Advancements in Screening for Colorectal Cancer

Posted on February 5th, 2009 by

Although there is no doubt that screening for colorectal cancer saves lives, only about half of all Americans undergo the recommended screening for the disease. This low compliance rate to screening is perhaps the single greatest reason why colorectal cancer remains the second-leading cause of cancer-related deaths in the United States. This is despite the facts that colorectal cancer is one of the most treatable forms of cancer if detected early and that highly effective screening measures can completely prevent the disease from developing (or lead to successful treatment in its earliest stages) when integrated into standard medical guidelines.

So, why the low compliance rate with screening? At this point the invasiveness of the screening methods and a lack of awareness about the need for screening are believed to be the two greatest deterrents to screening for colorectal cancer. The good news is that the medical community is addressing both these factors to increase screening compliance and reduce the number of lives claimed by the disease each year.

What Are the Current Screening Guidelines?
Screening guidelines recommend that all individuals age 50 years and older initiate screening for colorectal cancer as should younger individuals who have a family history of colorectal cancer or are otherwise considered at high risk of developing the disease. According to recent recommendations from the U.S. Preventive Services Task Force (USPSTF), screening should continue at least through the age of 75. Individuals between the ages of 76 and 85 may wish to talk with their physician about the need for continued screening; after the age of 85, colorectal cancer screening is unlikely to provide a benefit.
According to the American Cancer Society (ACS), screening methods that have been proven effective in clinical trials include colonoscopy (the preferred and most accurate screening procedure for the early diagnosis of colorectal cancer), virtual colonoscopy, sigmoidoscopy, fecal occult blood test (FOBT), double-contrast barium enema, and detection of DNA mutations in the stool (sDNA).2 Depending on the results of the specific screening method, follow-up schedules vary.

What Is a Colonoscopy?
A colonoscopy is a procedure in which a thin, flexible tube—or scope—with a built-in camera is placed through the patient’s rectum and physically advanced through the entire large intestine. The day prior to a colonoscopy, patients undergo a “bowel prep,” which may include laxatives and enemas. Immediately before the procedure, patients may receive relaxants or pain medication, although they tend to be awake throughout the test. When patients are fully prepped, air is placed into the colon as the tube advances so that the colon is expanded and the physician is able to view on a video monitor real-time pictures of all sides of the lining of the colon. The physician is able to identify areas that look suspicious for cancer or other diseases, and biopsies or the removal of polyps (small growths within the colon that can turn cancerous) may be performed during the procedure for laboratory examination. Patients are often groggy for a few hours following a colonoscopy and are not allowed to drive themselves home after the procedure.

What Is a Sigmoidoscopy?
A sigmoidoscopy uses the same general type of scope as in a colonoscopy, though it is much shorter and only exams the left side of the colon (about 40 percent of the total colonic length). The scope is inserted through the rectum and advanced through just the lower portion (approximately 2 feet) of the large intestine. Often a sigmoidoscopy is performed during an office visit; and although air is also placed into the colon as the scope is advanced, patients typically do not require sedation or pain medication. As with a colonoscopy, the physician is able to directly view the lower portion of the lining of the colon and remove suspicious areas, such as polyps. Although patients may be advised to take a laxative or an over-the-counter enema prior to a sigmoidoscopy, the bowel prep tends to be significantly less aggressive than that required for a colonoscopy, and patients are able to drive themselves home from their appointment. If polyps or suspicious areas are detected, patients are often referred to undergo a subsequent colonoscopy.

What Is an FOBT?
In a fecal occult blood test, a stool sample is tested for the presence of small amounts of blood in the stool, as that may indicate the presence of colorectal cancer. If an FOBT result is positive (there is blood in the stool), a patient will often be referred for a subsequent colonoscopy. Patients are often sent home with a kit and instructions for the FOBT, which is then returned to the laboratory or clinic for results. The American Cancer Society (ACS) also includes the fecal immunohistochemical test (FIT) within its guidelines for colorectal cancer screening. The FIT is a type of FOBT, which also tests for the presence of blood in the stool.

