Colorectal Cancer Screening

How to Cite This Chapter: Armstrong D. Colorectal Cancer Screening. McMaster Textbook of Internal Medicine. Kraków: Medycyna Praktyczna. https://empendium.com/mcmtextbook/chapter/B31.II.4.72.4 Accessed June 02, 2020.
Last Updated: January 31, 2020
Last Reviewed: January 31, 2020
Chapter Information

IntroductionTop

Colorectal cancer (CRC) is the third most common malignancy and the fourth most common cause of cancer-related death worldwide. It is predicted that there will be 2.2 million new CRC cases and 1.1 million CRC-related deaths by 2030. More than 90% of CRC cases are thought to arise, over periods ≥10 years, from preexisting adenomas, as part of an adenoma-carcinoma development sequence; however, the prevalence of adenomas in individuals aged 50 to 75 years ranges from 22% to 58% and most adenomas do not progress to CRC. CRC survival rates at 5 years fall from 90% in those with localized disease to 70% in those who have local lymph node involvement and 12% in those who have distant metastases.

Risk factors for CRC include a family history of CRC, advanced colon polyps, a genetic syndrome, a personal history of inflammatory bowel disease, or abdominal radiation for childhood malignancy. About 3% to 10% of adults report having ≥1 first-degree relative (FDR) with colon cancer and ~0.3% report having ≥2 FDRs with CRC. However, at least three-quarters of CRC cases are sporadic, occurring in individuals who have no family history and are considered to be at average risk of developing CRC. The incidence of CRC in average-risk individuals aged <50 years is low but rises >10-fold over the next 4 decades of life.

The high prevalence and natural history of CRC have led to recommendations for screening strategies appropriate for individuals at average risk and for those at high risk. In many countries, including the United States, CRC screening is “opportunistic,” arising directly from an interaction between the patient and the health-care provider. Conversely, in several European countries, Australia, and Canada, CRC screening is “programmatic” or “organized,” such that it is offered to all eligible patients in a population or health-care system. In general, programmatic screening is offered to average-risk individuals, while for high-risk individuals the screening recommendations are to some extent modified. The advantages of programmatic screening include facilitated access for all eligible individuals, quality assurance, follow-up of abnormal screening tests, and minimization of overscreening.

Most guidelines recommend that CRC screening be started at the age of 50 years for average-risk individuals; to date, there is no widespread support for proposals that screening be started at the age of 45 years, either for African Americans or for all average-risk individuals. Most programmatic screening is discontinued for average-risk individuals once they reach the age of 75 years, in recognition of the fact that the risks of screening and treatment increase in older populations and may outweigh the potential benefits.

GoalsTop

To diminish the incidence and mortality of CRC, screening should detect early-stage, potentially curable CRCs as well as high-risk premalignant adenomatous polyps and other conditions, such as inflammatory bowel disease (IBD), which may predispose to CRC.

The specific management strategies adopted in an individual who has a positive CRC screening test depend on the individual’s history and risk factors as well as on the employed screening test.

TestsTop

1. Fecal occult blood test (FOBT) screening was initially based on fecal guaiac testing (gFOBT) but it is being increasingly supplanted by fecal immunochemical testing (FIT), especially for programmatic screening. Using gFOBT, it is possible to detect the heme component of hemoglobin in stool when heme catalyzes the oxidization of alpha-guaiaconic acid to generate a blue color on the guaiac test paper after the addition of hydrogen peroxide. FIT detects the globin component of hemoglobin in stool using specific antibodies; it has greater sensitivity for the detection of CRC and specificity comparable with gFOBT. FIT does not involve any dietary or medication restrictions and generally requires only 1 stool sample rather than 3, as is the case for gFOBT. Fecal DNA screening testing (FIT-DNA) detects biomarkers associated with CRC and advanced adenomas but has more false-positive results than FIT.

A positive stool test result should be followed by full colonoscopy to determine whether the patient has CRC, which should be localized and confirmed histologically if present; an adenoma or adenomas, which should be removed, if possible, during the colonoscopy; or other lesions (eg, IBD, vascular lesions) that require treatment or further investigation.

gFOBT has been shown to reduce CRC-related mortality and the incidence of late-stage CRC (Table 11.1-1). FIT likely offers greater sensitivity and higher detection rates than gFOBT for both CRC and advanced adenomas; a systematic review showed FIT was associated with higher participation rates (ie, higher proportions of patients who were invited proceeded to participation) related to the ease of completing the test. To date, there are no randomized controlled trials to show that FIT-DNA reduces the mortality of CRC or the incidence of late-stage CRC.

2. Flexible sigmoidoscopy (FS) allows inspection and biopsy of the rectum and left colon. It can generally be performed with limited patient preparation and no sedation and is associated with lower complication rates than colonoscopy. FS permits direct diagnosis of CRC, polyps, or other mucosal lesions in the left colon, but full colonoscopy is recommended if CRC or polyps are found, as FS cannot generally visualize more than the most distal 60 cm of the colon.

