Screening for Colorectal Cancer
In the United States, colorectal cancer (CRC) is the second most commonly diagnosed cancer in males and females. The age-adjusted incidence rate during the period 2006-2010 was 52.2 per 100,000 men and 39.3 per 100,000 women per year, according to data from the Surveillance, Epidemiology, and End Results (SEER) population-based cancer registries. The projected number of new cases in 2014 is 136,830, with 50,310 anticipated deaths, accounting for 8% of estimated new cancer cases and deaths in men and women.
CRC incidence rates established from the most recent data (2005-2009) decreased in males by 2.6% per year and in females by 2.1% per year. Mortality from CRC has also been steadily declining in the United States by 2.5% to 3% per year. These reductions have been largely attributed to increases in the use of CRC screening and removal of colorectal polyps.
Although an overall decline in CRC incidence and mortality has occurred, racial disparity is growing. African American males have the highest incidence (65.1 vs. 52.8 per 100,000) and stage-adjusted mortality (29.8 vs. 19.8 per 100,000) compared with white males. Racial differences in access to or utilization of CRC screening, a higher prevalence of comorbidities such as obesity, diabetes, and hyperlipidemia, and the early age at diagnosis in African Americans may explain some of the differences.
A variety of modalities may be used for CRC screening in the average-risk population. They include stool tests (fecal occult blood tests or stool DNA testing), radiologic tests (computed tomography [CT] colonography), and endoscopy (flexible sigmoidoscopy or colonoscopy). These tests have different rates of sensitivity, specificity, cost, potential harm, and adherence. Patients should have an opportunity to make an informed decision when choosing one of the screening modalities.
Multiple organizations have issued guidelines for CRC screening, most notably the American College of Gastroenterology (ACG), the U.S. Preventive Services Task Force (USPSTF), and the U.S. Multi-Society Task Force on Colorectal Cancer (USMSTF). However, adherence to guidelines remains a challenge, with significant overutilization of screening in average-risk persons and underutilization of surveillance in high-risk patients who are prone to CRC.
Who Should Be Screened? Determining Risk
The age to begin screening, the modality chosen for screening, and the interval between examinations depends on the presence or absence of known risk factors for CRC. Persons with no risk factors are considered to be at average risk of CRC with a cumulative lifetime risk of approximately 5% in both men and women. Patients at higher than average risk of CRC include patients with a personal or family history of CRC or polyps and patients with Crohn disease or ulcerative colitis. Patients with a genetic predisposition to CRC are at the highest lifetime risk of CRC. Hereditary CRC syndromes account for 5% of all CRC cases and warrant the most aggressive screening and surveillance.
The USMSTF, USPSTF, and ACG recommend that screening for CRC begin at age 50 years in average-risk, asymptomatic men and women. The ACG further suggests that African Americans start screening at age 45 years because of the increased incidence of CRC before age 50 years in this population.
Screening Average-Risk Persons
CRC screening tests can be divided into cancer prevention tests with the potential to identify both cancer and polyps and cancer detection tests that are primarily effective in diagnosing CRC ( Table 55-1 ).
|Cancer Prevention Tests||Cancer Detection Tests|
|Colonoscopy||High-sensitivity guaiac-based fecal occult blood test or fecal immunochemical testing|
|Computed tomography colonography (requires optical colonoscopy to achieve prevention)||Stool DNA|
Colonoscopy every 10 years is the preferred CRC prevention test, and annual fecal occult blood testing with high-sensitivity guaiac-based testing or the fecal immunochemical test (FIT) is the preferred cancer detection test. Table 55-2 summarizes the current screening guidelines for average-risk individuals issued by the ACG, USPSTF, and USMSTF.
|U.S. Multi-Society |
|U.S. Preventive Services Task Force||American College of Gastroenterology|
|Method||Interval for Screening|
|Fecal occult blood test||Annual||Annual||Annual|
|Flexible sigmoidoscopy||5 yr||5 yr||5 yr|
|Colonoscopy||10 yr||10 yr||10 yr|
|Computed tomography colonography||5 yr||Insufficient evidence to recommend||5 yr|
|Stool DNA||Unknown||Insufficient evidence to recommend||3 yr|
Cancer Prevention Tests
Colonoscopy is frequently cited as the gold standard CRC screening test because it has both diagnostic and therapeutic capabilities. Additionally, abnormalities detected on other CRC screening tests lead to a colonoscopy.
No randomized clinical trials of the effect of screening colonoscopy on CRC mortality have been performed, but epidemiologic and cohort studies have shown that exposure to colonoscopy is associated with up to a 75% decrease in CRC incidence, which includes a durable protective effect up to and greater than 10 years. This protective effect extends to patients who have no polyps detected on colonoscopy, in addition to those who have had a polyp removed. A recent follow-up on the National Polyp Study evaluating the long-term benefit of colonoscopy with polypectomy found a 53% reduction in CRC mortality when compared with the expected deaths from CRC in the general population. An inverse relationship between colonoscopy screening and death from CRC was found in a recent large Canadian population–based study. These investigators found that for every 1% increase in colonoscopy screening, a 3% decrease in CRC occurs.
