT as the primary modalities for colorectal cancer screening.
Further ACG suggestions regarding colorectal cancer screening include the following:
Initiate colorectal cancer screening with a colonoscopy at age 40 or 10 years before the youngest affected relative, whichever is earlier, in individuals in whom a first-degree relative has had colorectal cancer or an advanced polyp before age 60 years or in whom two or more first-degree relatives have had colorectal cancer or an advanced polyp at any age; perform interval colonoscopy every 5 years.
Consider genetic evaluation in individuals with a higher familial colorectal cancer burden (higher number and/or younger age of affected relatives).
In individuals in whom a first-degree relative has had colorectal cancer or an advanced polyp at age 60 years or older, initiate colorectal cancer screening at age 40 or 10 years before the youngest affected relative, then resume screening according to average-risk screening recommendations.
In individuals with a second-degree relative with colorectal cancer or an advanced polyp, follow average-risk colorectal cancer screening recommendations.
Decide whether to continue screening beyond age 75 years on an individualized basis.
In individuals unable or unwilling to undergo colonoscopy or FIT, consider screening with flexible sigmoidoscopy, multitarget stool DNA test, CT colonography, or colon capsule.
Do not use the Septin 9 methylated DNA test Septin 9 for screening.
National Comprehensive Cancer Network (NCCN)
The National Comprehensive Cancer Network (NCCN) has released separate guidelines for average-risk and high-risk individuals.
For average individuals, the recommendations are nearly identical to those of the joint American Cancer Society (ACS), US Multi-Society Task Force on Colorectal Cancer, and American College of Radiology. However, in 2021 the NCCN lowered the age for starting screening in average-risk individuals from 50 years to 45 years.
The NCCN criteria for average risk are as follows
Age ≥50 y
No history of adenoma, sessile serrated polyp, or colorectal cancer
No history of inflammatory bowel disease
Negative family history for colorectal cancer or confirmed advanced adenoma (ie, high-grade dysplasia, ≥1 cm, villous or tubulovillous histology) or an advanced sessile serrated polyp (≥1 cm, any dysplasia)
The NCCN guidelines provide screening recommendations for patients at increased risk due to any of the following
:
Personal history of adenoma or sessile serrated polyp
Personal history of colorectal cancer
Inflammatory bowel disease (ulcerative colitis, Crohn’s disease)
Positive family history
The guidelines also specify recommendations for patients with the following high-risk syndromes
:
Lynch syndrome (hereditary nonpolyposis colorectal cancer)
Classic familial adenomatous polyposis (FAP)
Attenuated familial adenomatous polyposis (AFAP)
MUTHYH-associated polyposis (MAP)
Peutz-Jeghers syndrome (PJS)
Juvenile polyposis syndrome (JPS)
Serrated polyposis syndrome (SPS)
Colonic adenomatous polyposis of unknown etiology
Cowden syndrome/PTEN hamartoma tumor syndrome
Li-Fraumeni syndrome
Individuals meeting one or more of the following criteria should receive further evaluation for polyposis syndromes
:
Individuals with more than 10 adenomas detected (FAP, AFAP, MAP, and other rare genetic causes of multiple adenomatous polyps)
Individuals with more than 2 hamartomatous polyps (PJS, JPS and Cowden/PTEN hamartoma tumor syndrome)
Individuals with 5 or more serrated polyps proximal to the rectum
Family members with a known high-risk syndrome associated with colorectal cancer, with or without a known mutation
Individuals with a desmoid tumor, hepatoblastoma, cribriformmorular variant of papillary thyroid tumor (FAP, AFAP, MAP)
Risk-based screening
An international panel of experts has published colorectal cancer screening guidelines that recommend risk-based screening for adults aged 50-79 years with no prior screening, no symptoms of colorectal cancer, and a life expectancy of at least 15 years.
For individuals with an estimated 15-year colorectal cancer risk below 3%, the panel suggests no screening (weak recommendation). For individuals with an estimated 15-year risk above 3%, the panel suggests screening with one of the following options:
FIT every year
FIT every 2 years
A single sigmoidoscopy
A single colonoscopy
Calculation of 15-risk for colorectal cancer can be made using the online QCancer calculator. (Note that this calculator was developed for the United Kingdom population.)
Lynch Syndrome
Hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome, is a common autosomal dominant syndrome characterized by early age at onset, neoplastic lesions, and microsatellite instability (MSI). Guidelines for Lynch syndrome screening have been developed by the National Cancer Institute (Bethesda guidelines) and the NCCN.
Because cancers with MSI account for approximately 15% of all colorectal cancers, in 1996 the National Cancer Institute developed the Bethesda guidelines for the identification of individuals with HNPCC who should be tested for MSI. These guidelines were most recently revised in 2002.
Th NCCN criteria for the evaluation of Lynch syndrome (LS) include the following
:
Known LS pathogenic variant in family
Personal history of colorectal, endometrial, or other LS-associated cancer
Family history of a first-degree relative with colorectal or endometrial cancer diagnosed before age 50
Family history of a first-degree relative with colorectal or endometrial cancer and another synchronous or metachronous LS-related cancer
Family history of 2 or more first-degree or second-degree relatives with LS-related cancer, including 1 or more diagnosed before age 50
Family history of 3 or more first-degree or second-degree relatives with LS-related cancers
The American Gastroenterological Association recommends testing all patients with colorectal cancer for Lynch syndrome. The tumor should be tested for MSI or with immunohistochemistry for MLH1, MSH2, MSH6, and PMS2 proteins.
The European Society for Medical Oncology (ESMO) guidelines for familial risk-colorectal cancer
, which have been endorsed by the American Society of Clinical Oncology (ASCO)
includes the following recommendations:
Tumor testing for DNA mismatch repair (MMR) deficiency with immunohistochemistry for MMR proteins and/or MSI should be assessed in all patients with colorectal cancer. As an alternate strategy, tumor testing should be carried out in individuals with colorectal cancer younger than 70 years, or those older than 70 years who fulfill any of the revised Bethesda guidelines
If loss of MLH1/PMS2 protein expression is observed, analysis of BRAF V600E mutation or analysis of methylation of the MLH1 promoter should be conducted to rule out a sporadic case. If tumor is MMR deficient and somatic BRAF mutation is not detected or MLH1 promoter methylation is not identified, testing for germline mutations is indicated.
If loss of any of the other proteins (MSH2, MSH6, PMS2) is observed, germline genetic testing should be carried out for the genes corresponding to the absent proteins (eg, MSH2, MSH6, EPCAM, PMS2, or MLH1).
Full germline genetic testing for Lynch syndrome should include DNA sequencing and large rearrangement analysis.
The American College of Gastroenterology recommendations are in general agreement with ESMO.