Virtual Colonoscopy
One of the most promising new advances in screening for colorectal cancer is computed tomography colonography (CTC), also referred to as virtual colonoscopy. A CTC involves the use of a computer program to develop three-dimensional images of the colon via X-rays, without the need for a scope. The hope among healthcare providers is that patients will not consider a CTC as invasive as a standard colonoscopy and will therefore be more willing to undergo screening. Similar to a standard colonoscopy, a CTC still requires bowel prep the day before the procedure as well as the infusion of air into the colon. The images of the colon, however, are obtained from X-ray machines outside the body. One drawback to a CTC is that the physician is unable to remove areas of suspicion, such as polyps, during the procedure, and patients with abnormal findings must undergo a subsequent colonoscopy.
The most recent results evaluating CTC for screening of colorectal cancer were published in the New England Journal of Medicine. This trial was conducted by researchers from the Mayo Clinic to further explore the accuracy of CTC compared with standard colonoscopy among patients who did not exhibit any signs of colorectal cancer. This trial at 15 different medical centers included 2,600 individuals 50 years or older who first underwent a CTC followed by a standard colonoscopy.

  • CTC accurately identified 90 percent of cancers measuring 10 mm (millimeters) or more in diameter.
  • CTC detected only 78 percent of smaller cancers (6 mm or greater).

CTC appears to be quite accurate in identifying larger masses (10 mm or greater) within the colon, which are more highly associated with the development of colorectal cancer than are smaller masses. Its use in identifying smaller masses is less accurate, however; and although smaller masses are not as often associated with being cancerous, their removal may prevent the development of cancer altogether. Nevertheless, an overall benefit of CTC may be realized if compliance rates are improved over standard colonoscopy. Future improvements for CTC in identifying smaller masses may include more training for the radiologists reading the CTC reports.
While CTC is currently included in the ACS guidelines for the screening of colorectal cancer, it should be noted that recent USPSTF recommendations state that there is still insufficient evidence to fully assess the risks and benefits of CTC. Patients should always be sure to speak with their healthcare provider regarding their individual risks and benefits of the different types of screening for colorectal cancer.

Stool DNA Testing (sDNA)
SDNA testing was recently added to the American Cancer Society–US Multi-Society Task Force (ACS-MSTF) Guidelines. This simple, non-invasive test looks for abnormalities known to be associated with colon cancers and colon polyps in DNA shed into the stool sample. Unlike bleeding (FOBT/FIT), which is not directly related to cancer development, often does not occur in early lesions, and may only be present intermittently, if at all, in stool samples, DNA abnormalities are fundamental to the development of all colorectal cancer,. Cells from the lining of the colon—and especially from cancers–are constantly shed in stools, where they release their DNA. Laboratory tests can detect this abnormal DNA in a stool sample. If an abnormality is detected, the patient is then referred for a colonoscopy for final diagnosis.

Unlike FOBT, sDNA testing has been designed to increase compliance with colorectal cancer screening by providing a safe, simple and non-invasive approach using a single stool specimen that requires no stool handling or manipulation by the person being screened. sDNA is designed for people who are unwilling or unable to have colonoscopy. Early data indicates that over 50 percent of people who use sDNA testing had never been screened before and that over 90 percent were very satisfied/satisfied with the collection process and were likely to use the test again in the future. 13 Currently, an sDNA test that relies on a single genetic marker is offered by Laboratory Corporation of America, under the name of ColoSure TM11
The sDNA test is constantly improving as more information is discovered about the genetic markers of colorectal cancer allowing for more accurate and comprehensive test panels to be prepared. Studies of a two marker sDNA test have shown the identification of over 80 percent of colorectal cancers including both early and later stages as well as the advanced polyps most likely to become malignant (high-grade dysplasia)12. The development of highly sensitive techniques to identify even single abnormal DNA molecules in stool specimens could lead to cancer detection in over 90 percent of cases.15
As with CTC imaging, the ACS and USPSTF differ in their recommendation of sDNA testing; the test is included in the ACS guidelines, but the USPSTF notes that there is still insufficient evidence to fully assess the risks and benefits. In all cases, patients should speak with their healthcare provider about which type of screening best suits their needs and personal history.

Double-contrast Barium Enema
Although a double-contrast barium enema is not widely used as a standard screening method for colorectal cancer, it remains an option within the NCI and ACS guidelines and may still be used for some patients. The procedure involves bowel prep followed by an enema that is filled with a chalky substance that can be viewed on an X-ray. The X-ray images of the colon can reveal abnormalities, which are then confirmed with a subsequent colonoscopy.

