Colorectal Cancer Screening
Judy Yee
Cancer of the colorectum is the third most common cancer in men and women in the United States. Colorectal cancer is the second leading cause of cancer-related deaths in this country. The estimated number of new cases and deaths due to colorectal cancer in 2007 are 153,790 and 52,180 respectively.1 Colorectal cancer represents approximately 11% of new cancer cases and approximately 10% of all deaths due to cancer.1 There is an overall lifetime risk of 6% for the development of colorectal cancer with a lifetime risk of 2.5% for dying from this malignancy.2
The incidence of colorectal cancer increases with increasing age. Overall, this malignancy affects men and women equally.3 It is particularly important to remember that most cases of colorectal carcinoma (approximately 75%) occur sporadically in average-risk patients who have no known risk factors.3
There have been favorable trends noted with a general decrease in both colorectal cancer incidence and mortality rates since the 1970s. Colorectal cancer incidence rates have been found to stabilize since the mid 1990s.1 Five-year survival rates have increased by approximately 12% over the last 20 years.1,4 Improved survival rates are at least in part related to increased screening for polyps, with their subsequent removal preventing progression to malignancy. Colorectal cancers are also diagnosed at an earlier stage when they are more likely curable and treatments have also improved. Although these trends are encouraging, the total impact of earlier diagnosis and treatment on this disease has been limited. Currently, only approximately 39% of cases of colorectal carcinoma are diagnosed when the disease is localized within the bowel wall.1 Approximately 20% of patients will already have distant metastases from colorectal carcinoma at the time of the initial diagnosis of the disease.1,4
Colorectal cancer is predominantly a preventable disease if precursor adenomatous polyps are identified and then removed. However, current screening rates in the United States remain low. In one study, only 17% of individuals aged 50 or older had undergone fecal occult blood testing (FOBT) in the previous year and only 9% had undergone sigmoidoscopy in the previous 3 years.5 National Health Interview Surveys found that the use of FOBT increased from 18% for men and 21% for women in 1987 to 29% for men and 26% for women in 1998.6
This chapter discusses the epidemiology, staging, and pathophysiology of colorectal cancer as well as risk factors for development. The advantages and disadvantages of the currently recommended available screening tests for colorectal carcinoma are described. Knowledge of the characteristics of this malignancy as well as the current tools used to detect it are necessary for understanding the role of virtual colonoscopy (computed tomographic colonography) in screening for colorectal cancer.
STAGING
Staging of colorectal cancer is related to the extent of tumor through the layers of the colon wall, extension outside the colon locally, and the degree of metastases to lymph nodes and other organs. Survival rates correlate directly with the stage of the disease. There are several systems used for staging colorectal cancer including the Dukes’, Astler-Coller, and TNM/American Joint Committee on Cancer (AJCC) systems. The Dukes and the Astler-Coller systems stage colorectal carcinoma using A through C, with the Astler-Coller system being more complex with an additional stage D and the use of subdivisions. The TNM/AJCC system is the most detailed staging system and delineates the extent of the primary tumor (T), the involvement of lymph nodes (N), and whether distant metastasis is present or not (M). The T categories of colorectal carcinoma detail the extent of spread of tumor through the layers of the bowel wall starting with the innermost layer to the outermost layer in the following order: mucosa, submucosa, muscularis propria, subserosa, and serosa. The N categories describe the spread of tumor to lymph nodes and if present, the number of involved lymph nodes. The M categories tell whether there is spread of malignancy to distant sites such as the liver, lungs, or nonregional lymph nodes (see Tables 1.1 and 1.2).7
TABLE 1.1 TNM Classification of Colorectal Carcinoma | ||||||||||||||||||||||||||||||||||
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PATHOPHYSIOLOGY
Most colorectal malignancies are adenocarcinomas and arise from precursor tubular adenomatous polyps.8 Histologically polyps with a villous component have an even higher chance of transforming into a malignancy. It can take a relatively long time of up to 10 years for an adenomatous polyp, particularly those smaller than 10 mm in diameter, to transition into an invasive malignancy.2 Therefore, colorectal cancer is a malignancy that is ideally suited for screening with the intent to prevent its occurrence by removing the precursor lesion. The prevalence of adenomatous polyps increases with increasing age. At age 50, approximately 25% of individuals will have an adenomatous polyp of any size. By age 80, approximately 50% to 60% of individuals will harbor an adenomatous polyp.2 Overall, only 3% to 5% of individuals with adenomatous polyps will develop malignancy.9 Although it is difficult to know exactly which adenomas will undergo malignant transformation, it has been found that the risk of malignancy is related to polyp size. Only approximately 1% of adenomas smaller than 10 mm are found to contain malignancy.10 However, adenomatous polyps between 10 and 15 mm in size have an up to 15% chance of transforming into a malignancy within 10 years11 (see Table 1.3).
TABLE 1.2 Stage Grouping of Colorectal Carcinoma | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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RISK FACTORS
There are known risk factors for the development of colorectal carcinoma. A large majority of cases of colorectal carcinoma occur in individuals aged 50 and older. Therefore, screening for colorectal cancer in asymptomatic individuals with no known risks for colorectal carcinoma is recommended starting at age 50.
