Screening
Average-risk population
National Health Service (NHS)
The NHS recommends that bowel cancer screening is offered every 2 years to men and women from the age of 60 to 74 years using the home faecal immunochemical test kit.[172] People older than 74 years can request a screening test if they wish to continue to be screened. Anyone with an abnormal screening test result should be offered a colonoscopy.[172]
The NHS has begun reducing the age for bowel cancer screening to 50 years from April 2021, over 4 years.[172]
Some other initiatives by the NHS include:
National awareness campaigns to improve detection[173]
Providing home testing kits to those aged 54 years and over[174]
Providing routine preventative screening to thousands of people in England with a genetic condition[174]
Introduction of a specially designed tool to support FIT testing in people who are blind or partially sighted[175]
National Comprehensive Cancer Network (NCCN)[41]
The NCCN defines an average-risk individual as possessing the following characteristics:
Age 45-75 years
No personal history of adenoma or sessile serrated polyp (SSP) or colorectal cancer
No personal history of inflammatory bowel disease (IBD)
No personal history of high-risk colorectal cancer genetic syndromes
No personal history of cystic fibrosis
No personal history of childhood cancer
Negative family history for colorectal cancer
Negative family history for confirmed advanced adenoma (i.e., high-grade dysplasia, ≥1 cm, villous or tubulovillous histology) or an advanced SSP (≥1 cm, any dysplasia) in first-degree relatives.
Colorectal cancer screening is recommended in adults aged 45-75 years who might have a life expectancy of ≥10 years. The decision to screen between 76 and 85 years should be individualised and should include a discussion of the risks and benefits based on comorbidity status and estimated life expectancy.
A range of screening options are provided in the guidelines; screening should be individualised and include a discussion of the risks and benefits of each modality, as well as the preference and availability of the patient. Screening options are as follows:
Colonoscopy. If no polyps are found, rescreen with any modality in 10 years. If colonoscopy is incomplete or preparation is suboptimal, colonoscopy should be repeated as soon as possible and no later than 1 year after the index procedure. Capsule colonoscopy can be considered for patients who have had incomplete colonoscopy.
Stool-based tests: should be employed in individuals at average risk only when colonoscopy cannot be safely performed.
Guaiac-based testing. If negative, rescreen with any modality in 1 year
Faecal immunochemical test (FIT). If negative, rescreen with any modality in 1 year
Following a positive stool-based test, colonoscopy within 9 months is recommended for additional evaluation.
Multi-targeted stool DNA (mt-sDNA)-based testing. This is a combined multi-target stool DNA and occult blood test. It screens for the presence of known DNA alterations (KRAS mutations, aberrant NDRG4 and BMP3 methylation) during colorectal carcinogenesis in tumour cells shed into stool, as well as occult blood as measured by immunoassay.[145] If negative, rescreening is recommended with any modality in 3 years.
Flexible sigmoidoscopy. If no polyps are found, rescreen with any modality in 5-10 years. Colonoscopy is recommended in the event of biopsy-proven adenoma detection.
Computed tomographic (CT) colonography. If no polyps are found, rescreen with any modality in 5 years. Colonoscopy is recommended if abnormalities are found on CT colonography.
If colonoscopy is negative after a positive FIT or mt-sDNA-based testing and no additional symptoms are present, further tests are not required before the next recommended screening interval.
Colonoscopy is indicated as follow-up of abnormal findings from other screening modalities. During colonoscopy, any polyps should be removed if possible, and follow-up strategies should be based on the endoscopic and pathological findings. Polyps in the ascending colon are associated with greater cancer risk, warranting additional surveillance. Removed polyps should be examined for degree of dysplasia, as well as for histological features of SSPs. These are a type of polyp that can develop foci of dysplasia and have been associated with adenocarcinoma.
United States Preventive Services Task Force
The US Preventive Services Task Force recommends screening for colorectal cancer starting at age 45 years and continuing until age 75 years.[176]
The decision to screen for colorectal cancer in adults aged 76-85 years should be an individual one, taking into account the patient’s overall health and prior screening history.[176]
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 faecal occult blood test (FOBT), every year [
]
FIT, every year
FIT-DNA, every 1 or 3 years.
Direct visualisation 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 Gastroenterology (ACG)
The ACG colorectal cancer screening guidelines recommend:[86]
Screening average-risk individuals between the ages of 45 and 75 years to reduce the incidence of advanced adenoma, colorectal cancer, and mortality from colorectal cancer (while noting that evidence to support screening of individuals between 45 and 49 years is of very low quality)
That a decision to continue screening beyond age 75 years be individualised
Colonoscopy and FIT as the primary screening modalities for colorectal cancer screening
That the following intervals should be followed for screening modalities: FIT every 1 year; colonoscopy every 10 years.
