Screening CT Colonography

In the United States, 1 in 17 people will develop colorectal cancer. According to reports from the National Cancer Institute, colorectal cancer is the third most common cancer in US men and women. The overall incidence of colorectal cancer increased until 1985 and then began decreasing at an average rate of 1.6% per year. Approximately 75% of all colorectal cancers occur among persons of average risk, i.e., those without predisposing conditions, such as inflammatory bowel disease, familial adeno-matous polyposis, hereditary nonpolyposis colorec-tal cancer, or a first degree relative with a history of colorectal adenoma or colorectal cancer (Winawer et al. 1991; Ahsan et al. 1998). The age range for development of colon cancer is late 40s to 70s in average-risk patients. The high-risk patient population accounts for approximately 25% of the colorectal cancer incidence in the United States. Deaths from colorectal cancer rank third after lung and prostate cancer in men and third after lung and breast cancer in women.

The proposed natural history of colon cancer in the average-risk patient, as described in the National Polyp Study in 1990, confirmed the expected developmental course of colorectal cancer beginning with an adenomatous polyp, progressing to high-grade dysplasia, and then, frank carcinoma. However, the majority of polyps resected less than 10 mm in size represent hyperplastic polyps and other benign findings. Therefore, the goal of polypectomy should be adenoma resection. Research suggests that there is about a five-year development interval between the stages of adenomatous polyp and adenoma with high-grade dysplasia, and another five-year interval to develop frank cancer (O'brien et al. 1990). The majority of adenomas that will develop into cancer are polypoid or villous in shape (Fig. 2.1). A small proportion of adenomas are so called flat or depressed and have been shown to be difficult to identify on conventional colonoscopy and other colonic imaging modalities. Positive predictive characteristics of an adenoma with increased propensity to develop into cancer are its size and total number of adenomas. Polyps greater than 10 mm in diameter and more that three in number, regardless of their size, have been reported as risk factors for transformation into colorectal cancer through the "adenoma-carcinoma sequence", as described above. Despite prior reports, flat or depressed adenomas do not have an increased risk of developing cancer when compared to the polypoid or villous configurations (Winawer and Zauber 2002). Overall, the literature suggests that the risk of an adenoma, 5 mm or less in greatest dimension, to develop into cancer is significantly low, approximating 0.9% (O'brien et al. 1990).

The goal of colorectal cancer screening is to reduce the morbidity and mortality of colon cancer by early detection and resection of adenomas and cancer (Frazier et al. 2000). The screening guidelines from the National Cancer Institute, and adopted by the American Gastroenterological Association, currently call for screening of the average-risk

asymptomatic patient with an annual digital rectal examination, annual fecal occult blood testing, and flexible sigmoidoscopy every 5 years beginning at age 50. In addition, double contrast barium enema is recommended every 5 years or optical colonoscopy every 10 years beginning at age 50 (Anderson et al. 2002; Winawer et al. 1997). Patients classified as high-risk for developing colorectal cancer undergo screening at a much younger age, as specified by their personal risk factors.

Albeit imperfect with a documented adenoma miss rate ranging from 6 to 27% (depending on the size of the lesion), conventional colonoscopy is still the gold standard for colon cancer screening (Rex et al. 1997). Cancers have also been missed by conventional colonoscopy. A study performed in Canada reported a cancer miss rate of 4% in cancers originating in the right colon (Bressler et al. 2004). Several reasons exist why cancers are missed on conventional colonoscopy: poor bowel prep, slippage of the endoscope around flexures, redundant

Fig. 2.1a-c. Colonic adenoma: a axial CT image demonstrates a soft tissue polypoid lesion located off of the anterior aspect of the ascending colon. CT images (lung window settings) show a discrete polypoid lesion in the ascending colon identified on the reformatted coronal and sagittal images; b reformatted coronal image; c reformatted sagittal image colon, misinterpretation of findings and failure to biopsy (Leaper et al. 2004). A false negative conventional colonoscopy may have serious implications, as patients may not have another colon screening test for a decade.

Conventional colonoscopy is also not without risk to the patient and significant morbidity and mortality has been reported (Garbay et al. 1996). The most common adverse outcome associated with conventional colonoscopy includes hemorrhage and perforation. The rate of perforation of the colon ranges from 0.2 to 0.4% after diagnostic colonoscopy, increases with polypectomy, and approximates 5% with hydrostatic balloon dilatation of colonic strictures (Zubarik et al. 1999).

A landmark multicenter study published by Pickhardt et al. compared CT colonography and conventional colonoscopy in asymptomatic average-risk patient population. As a screening study, comparable adenoma and colorectal cancer detection rates were reported (Pickhardt et al. 2003). In fact, the sensitivity and specificity per patient and per polyp were similar and not statistically different between CTC and conventional colonoscopy for adenomas greater than 10 mm. The sensitivity of CTC for adenomatous polyps was 93.8% for polyps at least 10 mm in diameter, 93.9% for polyps at least 8 mm in diameter, and 88.7% for polyps at least 6 mm in diameter. The sensitivity of conventional colonoscopy for adenomatous polyps was 87.5, 91.5, and 92.3% for the three sizes of polyps, respectively. The specificity of CTC for adenomatous polyps was 96.0% for polyps at least 10 mm in diameter, 92.2% for polyps at least 8 mm in diameter, and 79.6% for polyps at least 6 mm in diameter (Pickhardt et al. 2003).

Detection rates for polyps less than or equal to 5 mm in size are lower and the debate over the significance of these smaller lesions continues. Again, the aim of colorectal cancer screening is to detect cancer and adenomas. With respect to adenomas, the term "advanced adenoma" has been used to describe clinically significant adenomas that have the greatest likelihood to develop into cancer. Current understanding is that adenomas larger or equal to 10 mm reside in this category and should undergo resection. Polyps ranging in size from 5 mm to 9 mm should undergo short-term interval follow-up (van Dam et al. 2004).

The most recent guidelines presented at the 5th Annual International Symposium on Virtual Colonoscopy in Boston, MA for reporting CTC findings are the following: mass lesion, direct referral to surgery; single or multiple polyps >10 mm, direct referral for colonoscopy and polypectomy; single polyp <10 mm but greater than or equal to 6 mm, three year follow up; >3 polyps, each 6 mm -9 mm, referral to colonoscopy and polypectomy; polyps "5 mm, seven year follow up study (Zalis 2004).

CT colonography as a screening tool has the potential to have wider public acceptance compared to conventional colonoscopy. Acceptance of a screening study by a population is multi-factorial. Many physical and psychological barriers to colorectal cancer screening have been described. Surveys have reported patients' reluctance to undergo colorectal cancer screening because of time commitment for the conventional colonoscopy, use of colon cathartics, sedation requirements, prior painful experience and even embarrassment (Rozen and Pignone 2003). CT colonography is relatively fast without the need for sedation or a driver post procedure. Patients have described the post procedure discomfort less for CTC than conventional colonoscopy.

Several studies have shown that patients' acceptance of CTC is greater than conventional colonoscopy or double contrast barium enema (Taylor et al. 2003). Development of minimal bowel prep or prep-less CTC through fecal tagging and electronic cleansing appears to be within reach, thus making a truly prep-less colorectal screening test an attractive possibility (Lefere et al. 2002).

A subset of patients, including the elderly, those with cardiovascular disease, bleeding diathesis and a history of failed colonoscopies, are better suited to undergo CTC for colorectal cancer screening compared to colonoscopy or DCBE.

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