Familial factors associated with an increased risk for the development of colorectal carcinoma include familial adenomatous polyposis (FAP) and Gardner syndrome. Hereditary nonpolyposis colorectal carcinoma (HNPCC) is another familial risk factor.12 Increased risk for developing colorectal carcinoma has also been found in the Ashkenazi Jewish population.
A personal or close family history of adenomatous polyps or colorectal carcinoma will increase an individual’s risk for subsequent development of this malignancy. First-degree relatives of patients with colonic adenomas have been found to carry a 1.3- to 1.6-fold increased risk for the development of colorectal carcinoma.13 Studies have also found that the risk of colorectal cancer in
family members is increased even further when patients are diagnosed before the age of 60.14,15 Individuals with a first-degree relative with colorectal cancer have a twofold to fourfold increased risk for the development of colorectal carcinoma.16 In women, a personal history of ovarian, endometrial, or breast carcinoma is associated with an increased incidence of colorectal carcinoma. Chronic inflammatory bowel disease of long duration, typically over 10 years, is related to an increased risk for colorectal cancer development.
family members is increased even further when patients are diagnosed before the age of 60.14,15 Individuals with a first-degree relative with colorectal cancer have a twofold to fourfold increased risk for the development of colorectal carcinoma.16 In women, a personal history of ovarian, endometrial, or breast carcinoma is associated with an increased incidence of colorectal carcinoma. Chronic inflammatory bowel disease of long duration, typically over 10 years, is related to an increased risk for colorectal cancer development.
TABLE 1.3 Evolution of Colonic Polyps | |||||||||||||||||||||||||
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Various environmental factors have also been linked with the development of colorectal carcinoma including a diet high in fats or red meat and low in fiber. Inactivity and being significantly overweight have been linked to increased risk for development of colon cancer.17 Smoking and moderate-to-heavy alcohol use have also been found to enhance the risk for developing colorectal cancer.13
PREVENTION
Approximately 90% of all cases of colorectal cancer are preventable.1 To decrease the likelihood of developing colorectal carcinoma, the American Cancer Society recommends the consumption of healthy foods, particularly vegetables and fruits, maintaining a physically active lifestyle, and a healthy weight, as well as limiting alcohol intake.1 There have been multiple published studies evaluating the effect of different vitamins and medications in helping to prevent the development of colorectal carcinoma. Folic acid18,19 and calcium supplements20,21 have been found in some studies to reduce the occurrence of colorectal cancer. Although the exact mechanism is unclear, calcium is thought to bind to bile acids within the bowel lumen and thereby inhibit the carcinogenic effects of the bile acids.21 Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) have also been found to decrease the likelihood of developing colorectal adenomas and carcinoma.22, 23, 24, 25 and 26 They inhibit both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) which are enzymes involved in the synthesis of prostaglandin. COX-2 has been found to be elevated in up to 90% of sporadic colon carcinomas and 40% of colonic adenomas.25 A large randomized trial found that a low dose of 81 mg of aspirin daily had a moderate preventive effect on colonic adenomas after a few years of usage.22
In women, multiple studies have found a decreased risk for developing colorectal cancer with the use of hormone replacement therapy. A meta-analysis of epidemiologic studies of colorectal cancer found a 20% reduction in the development of colorectal cancer in postmenopausal women who had used hormone replacement therapy.27 In a randomized controlled trial evaluating healthy postmenopausal women, colorectal cancer rates were reduced by 37% in those who received hormone replacement therapy.28 However, the National Polyp Prevention Trial found no significant decrease in colorectal cancer recurrence in women with known colorectal adenomas taking hormone replacement therapy, although there was a significant risk reduction for recurrence of distal adenomas in users.29 Routine use of hormone replacement therapy in women is not recommended because of an associated increased risk of breast cancer, stroke, and pulmonary embolism.
CURRENT GUIDELINES
The best strategy for prevention of colorectal cancer is early screening. Screening allows the detection and removal of premalignant adenomatous polyps, thereby preventing progression of the adenoma-carcinoma sequence. It also allows for earlier diagnosis of colorectal cancer at a stage when the tumor is most curable. Screening leads to decreased morbidity and mortality from colorectal cancer.30 Current guidelines from the United States Preventive Services Task Force and the American Cancer Society recommend that screening for average-risk patients should begin at age 50.31,32
Colorectal cancer screening may be performed using several existing algorithms (see Table 1.4). The American Cancer Society recommends screening of average-risk adults aged 50 and older with one of the following options: (a) annual FOBT or fecal immunochemical testing (FIT), (b) flexible sigmoidoscopy every 5 years, (c) annual FOBT or FIT plus flexible sigmoidoscopy every 5 years (this combination is preferred over either test alone), (d) double-contrast barium enema (DCBE) every 5 years, or (e) conventional colonoscopy every 10 years.33 The digital rectal examination is not recommended as a screening tool for colorectal cancer, since <10% of cancers may be detected using this test.1,31 All of the currently suggested colorectal cancer screening tools offer specific benefits and limitations.
TABLE 1.4 American Cancer Society Recommendations for Colorectal Cancer Screening in Average-Risk Adults Beginning at Age 50 | ||||||||||||||||||
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