American Gastroenterological Association (AGA)[60][177]
In the US, colorectal cancer screening prevalence is much lower among individuals who do not have access to health care due to lack of insurance or who do not have a primary care provider, and is likely to be lower in those who may struggle with transportation, child care, and time away from work. The AGA sets out a clear need for organised screening to reduce both colorectal cancer incidence and mortality.[177] They recommend that a screening programme should offer both colonoscopy and non-invasive screening options (as offering more than one screening test improves participation), patient education, outreach, and navigation support.[177]
Non-invasive tests include FIT, high-sensitivity faecal occult blood test, multi-target stool DNA-FIT test, and CT colonography. If these tests are positive, follow-up colonoscopy should be arranged.[177]
The AGA recommends the expansion of organised screening to include the follow-up of patients with high-risk adenomas (any adenoma ≥10 mm, or with villous histology, or high-grade dysplasia) or advanced sessile serrated lesions (defined as lesions ≥10 mm, or with cytological dysplasia, or a traditional serrated adenoma). There is evidence that colonoscopy surveillance can reduce colorectal cancer incidence and mortality for individuals with high-risk lesions.[177]
The AGA has issued following Best Practice Advice statements on risk stratification for colorectal cancer screening based on published literature and expert opinion:[60]
Individuals with a first-degree relative diagnosed with colorectal cancer, especially before the age of 50 years, should be considered at increased risk for colorectal cancer. Screening for these individuals should start 10 years before the age at which the youngest affected relative was diagnosed or at 40 years, whichever is earlier.
Individuals without a personal history of colorectal cancer, inflammatory bowel disease, hereditary colorectal cancer syndromes, other colorectal cancer predisposing conditions, or a family history of colorectal cancer should be considered at average risk for colorectal cancer. Screening for these individuals should start at 45 years.
Risk stratification for initiation of colorectal cancer screening should be based on an individual’s age, a known or suspected predisposing hereditary colorectal cancer syndrome, and/or a family history of colorectal cancer.
For individuals aged >75 years, screening decisions should be individualised, taking into account risks, benefits, screening history, and comorbidities.
Screening options for individuals at average risk should include: colonoscopy, faecal immunochemical test, flexible sigmoidoscopy plus faecal immunochemical test, multitarget stool DNA faecal immunochemical test, and computed tomography colonography, based on availability and individual preference.
For individuals at increased risk, colonoscopy should be used as the screening strategy.
All risk stratification tools for colorectal cancer screening derived from research should be examined for real-world effectiveness and cost-effectiveness in diverse populations before implementation.
US Multi-Society Task Force on Colorectal Cancer
The US Multi-Society Task Force on Colorectal Cancer recommends:[110][178]
Screening average-risk patients from 45 years
That the decision to start or continue screening in individuals aged 76-85 years should be personalised and based on prior screening history, life expectancy, risk of colorectal cancer, and personal preference
That screening is not recommended after age 85 years.
This guideline ranks the available screening tests into three tiers:
Colonoscopy every 10 years or FIT annually
Circulating tumour cells blood test every 5 years, FIT-fecal DNA every 3 years, and flexible sigmoidoscopy every 5-10 years
Capsule colonoscopy every 5 years.
American Cancer Society
The American Cancer Society recommends that adults aged 45 years and older, with an average risk of colorectal cancer, undergo regular screening with any of the following screening tests depending on patient preference and test availability:[179]
Colonoscopy every 10 years
CT colonography every 5 years
Flexible sigmoidoscopy every 5 years
Take-home high-sensitivity guaiac-based FOBT annually [
]
Take-home FIT annually
Multi-target stool-DNA test every 3 years.
All positive results on non-colonoscopy screening tests should be followed up with timely colonoscopy.
American College of Physicians (ACP)
The ACP recommends colorectal cancer screening in average-risk adults between the ages of 50 and 75 years.[180][181]
Suggested screening tests and intervals are:
FIT or high-sensitivity guaiac-based FOBT every 2 years
Colonoscopy every 10 years
Flexible sigmoidoscopy every 10 years plus FIT every 2 years.
Stool DNA testing is not recommended.
