**7. Tests for colorectal cancer screening**

Tests for CRC include: colonoscopy, flexible sigmoidoscopy (FS), virtual colonoscopy and faecal occult blood testing (FOBt).

#### **7.1. Faecal Occult Blood testing (FOBt)**

FOBt has been used widely in CRC screening for several decades. Screening at age 50 for asymptomatic persons who are at average risk with annual and biennial FOBt has been shown in multiple randomized trails to reduce CRC incidence and mortality rates [49].

FOBt can detect occult blood in a small amount of stool sample. It is cheap, non-invasive and easily performed at home. FOBt is based on the propensity of CRC and adenomas to bleed microscopically.

There are two different types of FOBT, guaiac FOBT (gFOBT) and immunochemical FOBT (iFOBT). The gFOBT uses a guaiac-impregnated card to detect heme. The basis of the test involves the detection of the peroxidase activity of heme when a hydrogen peroxide developer is added. Therefore, the presence of any other peroxidases, e.g. from fruit/ vegetables, can result in a false positive test, as can the presence of heme in red meat. There can also be bleeding within the intestine for other reasons, again resulting in false positive results. False negative results can occur due to the irregular nature of the bleeding from the tumor; several samples are usually requested to attempt to overcome this problem [50]. The sensitivity of gFOBT is about only 50% of cancers will be picked up in population screening (figure 6).

iFOBT test have been developed which specifically detect the hemoglobin in human feces by antibodies and is widely available now [51]. It is more sensitive and specific for human hemoglobin than gFOBT and thus does not require dietary or drug restriction. However, iFOBT is more expensive than gFOBT and the high analytical sensitivity of most of the commercially available tests results in a greater number of participants requiring colonoscopy and a greater false positive rate [54]. However, recent developments in quantitative iFOBT may overcome this problem, asthe trigger for investigation can be set at any concentration of fecal hemoglobin. Clinical trials have shown that persons with positive occult-blood tests have a risk of cancer that is three to four times as high as that among persons with negative tests, and that colonoscopy should be recommended for persons with these positive tests. In a recent study (Quintero et al) it has been shown that both iFOBT and colonoscopy are effective for detecting colorectal cancer but iFOBT is less effective for early detection of premalignant lesions (adenomas) than colonoscopy or sigmoidoscopy [57]. However, comparative studies have shown that iFOBT is more accurate than the gFOBT for the detection of colorectal cancer and advanced adenomas and this new test is now recommended as the first-choice fecal occult blood test in colorectal-cancer screening.

#### **7.2. Flexible sigmoidoscopy**

**6. Who is at risk of developing colorectal cancer**

16 Colonoscopy and Colorectal Cancer Screening - Future Directions

**7. Tests for colorectal cancer screening**

faecal occult blood testing (FOBt).

microscopically.

**7.1. Faecal Occult Blood testing (FOBt)**

There is strong tendency that countries with an obviously rising CRC incidence are more "Westernized" in lifestyle, especially in dietary habits, with increased consumption of high fat and protein but less fiber in diet. The change is more evident in urban areas than rural areas of the same country. Most of CRC is sporadic, i.e., caused by the interaction of genetic and environmentalfactorsviatheadenomacarcinomasequence,andcancermaytakeuptotenyears to develop in this way. Adenomas are more common with age, and one in four of the popula‐ tion aged over 50 will develop one or more polyps, with 10% of these polyps progressing to cancer over time.The most common indicator of high risk is a first-degree relative with CRC.

Tests for CRC include: colonoscopy, flexible sigmoidoscopy (FS), virtual colonoscopy and

FOBt has been used widely in CRC screening for several decades. Screening at age 50 for asymptomatic persons who are at average risk with annual and biennial FOBt has been shown

FOBt can detect occult blood in a small amount of stool sample. It is cheap, non-invasive and easily performed at home. FOBt is based on the propensity of CRC and adenomas to bleed

There are two different types of FOBT, guaiac FOBT (gFOBT) and immunochemical FOBT (iFOBT). The gFOBT uses a guaiac-impregnated card to detect heme. The basis of the test involves the detection of the peroxidase activity of heme when a hydrogen peroxide developer is added. Therefore, the presence of any other peroxidases, e.g. from fruit/ vegetables, can result in a false positive test, as can the presence of heme in red meat. There can also be bleeding within the intestine for other reasons, again resulting in false positive results. False negative results can occur due to the irregular nature of the bleeding from the tumor; several samples are usually requested to attempt to overcome this problem [50]. The sensitivity of gFOBT is

iFOBT test have been developed which specifically detect the hemoglobin in human feces by antibodies and is widely available now [51]. It is more sensitive and specific for human hemoglobin than gFOBT and thus does not require dietary or drug restriction. However, iFOBT is more expensive than gFOBT and the high analytical sensitivity of most of the commercially available tests results in a greater number of participants requiring colonoscopy and a greater false positive rate [54]. However, recent developments in quantitative iFOBT may overcome this problem, asthe trigger for investigation can be set at any concentration of fecal hemoglobin. Clinical trials have shown that persons with positive occult-blood tests have

in multiple randomized trails to reduce CRC incidence and mortality rates [49].

about only 50% of cancers will be picked up in population screening (figure 6).