Similarly to gFOBT, FS has been shown to reduce CRC-related mortality and the incidence of late-stage CRC (Table 11.1-1).

3. Colonoscopy allows inspection of the entire colon, as far as the cecum, provided that the procedure is completed satisfactorily. It permits direct diagnosis of CRC, polyps, or other lesions and, in most cases, removal of significant polyps and biopsy of any areas of abnormal mucosa. Colonoscopy has the highest sensitivity and specificity for the diagnosis of CRC, adenomas, and other lesions. However, it is also associated with a higher adverse event rate than FS and requires more extensive and less well-tolerated bowel preparation, conscious sedation and, often, greater loss of time from work.

To date, there is no high quality evidence to show that screening colonoscopy reduces mortality for CRC or the incidence of late-stage CRC, although observational studies and data modelling suggest that overall outcomes for colonoscopy are similar to those for gFOBT, FIT, and FS.Evidence 1Moderate Quality of Evidence (moderate confidence that we know true effects of the intervention). Quality of Evidence lowered due to the risk of bias. Lin JS, Piper MA, Perdue LA, et al. Screening for Colorectal Cancer: A Systematic Review for the U.S. Preventive Services Task Force [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2016 Jun. Available from http://www.ncbi.nlm.nih.gov/books/NBK373584/ PubMed PMID: 27441328. US Preventive Services Task Force, Bibbins-Domingo K, Grossman DC, Curry SJ, et al. Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2016 Jun 21;315(23):2564-2575. doi: 10.1001/jama.2016.5989. Erratum in: JAMA. 2016 Aug 2;316(5):545. Erratum in: JAMA. 2017 Jun 6;317(21):2239. PMID: 27304597.

4. Other screening tests, including computed tomography (CT) colonography, colon capsule endoscopy, barium enema, blood-based markers, and digital rectal examination have been evaluated for CRC screening, but there is no high quality evidence to show that any of these reduces CRC incidence or mortality. Other than CT colonography, none of these is recommended for screening by any of the major guidelines.

Risk AssessmenTTop

Risk factors for CRC include a family history of CRC (eg, recognized familial genetic syndromes and nonsyndromic familial CRC), family history of documented advanced adenomas, and personal history of IBD, adenomas, or CRC. A family history is associated with a 2- to 6-fold increase in the risk of CRC.

Risk assessment for CRC requires information on the individual’s family history of CRC and adenomas, including the number of affected family members, their degree of relatedness, and the age of diagnosis in addition to information regarding familial genetic syndromes and personal medical history of CRC, adenomas, and IBD (duration, extent, and location). An initial risk assessment in individuals aged <40 years will identify those who require screening before the age of 50 years and those who may require genetic testing.

ApproachTop

Average-Risk Individuals (General Population)

The major guidelines are broadly in agreement that CRC screening should be offered to all individuals aged 50 to 74 or 75 years, although there are some differences between guidelines with respect to the recommended first-line test.

For average-risk individuals aged 50 to 74 years, the Canadian Task Force on Preventive Health Care (CTFPHC) recommends:

1) FOBT (gFOBT or FIT) every 2 years; or

2) FS every 10 years.

This is supported by moderate-quality evidence, the recommendation being strong for individuals aged 60 to 74 years and weak for individuals aged 50 to 59 years. The weak recommendation for younger individuals is based on the lower incidence of CRC and, hence, a lower expected absolute benefit in those aged 50 to 59 years.

The CTFPHC suggests against CRC screening for individuals aged >75 years and against the use of colonoscopy for CRC screening (both weak recommendations with low-quality evidence). However, current US recommendations for average-risk individuals endorse the use of stool-based tests and structural examinations without prioritizing either class of tests. For stool-based tests, the American Cancer Society endorses FIT or high-sensitivity gFOBT every year or a multitarget stool DNA test every 3 years, while for structural examinations, they endorse colonoscopy every 10 years, CT colonography every 5 years, or FS every 5 years as acceptable options, depending on patient preference and test availability.

Full colonoscopy should be performed in all individuals who have a positive FOBT or ≥1 adenoma at FS. Upper endoscopy is not recommended routinely in otherwise asymptomatic individuals who have had a positive screening FOBT and no explanatory findings at colonoscopy.

The main adverse outcomes of CRC screening are attributable to colonoscopy, whether performed as the initial screening test or as a follow-up to a positive FOBT or FS. A systematic review and meta-analysis of studies up to December 2015 reported overall colonoscopy-related adverse event rates of 1/2000 procedures for perforation, 1/400 procedures for bleeding, and estimated 1/35,000 procedures for death.Evidence 2Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to indirectness. Reumkens A, Rondagh EJ, Bakker CM, Winkens B, Masclee AA, Sanduleanu S. Post-Colonoscopy Complications: A Systematic Review, Time Trends, and Meta-Analysis of Population-Based Studies. Am J Gastroenterol. 2016 Aug;111(8):1092-101. doi: 10.1038/ajg.2016.234. Epub 2016 Jun 14. PMID: 27296945.