The ACP recommends that screening for colorectal cancer be discontinued in average-risk adults older than 75 years or in adults with a life expectancy of 10 years or less.[180][181]
Canadian Task Force on Preventive Health Care
The Canadian Task Force on Preventive Health Care recommends against using colonoscopy as a primary screening tool in asymptomatic adults aged 50 years and older who are not at high risk for colorectal cancer, citing inadequate evidence of colonoscopy's superiority to other screening tests, particularly FOBT.[182] However, these recommendations were classified as 'weak' based on a lack of evidence in randomised controlled trials.
Screening based on 15-year colorectal cancer risk
Screening with FIT every year, FIT every 2 years, sigmoidoscopy, or colonoscopy may be considered for adults aged 50-79 years whose 15-year risk of colorectal cancer is 3% or higher. Each strategy reduces colorectal cancer mortality by a similar amount (5 or 6 deaths prevented per 1000 people screened).[183] BMJ: colorectal cancer screening with faecal immunochemical testing, sigmoidoscopy or colonoscopy: a clinical practice guideline. Opens in new window
Familial or inherited risk
UK guidelines[184]
UK guidelines recommend that screening starts at age 50 years (55 years for lower-risk individuals) in patients with a family history of colorectal cancer in a first-degree relative.
National Comprehensive Cancer Network (NCCN)[41]
The NCCN recommends screening colonoscopy for patients with any of the following:
≥1 first-degree relative with colorectal cancer at any age. Colonoscopy should begin at age 40 years or 10 years before the earliest diagnosis of colorectal cancer. It should be repeated every 5 years or if positive, as per colonoscopy findings.
Second- and third-degree relatives with colorectal cancer at any age. Colonoscopy should begin at age 45 years. Repeat every 10 years or if positive, repeat as per colonoscopy findings.
First-degree relative with confirmed advanced adenoma(s) (i.e., high-grade dysplasia, ≥1 cm, villous or tubulovillous histology, traditional serrated adenomas), or advanced SSPs (≥1 cm, any dysplasia) at any age. Colonoscopy should begin at age 40 years or at the age of onset of adenoma in the relative, whichever is first. It should be repeated every 5-10 years or if positive, as per colonoscopy findings.
US Multi-Society Task Force on Colorectal Cancer[110]
The US Multi-Society Task Force on Colorectal Cancer recommends screening colonoscopy for patients with:
Two or more first-degree relatives with colorectal cancer diagnosed at any age, or
A single first-degree relative with colon cancer or adenomatous polyps diagnosed when the patient was younger than 60 years.
Colonoscopy should begin at 40 years, or 10 years younger than the earliest diagnosis in the family, whichever comes first, and should be repeated every 5 years. People with a single first-degree relative diagnosed at or over ages 60 years should be offered average-risk screening options, beginning at the age of 40 years.
American College of Gastroenterology (ACG)[86]
The ACG recommends:
Initiating colorectal cancer screening with a colonoscopy at age 40 years, or 10 years before the youngest affected relative received diagnosis, whichever is earlier, for individuals with colorectal cancer or advanced polyp in one first-degree relative at age <60 years or colorectal cancer or advanced polyp in two or more first degree relatives at any age. Interval colonoscopy every 5 years.
Consideration of genetic evaluation with higher familial colorectal cancer burden.
Initiating colorectal cancer screening at age 40 years, or 10 years before the youngest affected relative received diagnosis, and then resuming average-risk screening recommendations for individuals with colorectal cancer or advanced polyp in one first-degree relative at age 60 years or more.
Average-risk colorectal cancer screening recommendations for individuals with one second-degree relative with colorectal cancer or advanced polyp.
High-risk syndromes
Familial adenomatous polyposis (FAP):
ACG guidelines recommend that screening for colorectal cancer in patients at risk for, or affected by, FAP should begin at puberty (aged 10-12 years); surveillance should be by annual colonoscopy or flexible sigmoidoscopy.[185]
NCCN guidelines specify follow-up intervals for colorectal cancer screening following surgery for FAP:[93]
Patients with a retained rectum following total abdominal colectomy with ileorectal anastomosis should undergo endoscopic rectal examination every 6-12 months.
After proctocolectomy with ileal pouch-anal anastomosis, the ileal pouch and rectal cuff should be evaluated endoscopically annually.
If the patient had a proctocolectomy with end-ileostomy, consider careful visualisation and stoma inspection by ileoscopy annually to evaluate for polyps or malignancy.
Chemoprevention should only be considered in select patients as an adjunct to standard endoscopic or surgical treatment with a full discussion of the risks, benefits, and alternatives.