The reduction in colorectal cancer mortality after colonoscopy varies by the site of the cancer, with less protection in the proximal than in the distal colon. In a Canadian case-control study that matched more than 10,000 patients who died with CRC to 5 control subjects each, colonoscopy was associated with lower mortality from left-sided colon cancer (adjusted odds ratio [OR], 0.33; 95% confidence interval [CI], 0.28 to 0.39) but not right-sided CRC (OR, 0.99; 95% CI, 0.86 to 1.14). It is suggested that the biologic differences between proximal and distal CRC (a higher proportion of CpG island methylation phenotype, DNA microsatellite instability, and BRAF mutations in proximal tumors and sessile serrated adenomas/polyps), the higher proportion of flat polyps in the proximal colon, and the technical skill of the endoscopist affect the miss rate of premalignant lesions and the development of interval CRC.
Quality indicators have been established to standardize colonoscopy and aid in determining areas for continuous quality improvement. The minimum quality standards include but are not limited to the cecal intubation rate (>90% for diagnostic cases and >95% for screening examinations), high quality of bowel preparation, colonoscopy withdrawal time (>6 minutes in screening examination), and adenoma detection rate (ADR; >25% in a mixed gender population aged ≥50 years or >30% for men and >20% for female patients older than 50 years). The ADR is defined as the proportion of screened subjects in whom at least one adenoma is detected. Endoscopists who meet these standards have decreased interval cancer rates. Compared with physicians who have an ADR greater than 20%, the hazard ratios for interval CRC based on ADRs of less than 11%, 11% to 14.9%, and 15% to 19.9%, were 10.94, 10.75, and 12.50, respectively ( P = .02 for all comparisons). In a recent study published, Corley and colleagues found a continued protection against CRC with an ADR above 32%. Each 1% increase in the ADR was associated with a 3 % decrease in the risk of CRC.
One major factor affecting the quality of mucosal inspection and subsequently ADR is the quality of bowel preparation. The American Society of Gastrointestinal Endoscopy/ACG Task Force recommends that the examination be considered adequate if it allows detection of polyps greater than 5 mm. Inadequate (poor or fair) bowel preparation is associated with an adenoma miss rate as high as 42% when a repeat colonoscopy is performed within 3 years of the initial suboptimal examination. The quality of bowel preparation worsens with a longer time interval between completion of the preparation and the start of colonoscopy. A meta-analysis of nine studies concluded that receiving at least half of the bowel preparation on the day of the examination, also known as “split-dose” bowel preparation, resulted in more excellent and good results (OR, 3.46; 95% CI, 2.45 to 4.89) compared with night-before dosing. Therefore, to maximize bowel preparation quality, it is recommended that the colonoscopy be started within 3 to 5 hours of the last dose of preparation.
Three of four randomized controlled trials have shown that flexible sigmoidoscopy decreases CRC incidence up to 25%. Two of the three trials found up to a 30% reduction in mortality from CRC.
Flexible sigmoidoscopy is often performed without sedation and does not usually require an oral bowel preparation, which is one barrier to colonoscopy. However, the examination is limited to the left colon, and about 37% of lesions are beyond the reach of the flexible sigmoidoscope. Patients for whom precancerous lesions are detected with sigmoidoscopy should be referred for a colonoscopy.
Computed Tomographic Colonography
Also known as virtual colonoscopy, CT colonography (CTC), a promising CRC screening modality, does not require sedation and has very low immediate test-related complications. However, CTC currently is not covered by Medicare or by many commercial payers, it requires an extensive bowel preparation, and it has poor discrimination for colorectal lesions less than 6 mm, flat lesions, and serrated lesions. A meta-analysis by Mulhall and colleagues showed that the sensitivity of CTC improved as the polyp size increased, with a sensitivity ranging from 48% for polyps less than 6 mm to 85% to 93% for polyps larger than 9 mm. Similar findings were reported in a more recent randomized controlled trial. The American College of Radiology Imaging Network National CT Colonography Trial assessed the accuracy of CTC for detecting histologically confirmed colorectal neoplasms (adenomas and cancers), using colonoscopy as the reference standard. Although CTC had a sensitivity of 90% for the detection of large lesions, its sensitivity for the detection of adenoma or cancers was 65% for lesions larger than 5 mm, 78% for lesions 6 mm or larger, and 84% for lesions 7 mm or larger.
Nonrandomized controlled studies show that the detection rate for advanced neoplasia was similar between screening patients undergoing CTC (3.2%) or colonoscopy (3.4%), with a 7.9% referral rate for follow-up colonoscopy after CTC. The Special Interest Group in Gastrointestinal and Abdominal Radiology (SIGGAR) study, a recent large randomized study of symptomatic patients, showed that the yield for colorectal cancer or large polyps was identical with CTC and colonoscopy with a very low miss rate (1 of 29 in the CTC group). However, the referral rate for colonoscopy after CTC was unexpectedly high (30%), a fact that has major cost implications.
Adherence to CTC has been shown to be higher than adherence to colonoscopy in some studies. In one analysis, significantly more patients accepted the invitation to have a CTC than to undergo colonoscopy (34% vs. 22%).
Radiation exposure and radiation-related cancer risk should be considered, especially with repeated scanning. Other limitations of CTC include the need for a standardized technique, a consensus in reporting the findings, and the dilemma posed by the number of incidental extracolonic findings identified on imaging, which are present in up to 16% of patients.
The USMSTF recommends that CTC screening begin at age 50 years; however, the interval for repeat examination after a negative CTC is uncertain. The authors state that it is “reasonable to repeat exams every 5 years if the initial CTC is negative for significant polyps until further studies are completed and are able to provide additional guidance.” The USMSTF guidelines recommend surveillance colonoscopy as opposed to CTC for patients with polyps 6 mm or larger detected with CTC.