From the bowel prep to the idea of the procedures themselves, it is perhaps not surprising that individuals come up with many creative excuses to postpone screening, particularly if they have no symptoms. Colorectal cancer is most curable prior to any symptoms, however, so delaying screening can come with the uncompromising consequence of a diagnosis of advanced cancer and, ultimately, death from the disease. Healthcare providers continue to explore novel screening methods that not only are accurate and effective but that will also seem less daunting to patients.

Advances in Screening
Clinical trials are ongoing to evaluate “new and improved” screening based on the standard screening methods. For example, improvements in bowel prep timing and measures, improvements to the scopes used for colonoscopies, and sedation measures—all are designed with the intent of reducing the discomfort associated with the procedures. Stool DNA tests to more accurately identify DNA mutations and alterations known to be associated with precancerous adenomas (those polyps most likely to become cancer) are also under way. In addition to these, novel methods of screening are being evaluated. The following screening procedures are still investigative in nature and have not been widely accepted as standard screening measures for colorectal cancer, but they provide hope for the future of colorectal cancer screening.

Gene Tests
The testing of specific genes that may predispose an individual to a higher risk of developing colorectal cancer is also under way. This is different from testing for DNA mutations found in a stool sample, which look for signs of existing colorectal cancer and are designed for general screening of the population of people over age 50. ColonSentry™ , a test created to determine predisposition to cancer, analyzes the expression (activity) of seven different genes in a blood sample and stratifies a patient’s risk of having colorectal cancer. Patients who are considered at high risk of developing colorectal cancer would be referred to an immediate subsequent screening such as a colonoscopy, whereas those with a low risk may defer screening to a future time.

Use of Light
Researchers are evaluating ways to use different spectrums of light to identify cells within the colon that display abnormal activity, such as cancer cells, during colonoscopy. One technique is referred to as photodynamic diagnosis, which is already being used to diagnose and treat some types of cancer such as skin cancer. Photodynamic diagnosis includes the use of a photosensitive drug, which selectively collects in abnormal cells such as cancer cells. The drug is activated when a particular wavelength, or color of light—in this case blue—is applied to the area. The activation of the drug causes the cancer cells to turn a certain color (red) that can be easily visualized and might otherwise have been missed through other screening methods.
Another use of light for colorectal cancer screening in the early stages of clinical studies is one that uses the properties of light scattering. This method of screening uses two technologies: four-dimensional elastic light-scattering fingerprinting (4D-ELF) and low-coherence enhanced backscattering spectroscopy (LCEBS). In essence, this method includes a fiber-optic probe about the size of a pen that is inserted into the rectum. The probe emits light that shines on the tissues of the colon. The scattering of light is affected by cellular abnormalities, and the scattered pattern is returned from the tissues in the colon to the probe. The pattern of light is then analyzed on a computer, which can detect nanoarchitecture, or changes in cells that may be indicative of the development of cancer even before a polyp is formed. This optical technique could be performed during an office visit and would not require the same bowel prep as colonoscopy.

Screening Schedules
In addition to new techniques for the screening of colorectal cancer, researchers are evaluating optimal schedules for specific screening tests among different subsets of patients.
Researchers from Indianapolis recently conducted a clinical trial to evaluate the time interval between repeat colonoscopies among patients with normal results from an initial colonoscopy. This trial included 1,256 individuals who underwent rescreening at an average of 5.34 years following their original colonoscopy.

  • None of these patients had colorectal cancer identified on the follow-up colonoscopy.
  • 16 percent of patients had non-cancerous tumors on repeat colonoscopy; however, advanced non-cancerous tumors were found in only 1.3 percent of patients.