Lynch syndrome (hereditary non-polyposis colorectal cancer):
The ACG and US Multi-Society Task Force on Colorectal Cancer recommend that screening for colorectal cancer in patients at risk for, or affected by, Lynch syndrome should begin between ages 20 and 25 years; surveillance should be by colonoscopy every 1-2 years.[185][186] Annual colonoscopy should be considered in confirmed mutation carriers.[185][186]
The American College of Obstetricians and Gynecologists (ACOG) recommends that all women with Lynch syndrome should undergo colonoscopy every 1-2 years, starting at ages 20-25 years, or 2 to 5 years before the earliest colon cancer diagnosis in the family, whichever comes first.[61] Further, the ACOG recommends considering genetic risk assessment for unaffected women having a first-degree relative affected with colorectal cancer who was either diagnosed before the age of 60 years or was identified to be at risk of Lynch syndrome by systematic clinical screens.[61]
The NCCN has different colorectal cancer surveillance guidelines depending on the pathogenic variant of Lynch syndrome identified on genetic testing. For MLH1 and MSH2/EPCAM variant carriers, colonoscopy should start between the ages of 20-25 years, or 2-5 years younger than the youngest diagnosis age in the family, whichever comes first, and should be repeated every 1-2 years. For MSH6 and PMS2 pathogenic/likely pathogenic (P/LP) variant carriers, consider a later age of onset for colonoscopy initiation, such as at aged 30-35 years, or 2-5 years younger than the age of any relative with colorectal cancer if diagnosed before age 30 years, repeating every 1-3 years.[93]
MUTYH/MYH-associated polyposis (MAP):
ACG guidelines recommend that screening for colorectal cancer in patients at risk for, or affected by, MAP should begin at puberty (aged 10-12 years); surveillance should be by annual colonoscopy.[185]
NCCN guidelines differ. They recommend that patients should undergo surveillance colonoscopy and complete polypectomy every 1-2 years, beginning no later than age 25-30 years; earlier colonoscopy may be indicated based on family history.[93]
Surgery in the form of colectomy with ileorectal anastomosis is recommended in most cases of significant polyposis not manageable by polypectomy. After this operation, endoscopic evaluation of the rectum every 6-12 months is recommended, depending on polyp burden.[93]
Peutz-Jeghers syndrome (PJS)
Patients with PJS should undergo a multidisciplinary approach to cancer screening because of very high cumulative lifetime risk of cancers in multiple organs. Baseline colonoscopy, upper gastrointestinal (GI) endoscopy, and video capsule endoscopy or magnetic resonance enterography (for small bowel lesions) should all be carried out between ages 8 and 10 years. Where characteristic polyps are detected in the stomach, duodenum, or colon, both upper and lower GI endoscopy should be repeated every 2-3 years. Where no Peutz-Jeghers polyps are detected at baseline endoscopy, surveillance should be repeated at 18 years of age, or earlier if symptoms occur, and then 3-yearly. Colorectal polyps ≥0.5 cm should be removed, and an attempt should be made to remove all polyps if endoscopically possible.[187]
Juvenile polyposis syndrome (JPS)
Paediatric patients with JPS should undergo colonoscopy and upper GI endoscopy between ages 12 and 15 years, or earlier if symptomatic, with surveillance repeated every 1-3 years depending on the polyp burden. Colorectal polyps ≥0.5 cm should be removed, and an attempt should be made to remove all polyps if endoscopically possible.[187] If no polyps are found, screening can resume at age 18 years and should be repeated every 1-3 years.[93]
PTEN-hamartoma tumour syndrome (PHTS)
Colonoscopic surveillance should start at age 35 years, and be repeated every 5 years, or more frequently if the patient is symptomatic or polyps are found. Initial colonoscopy should be carried out sooner if any relative was diagnosed with colorectal cancer below the age of 40 years; the starting age should be 10 years before the age at which the relative was diagnosed.[187]
Personal history of polyps found at colonoscopy
NCCN guidelines recommend a surveillance programme for patients aged 45-75 years with adenomas, provided that life expectancy is 10 or more years. Surveillance of patients between 76 and 85 years should be individualised. Surveillance guidelines are as follows:[41]
After removal of low-risk adenomas (≤2 tubular adenomas that are <1 cm), colonoscopy should be repeated between 7 and 10 years, then in a further 10 years if this is normal.
After removal of low-risk SSPs, defined as ≤2 SSPs that are <1 cm without dysplasia, colonoscopy should be repeated in 5 years, then in a further 10 years if this is normal.
Individuals with high-risk polyps (advanced or multiple polyps) should have a repeat colonoscopy in 3 years. If the examination is normal, subsequent surveillance colonoscopy is recommended in 5 years. Advanced polyps include the following: traditional serrated adenomas (TSA); adenomas with high-grade dysplasia or SSPs with dysplasia; adenomas/SSPs ≥1 cm; hyperplastic polyps (≥1 cm); polyps with villous or tubulovillous histology. Polyps are considered multiple when there are between 3 and 9 present.
