Screening Tests to Detect Colorectal Cancer and Polyps
What is colorectal cancer?
Colorectal cancer (cancer that develops in the colon and/or the rectum) is a disease in which abnormal cells in the colon or rectum divide uncontrollably, ultimately forming a malignant tumor.
Most colorectal cancers begin as a growth, or lesion, in the tissue that lines the inner surface of the colon or rectum. Lesions may appear as raised polyps, or, less commonly, they may appear flat or slightly indented. Raised polyps may be attached to the inner surface of the colon or rectum with a stalk (pedunculated polyps), or they may grow along the surface without a stalk (sessile polyps).
Colorectal polyps are common in people older than 50 years of age, and most do not become cancer. However, a certain type of polyp known as an adenoma is more likely to become a cancer.
Colorectal cancer is the third most common type of non-skin cancer in both men (after prostate cancer and lung cancer) and women (after breast cancer and lung cancer). It is the second leading cause of cancer death in the United States after lung cancer. In 2021, an estimated 149,500 people in the United States will be diagnosed with colorectal cancer and 52,980 people will die from it (1).
Who is at risk for colorectal cancer?
In the United States, colorectal cancer is most common in adults aged 65 to 74. Rates of new colorectal cancer cases are decreasing among adults aged 50 years or older due to an increase in screening and to changes in some risk factors (for example, a decline in smoking) (2). However, incidence is increasing among younger adults (2–4) for reasons that are not known.
An analysis of US population-based cancer registry data from NCI’s Surveillance, Epidemiology, and End Results (SEER) program for 2000 to 2014 shows that, each year over this period, the incidence of colorectal cancer increased 2.7% among 20- to 39-year-olds and 1.7% among 40- to 49-year-olds while decreasing 0.5% among 50- to 59-year-olds, 3.3% among 60- to 69-year-olds, and 3.8% among 70- to 79-year-olds (5).
Although the percentage increases were higher in the younger age groups than the older age groups, fewer colorectal cancers were still diagnosed in younger people than older people (for example, for 2000 to 2014, 22.5 colorectal cancers were diagnosed per 100,000 people aged 40 to 49 years, compared with 128.6 colorectal cancers diagnosed per 100,000 people aged 60 to 69 years).
The major risk factors for colorectal cancer are older age and having certain inherited conditions (such as Lynch syndrome and familial adenomatous polyposis), but several other factors have also been associated with increased risk, including a family history of the disease, excessive alcohol use, obesity, being physically inactive, cigarette smoking, and, possibly, diet.
In addition, people with a history of inflammatory bowel disease (such as ulcerative colitis or Crohn disease) have a higher risk of colorectal cancer than people without such conditions.
What methods are used to screen people for colorectal cancer?
Several screening tests have been developed to help doctors find colorectal cancer before symptoms begin, when it may be more treatable. Some tests also allow adenomas and polyps to be removed before they become cancer. That is, colorectal cancer screening may be a form of cancer prevention in addition to early detection.
The US Preventive Services Task Force (USPSTF) considers the following methods to be acceptable screening tests for colorectal cancer:
- Stool tests. Both polyps and colorectal cancers can bleed, and stool tests check for tiny amounts of blood in feces (stool) that cannot be seen visually. (Blood in stool may also indicate the presence of conditions that are not cancer, such as hemorrhoids.)
Currently, three types of stool tests are approved by the US Food and Drug Administration (FDA) to screen for colorectal cancer: guaiac FOBT (gFOBT); the fecal immunochemical (or immunohistochemical) test (FIT, also known as iFOBT); and multitargeted stool DNA testing (also known as FIT-DNA). With these tests, stool samples are collected by the patient using a kit, and the samples are returned to the doctor. People who have a positive finding with these tests are advised to have a colonoscopy.
- gFOBT uses a chemical to detect heme, a component of the blood protein hemoglobin. Because gFOBT can also detect heme in some foods (for example, red meat), people must avoid certain foods before having this test.
- FIT uses antibodies to detect hemoglobin protein specifically (5, 6). Dietary restrictions are typically not required for FIT.
- FIT-DNA detects hemoglobin, along with certain DNA biomarkers. The DNA comes from cells in the lining of the colon and rectum that are shed and collect in stool as it passes through the large intestine and rectum.
In one study of people who were at average risk of developing colon cancer and had no symptoms of colon problems (11), the FIT-DNA test was more sensitive than the FIT test. However, the FIT-DNA test also was more likely to identify an abnormality when none was actually present (that is, it had more false-positive results, which can lead to unnecessary colonoscopies). Experts generally suggest FIT-DNA testing at least every 3 years (6).