The researchers concluded: “Our findings support a rescreening interval of five years or longer after a normal colonoscopic examination.”8
In addition, researchers in South Australia from the Flinders Centre for Innovation in Cancer conducted a clinical trial that included individuals with a family or personal history of colorectal cancer. The study had 1,071 patients who underwent FIT screening annually between required colonoscopies and 665 patients who did not undergo the annual FIT screening. Patients who underwent annual FIT screening had colorectal cancer detected an average of 26.5 months earlier than if they would have just undergone the scheduled colonoscopies. Interim results indicated that annual FIT screening identified 86 percent of colorectal cancers in this study and may potentially provide an easy screening measure between scheduled colonoscopies for those patients who are at high risk of developing the disease.9

The paradox of colorectal cancer remains: it is easily treatable in early stages and has highly effective screening methods that can prevent the disease altogether, but it remains the second-leading cause of cancer-related deaths in this country. Researchers are hopeful that with novel screening methods resulting in higher compliance rates, the story of colorectal cancer will ultimately parallel that of cervical cancer in that deaths from the disease will be virtually nonexistent in this country as screening becomes commonplace. Every individual should speak with their healthcare provider regarding their individual risks and benefits of the different types of screening for colorectal cancer.

. Shapiro JA, Seeff LC, Thompson TD, et al. Colorectal cancer test use from the 2005 National Health Interview Survey. Cancer Epidemiology, Biomarkers, and Prevention. 2008;17(7)1623-30.

The U.S. Preventive Services Task Force recommendation on Screening for Colorectal Cancer . Available at: Accessed October 24, 2008.

. Can Colorectal Polyps and Cancer Be Found Early? American Cancer Society Web site. Available at: Accessed September 26, 2008.

. Johnson CD, Chen MH, Toledano AY, et al. Accuracy of CT colonography for detection of large adenomas and cancers. New England Journal of Medicine. 2008;359(12):1207-17.

The U.S. Preventive Services Task Force recommendation on Screening for Colorectal Cancer . Available at: Accessed October 24, 2008.

. GeneNews Launches World’s First Blood Test for Colorectal Cancer Screening. GeneNews Web site. Available at: Accessed September 26, 2008.

. PhotoCure ASA. Excellent Clinical Trial Data from Photocure’s Photodynamic Diagnostic Lumacan [press release]. Newsdesk Web site. Available at: Accessed September 26, 2008.

. New Technology May Detect Colon Cancer Earlier. Northwestern University Web site. Available at: Accessed September 26, 2008.

. Imperiale TF, Glowinski EA, Lin-Cooper C, Larkin GN, Rogge JD, Ransohoff DF, et al. Five-year risk of colorectal neoplasia after negative screening colonoscopy. New England Journal of Medicine. 2008;359(12):1218-24.

9. Chow E, et al. The value of interval fecal occult blood testing in Colonoscopy-based Surveillance Program (CSP) for people at increased risk for colorectal cancer. Paper presented at: 2008 Annual Digestive Disease Week; May 18-21, 2008; San Diego, California. Abstract  620.

10. DNA Direct Announces Availability Of ColoSure(TM) Colorectal Cancer Screening Test [press release]. DNA Direct, Inc.; October 2, 2008. Available at: Accessed October 24, 2008.

11. LabCorp Announces Availability of ColoSure(TM) [press release]. Laboratory Corporation of America. July 14, 2008 Available at: – 63k . Accessed October 24, 2008.

12. Itzkowitz SH, Brand R, Jandorf L, Durkee K, Millholland J, Rabenek L, Schroy PC, Sontag S, Johnson D, Markowitz S, Pazat L, Berger BM. A simplified noninvasive stool DNA test for colorectal cancer detection. Am. J Gastro 2008;103:1-9.

13. Berger BM, Schroy PC, Rosenberg JL et al, Colorectal cancer screening using stool DNA analysis in clinical practice: Early clinical experience with respect to patient acceptance and colonoscopic follow-up of abnormal tests. Clin Colorectal Cancer 2006;5:338-43.

14. Itzkowitz SH, Jandorf L, Brand R, Rabanek L, Schroy PC, Sontag S, Johnson D, Skoletsky J, Durkee K, Markowitz S, Shuber A. Improved fecal DNA test for colorectal cancer screening. Clin Gastro Hep 2007;5(1):111-117.

15. Diehl F, Schmidt K, Durkee KH, More KJ, Goodman SN, Shuber AP, Kinzler K, Vogelstein B. Analysis of mutations in DNA isolated from plasma and stool of colorectal cancer patients. Gastroenterology 2008;135:489-498.

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Tags: Colon Cancer

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