In individuals with ≥10 cumulative adenomatous polyps and/or SSPs or those with ≥20 polyps, a polyposis syndrome should be considered and genetic testing may be appropriate. Colonoscopy should be repeated in 1 year or individual management should be considered.
Large polyps:
Patients who have undergone complete resection of large polyps (≥1 cm) with no high-risk endoscopic features for invasive cancer should have follow-up colonoscopy in 1-3 years, then again in a further 3 years if no recurrence is found.
In the case of patients who have had excision of large polyps with high-risk features (lateral spreading lesions ≥40 mm, intraprocedural bleeding requiring endoscopic control, high-risk dysplasia, or macroscopic tissue ablation performed), follow-up colonoscopy is recommended within 6 months. If there is no disease recurrence, colonoscopy should be repeated within 1 year, and subsequently in 3 years.
Patients with large pedunculated polyps should have follow-up colonoscopy in 3 years.
Patients with a personal history of colorectal cancer should undergo routine tumour testing with immunohistochemistry and/or microsatellite instability for Lynch syndrome or mismatch repair deficiency (MMR). Germline multigene testing should be considered for all individuals aged <50 years with a diagnosis of colorectal cancer for evaluating Lynch syndrome and other hereditary cancer syndromes.[41]
Inflammatory bowel disease (IBD)
Risk factors for dysplasia in patients with IBD include: ulcerative colitis; extensive colitis; colonic stricture; primary sclerosing cholangitis (PSC); family history of colorectal cancer (especially with diagnosis <50 years of age); personal history of dysplasia; and severe longstanding inflammation. Patients with proctitis and proctosigmoiditis are likely at little or no increased risk of colorectal cancer compared with the general population and should be managed as average risk.[41]
Patients with colon involvement should undergo colonoscopic screening (with systematic biopsies) for colorectal cancer 8 years after symptom onset.[188][189]
Surveillance should be every 1-3 years; higher-risk patients (e.g., those with active extensive disease or concomitant PSC) should undergo annual surveillance.[171][188] NCCN and AGA guidelines recommend that if PSC is present, annual surveillance colonoscopies should start at the time of PSC diagnosis.[41][189] Family history of colorectal cancer is another important risk factor for developing colorectal cancer in patients with IBD, and such individuals may benefit from earlier initiation of colonoscopic surveillance.[41]
Surveillance is ideally performed when colonic disease is in remission.[171]
UK guidelines recommend that all patients with ulcerative colitis or Crohn's disease should have a screening colonoscopy approximately 10 years after the onset of colitic symptoms to assess disease extent and other endoscopic risk factors.[184]
Subsequent surveillance is influenced by risk:[184]
Lower risk - every 5 years: extensive colitis with no active endoscopic/histological inflammation, or left-sided colitis, or Crohn's disease of <50% of the colon
Intermediate risk - every 3 years: extensive colitis with mild active endoscopic/histological inflammation, or post-inflammatory polyps, or family history of colorectal cancer
Higher risk - every year: extensive colitis with moderate to severe active endoscopic/histological inflammation, or strictures in the past 5 years, or dysplasia in the past 5 years declining surgery, or primary sclerosing cholangitis, or family history of colorectal cancer in a first-degree relative aged under 50 years.
Surveillance colonoscopies should be performed when the disease is in remission.[184]
Acromegaly
Guidelines published by the British Society of Gastroenterology recommend colonoscopic screening beginning at the age of 40 years, repeated every 5-10 years if the initial colonoscopy is negative.[184]
If adenomas are found at first screening, or serum IGF-1 levels are above the maximum of the age-corrected normal range, patients should be offered 3-yearly screening.[184]
Subsequent surveillance is influenced by risk:[184]
Lower risk - every 5 years: extensive colitis with no active endoscopic/histological inflammation, or left sided colitis, or Crohn's disease of <50% of the colon
Intermediate risk - every 3 years: extensive colitis with mild active endoscopic/histological inflammation, or post-inflammatory polyps, or family history of colorectal cancer
Higher risk - every year: extensive colitis with moderate to severe active endoscopic/histological inflammation, or strictures in the past 5 years, or dysplasia in the past 5 years declining surgery, or primary sclerosing cholangitis, or family history of colorectal cancer in a first-degree relative aged under 50 years.
Surveillance colonoscopies should be performed when the disease is in remission.[184]
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