- Sigmoidoscopy. In this test, the rectum and sigmoid colon are examined using a sigmoidoscope, a flexible lighted tube with a lens for viewing and a tool for removing tissue. This instrument is inserted through the anus into the rectum and sigmoid colon as air is pumped into the colon to expand it so the doctor can see the colon lining more clearly. During sigmoidoscopy, abnormal growths in the rectum and sigmoid colon can be removed for analysis (biopsied). The lower colon must be cleared of stool before sigmoidoscopy, but the preparation is not very extensive. People are usually not sedated for this test.
Clinical trials have shown that having sigmoidoscopy lowers the risks of developing and dying from colorectal cancer (12–16). Experts generally recommend sigmoidoscopy every 5 or 10 years for people at average risk who have had a negative test result (10). People who are screened with sigmoidoscopy may also be tested every few years with FIT.
- Colonoscopy. In this test, the rectum and entire colon are examined using a colonoscope, a flexible lighted tube with a lens for viewing and a tool for removing tissue. Like the shorter sigmoidoscope, the colonoscope is inserted through the anus into the rectum and the colon as air is pumped into the colon to expand it so the doctor can see the colon lining more clearly. During colonoscopy, any abnormal growths in the entire colon and the rectum can be removed. The preparation for colonoscopy requires a thorough cleansing of the entire colon before the test. Most patients receive some form of sedation during the test.
A meta-analysis of six observational studies reported that screening with colonoscopy substantially reduces the risks of developing and dying from colorectal cancer (17). Experts recommend colonoscopy every 10 years for people at average risk as long as their test results are negative.
Virtual colonoscopy, also called computed tomographic (CT) colonography, is a screening method that uses special x-ray equipment (a CT scanner) to produce a series of pictures of the colon and the rectum from outside the body. A computer then assembles these pictures into detailed images that can show polyps and other abnormalities. As with standard colonoscopy, a thorough cleansing of the colon is necessary before this test. If polyps or other abnormal growths are found during a virtual colonoscopy, a standard colonoscopy must usually be performed to remove them.
Because virtual colonoscopy also produces images of areas outside the colon and rectum it can lead to the unintentional discovery of medical findings in these areas that require additional follow-up procedures. Virtual colonoscopy may also miss small polyps (18). However, many small polyps may not be likely to become cancer and so taking them out may not be of benefit.
- Other methods. Several other tests to screen for colorectal cancer exist, although these are not generally recommended.
Blood-based DNA test (liquid biopsy). A blood test for an altered gene called SEPT9 is FDA approved to be used to screen adults 50 years or older at average risk for colorectal cancer who have been offered and have a history of not completing colorectal cancer screening. There is no evidence yet that this test can reduce deaths from colorectal cancer.
Double-contrast barium enema (DCBE). This test is another method of visualizing the colon from outside the body. In DCBE, a series of x-ray images of the entire colon and rectum is taken after the patient is given an enema with a barium solution. The barium helps to outline the colon and the rectum on the images. DCBE is rarely used for colorectal cancer screening; however, it may be used for people who cannot undergo standard colonoscopy—for example, because they are at particular risk for complications.
Single-specimen gFOBT done in a doctor's office. Doctors sometimes perform a single-specimen gFOBT on a stool sample collected during a digital rectal examination as part of a routine physical examination. However, this approach has not been shown to be an effective way to screen for colorectal cancer (19).
What do colorectal cancer screening guidelines say about who should have colorectal cancer screening?
Expert medical groups, including the US Preventive Services Task Force (USPSTF) (6), strongly recommend screening for colorectal cancer. Although some details of the recommendations vary, most groups now generally recommend that people at average risk of colorectal cancer get screened at regular intervals beginning at age 45 or 50 (6, 10, 20–22).
The expert medical groups generally recommend that screening continue to age 75; for those aged 76 to 85 years, the decision to screen is based on the individual’s life expectancy, health conditions, and prior screening results.
People who are at increased risk of colorectal cancer because of a family history of colorectal cancer or documented advanced polyps or because they have inflammatory bowel disease or certain inherited conditions (such as Lynch syndrome and familial adenomatous polyposis) may be advised to start screening earlier and/or have more frequent screening.
How can people and their health care providers decide which colorectal cancer screening test(s) to use?
It is important to have colorectal cancer screening. Different tests have different advantages and disadvantages, and people should talk with their health care provider about which test is best for them.