Flexible sigmoidoscopy has also been used as a screening tool for CRC detection, as half of all cancers are seen in the rectum or sigmoid colon. There have been several studies suggesting benefit from flexible sigmoidoscopy, and their data suggest that flexible sigmoidoscopy would be an effective screening tool. Flexible sigmoidoscopy as an alternative to colonoscopy has the advantage that no oral bowel preparation is required, as the subject uses an enema that can be taken at home.The procedure is quick, requires no sedation and examines the left colon, which is the site of 75 per cent of all colorectal neoplasia. If CO2 insufflation is used, adenomas can be resected at the initial screening examination. This procedure does not, however, examine the right colon. For many clinicians and patients, colonoscopy is more appealing than flexible sigmoidoscopy because patients can be sedated and undergo a complete colon examination with polypectomy.

#### **7.3. Virtual colonoscopy**

Virtual colonoscopy, or computed tomography colonography (CTC), is another modality used to examine the colon. It has been suggested that this examination has fewer complications and increased patient satisfaction when compared to colonoscopy, but with similar sensitivity and specificity for the detection of pathology. There is no requirement for sedation and it has the advantage of detecting extracolonic pathology. It does, however, still require bowel prepara‐ tion and colonic insufflation with CO2, the latter still causing discomfort. Furthermore, it is not therapeutic and the lesions detected require endoscopic evaluation and resection.

**8. Conclusions and recommendations**

Kouklakis S. Georgios and Asimenia D. Bampali

Cancer Inst 2011; 103:714.

Nancy N. Baxter and Jose G. Guillem

N9741. *J Clin Oncol*. Dec 10 2008;26(35):5721-7.

Medical School Democritus, University of Thrace, Greece

screening.

**Author details**

**References**

85:1670.

Although there are several methods available for CRC screening, none is optimal. Patients at average risk for CRC should begin screening at age 50 with either annual FOBT, flexible sigmoidoscopy every 5 years or colonoscopy every 10 years. Evidence does not show any strategy as optimal, so clinicians should discuss the advantages and disadvantages of the various screening techniques with patients. Patients with a family history of CRC or adenomas or a personal history of high-risk polyps or inflammatory bowel disease should begin screening earlier (figure 7). Routine screening in persons older than 75 years of age is not recommended. Life expectancy, rather than age alone, should guide decisions about when to stop CRC

Colorectal Cancer

19

http://dx.doi.org/10.5772/53524

[1] Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin 2011; 61:69. [2] Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin 2012; 62:10. [3] Kohler BA, Ward E, McCarthy BJ, et al. Annual report to the nation on the status of cancer, 1975-2007, featuring tumors of the brain and other nervous system. J Natl

[4] Davis DM, Marcet JE, Frattini JC, et al. Is it time to lower the recommended screening

[5] Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010; 60:277. [6] Troisi RJ, Freedman AN, Devesa SS. Incidence of colorectal carcinoma in the U.S.: an update of trends by gender, race, age, subsite, and stage, 1975-1994. Cancer 1999;

[8] Colorectal Cancer: Epidemiology, Etiology, and Molecular Basis. Harvey G Moore,

[9] Sanoff HK, Sargent DJ, Campbell ME, et al. Five-year data and prognostic factor analysis of oxaliplatin and irinotecan combinations for advanced colorectal cancer:

[7] Jessup JM, McGinnis LS, Steele GD Jr, et al. The National Cancer Data Base.

age for colorectal cancer? J Am Coll Surg 2011; 213:352.

#### **7.4. Colonoscopy**

Colonoscopy is the gold standard investigation for the diagnosis of CRC. It is highly sensitive and specific for detecting both cancers and adenomas of at least 1 cm in diameter and has the added benefit not only of providing tissue for diagnostic purposes, but also affords the opportunity of removing adenomas by polypectomy and hence preventing colorectal cancer (CRC). Several large cohort studies show that among patients at average risk who undergo screening colonoscopy, 0.5 to 1.0% have colon cancer and 5 to 10% have advanced neoplasia that can be removed. Several studies have shown that among patients with an adenoma that is detected and removed at screening colonoscopy, colorectal cancer may develop in 0.3 to 0.9% within 3 to 5 years after screening. In a recent study (Zauber et al) it has been evaluated the long -term effect of colonoscopic polypectomy on mortality from colorectal cancer. According to the results of this study, the endoscopic removal of adenomas ends in reduced mortality from colorectal cancer [56]. To sum up, this procedure is considered the most accurate test for early detection and prevention of colorectal cancer as it markedly reduces the risk of CRC and death. Unfortunately, there are limitations to its use as a screening modality on a population level, although it may be the ideal choice of examination for an individual. Colonoscopy is invasive and time consuming,and requires full bowel preparation; the complication rate, although low, may still be unacceptable within a screening population.

**Figure 7.** British Society of Gastroenterology guidelines for follow-up of adenoma removal.