High-Risk Individuals

1. Family history: For individuals who have 1 FDR with CRC, the Canadian Association of Gastroenterology (CAG) guideline on screening in individuals with a family history recommends screening colonoscopy with FIT as a second-line option, starting at the age of 40 to 50 years or 10 years younger than the age of CRC diagnosis for the FDR, whichever is earlier. Recommended screening intervals after a negative test are 5 to 10 years for colonoscopy and 1 to 2 years for FIT. For those who have ≥2 FDRs with CRC, the CAG family history guideline recommends screening colonoscopy starting at the age of 40 years or 10 years younger than the age of the earliest FDR’s diagnosis and a subsequent screening interval of 5 years. Individuals who have second-degree relatives with CRC should follow average-risk screening guidelines.

For those who have ≥1 FDR with a documented advanced adenoma, the family history guideline recommends colonoscopy or FIT, starting at the age of 40 to 50 years or 10 years younger than the age of the earliest FDR’s diagnosis, whichever is earlier. Recommended screening intervals after a negative test are 5 to 10 years for colonoscopy and 1 to 2 years for FIT.

Screening and genetic testing strategies for individuals who have a personal or family history of high-risk genetic syndromes, such as familial adenomatous polyposis (FAP), attenuated FAP (AFAP), Lynch syndrome (hereditary nonpolyposis colon cancer [HNPCC]), juvenile polyposis syndrome (JPS), Cowden syndrome, Peutz-Jeghers syndrome, MUTYH-associated polyposis (MAP), and Li-Fraumeni syndrome, should be guided by the appropriate, relevant guidelines. In general, endoscopic screening is recommended every 1 to 2 years, starting earlier than the age of diagnosis of the youngest affected relative.

2. Personal history factors: Surveillance colonoscopy is recommended at 1 year, 4 years, and 9 years after curative resection of a CRC with subsequent colonoscopies every 5 years until the burden of surveillance exceeds the benefits.

Recommended surveillance intervals after a complete colonoscopy in patients who have had colon polyps removed completely: Table 11.1-2.

IBD patients with left-sided or extensive ulcerative colitis or with Crohn disease involving more than one-third of the colon should be offered screening colonoscopy after ~8 years of disease duration. The subsequent surveillance intervals of 1 to 3 years are determined by the presence of risk factors for malignancy, such as active inflammation, stricturing, multiple pseudopolyps, history of dysplasia, concomitant primary sclerosing cholangitis, or a family history (FDR) of CRC (see Ulcerative Colitis).

TablesTop

Table 11.1-1. Expected effects of different screening strategies for colorectal cancer

Test

CRC mortality

Advanced-stage CRC

NNS to prevent 1 CRC-related death

gFOBT

RR, 0.82

(95% CI, 0.73-0.92)

RR, 0.92

(95% CI, 0.85-0.99)

NNS, 377

(95% CI, 240-887)

Flexible sigmoidoscopy

RR, 0.74

(95% CI, 0.67-0.82)

RR, 0.73

(95% CI, 0.66-0.82)

NNS, 850

(95% CI, 673-12,052)

CI, confidence interval; CRC, colorectal cancer; gFOBT, guaiac-based fecal occult blood test; NNS, number needed to screen; RR, relative risk.

Adapted from Fitzpatrick-Lewis D, et al. Screening for Colorectal Cancer. Canadian Task Force on Preventive Health Care. https://canadiantaskforce.ca/wp-content/uploads/2016/03/crc-screeningfinal031216.pdf. Updated August 2014. Accessed February 10, 2020.

Table 11.1-2. Recommended surveillance intervals depending on polyp characteristics

Colon polyp characteristics

Surveillance interval

Serrated polyposis syndrome

1 year

≥10 adenomas

<3 years

3-10 tubular adenomas

≥1 tubular adenomas ≥10 mm

Adenoma with high-grade dysplasia

Sessile serrated polyps ≥10 mm

Hyperplastic polyps ≥10 mma

Sessile serrated polyp with dysplasia

Traditional serrated adenoma

3 years

Sessile serrated polyps <10 mm with no dysplasia

5 years

1-2 small (<10 mm) tubular adenomas

5-10 years

Small (<10 mm) hyperplastic polyps in rectum or sigmoid colona

10 years

a The matter of surveillance intervals for hyperplastic polyps ≥10 mm in diameter is controversial. According to the US Multi-Society Task Force on Colorectal Cancer, these lesions should be managed as sessile serrated polyps ≥10 mm, although there is no high-quality evidence to support this.

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