An individual's decision about which test to have may depend on:
- the person’s age, medical history, family history, and general health
- potential harms of the test
- the preparation required for the test
- whether sedation may be needed for the test
- the follow-up care needed after the test
- the convenience of the test
- the cost of the test and the availability of insurance coverage
The table below summarizes key features of the different colorectal screening tests that people may want to consider when choosing a test.
|Test||Diet and medication changes before test?||Invasive procedure?||Preparation (colon cleansing) needed?||Sedation needed?||Test frequency||Additional considerations|
|Stool tests||Yes for gFOBT, no for FIT or FIT-DNA||No||No||No||Every year to every 3 years, depending on the test||
|Sigmoidoscopy||Yes||Yes||Yes (less extensive than for colonoscopy)||Usually no||Every 5 to 10 years, possibly with more frequent FIT||
|Colonoscopy||Yes||Yes||Yes||Yes||Every 10 years||
|Virtual colonoscopy||No||No||Yes||No||Every 5 years||
Does health insurance pay for colorectal cancer screening?
Colorectal cancer screening is a preventive service that the Health Insurance Marketplace and many other health plans are required to cover. Medicare covers several colorectal cancer screening tests for its beneficiaries. However, Medicare and some insurance companies currently do not pay for the costs of virtual colonoscopy. Specific information about Medicare benefits for colorectal cancer screening is available on the Medicare website.
A colonoscopy to follow up on a screening test with a positive result, such as an abnormal stool test or even a lesion detected on a screening colonoscopy, is considered to be a diagnostic exam and may not be covered (or not covered as fully as a screening colonoscopy). Some insurers consider a screening colonoscopy that reveals a polyp that must be removed to be a diagnostic exam and charge accordingly. People should check with their health insurance provider to determine their colorectal cancer screening coverage and what their out-of-pocket expenses may be if the test finds an abnormality that needs to be followed up.
What happens if a colorectal cancer screening test finds an abnormality?
If a screening test finds an abnormality (a lesion or tumor), additional tests may be needed. These tests most often include a colonoscopy if it has not already been done, such as in the case of stool blood testing. If an abnormality is found during sigmoidoscopy, a biopsy or polypectomy may be performed during the test, and a follow-up colonoscopy may be recommended. If an abnormality is found during a standard colonoscopy, a biopsy or polypectomy may be performed during the test to determine whether cancer is present. If an abnormality is detected during virtual colonoscopy, the patient will be referred for a standard colonoscopy.
What new tests are being developed for colorectal cancer screening?
Among new approaches to colorectal cancer screening that are being explored are ways to improve visualization of the colon. One technique is capsule colonoscopy (also called capsule endoscopy), in which a person swallows a pill-like capsule that contains a tiny wireless camera. The camera takes pictures of the inside of the digestive tract and sends them to a small recorder that is worn on the patient’s waist or shoulder. The pictures are then viewed on a computer by the doctor to check for signs of disease. The capsule passes out of the body during a bowel movement. Cleansing of the colon is still necessary before this test. This method is currently approved for patients with an incomplete colonoscopy and for detection of colon polyps in patients with evidence of lower GI bleeding but not as a stand-alone screening test.
One new approach to colorectal cancer screening is to look for cells released by colorectal polyps and tumors into the bloodstream (24). These so-called circulating tumor cells (CTCs) are rare, however. Researchers have developed an ultrasensitive antibody-linked CTC detection technology to capture colorectal epithelial cells associated with colorectal tumors and adenomas in blood samples (25). In a proof-of-concept study, this blood-based CTC test was able to distinguish between patients with colorectal adenomas or cancer and people without cancer (26).
Researchers have also identified small molecules, called metabolites, in urine that may signal the presence of colorectal polyps and tumors (27, 28). In a clinical study, a metabolomic-based urine test was better able to identify patients with adenomas than stool-based tests (29).
Researchers are also trying to improve the sensitivity of stool-based screening for detecting advanced adenomatous polyps, which can potentially become colorectal cancer, by testing for the presence of multiple biomarkers. For example, measuring three protein biomarkers in stool—hemoglobin, calprotectin, and serpin family F member 2—improved the ability of FIT to detect advanced lesions (including colorectal cancer) by 35% without reducing its specificity (30).
Information about ongoing clinical trials that are studying methods for colorectal cancer screening can be found in NCI’s clinical trials database. You may also contact NCI’s Cancer Information Service at 1-800-4-CANCER (1-800-422-6237) for assistance with searching the clinical trials database.