Abstract
Corresponding Author(s)
Mark K. Kauffman, DO, MS Med Ed, Physician Assistant Program, Department of Family Medicine, Lake Erie College of Osteopathic Medicine, Gannon University, 1858 W Grandview Blvd., Erie, PA 16509.
E-mail address: mkauffman@lecom.edu.
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Colorectal cancer (CRC) is the third most common ma- lignant neoplasm worldwide and the second leading cause of cancer deaths in the United States, with only lung cancer being more prevalent.1-3 It is estimated that there will have been 150,000 new cases diagnosed in the United States in 2010 and more than 50,000 deaths as a result of this dis- ease.4,5 The incidence of CRC has been declining since the 1990s owing to increased physician and patient awareness, better compliance with screening guidelines, and earlier and more effective treatment of precancerous colorectal lesions; however, screening rates remain low.2
The incidence is higher in men than in women (Fig. 1).6 The age-adjusted mortality rates for men and women are 24.8 per 100,000 per year in men and 17.4 per 100,000 per year in women.6 Approximately 6% of Americans are ex- pected to develop CRC within their lifetime and about half of those will die from it. Age-specific incidence and mor- tality rates show that the vast majority of cases are diag- nosed after age 50, with only approximately 7% of CRC occurring in those younger than age 50 years.6
Screening is an effective way to reduce CRC mortality, both by removing premalignant lesions and detecting early cancers. The US Preventative Task Force recommends screening beginning at age 50 years and continuing until age 75 years.7
Factors affecting screening
Evidence suggests that CRC screening is simultaneously underused in patients who would derive benefit from screening, overused in patients with advanced age or co- morbidities who would not derive benefit, and misused when abnormal results are not appropriately followed-up or inadequate testing is performed.2,8
Although there has been an increase in CRC screening rates from 30% in 1997 to 55% in 2008, it remains much lower than the 80% screening rates for breast cancer.2,5 Among Americans age 50 and older, 18% had a fecal occult blood testing (FOBT) during the preceding year and approx- imately 50% had a sigmoidoscopy or colonoscopy during the previous 10 years.7 This suggests a need for continued improvement in depth and frequency of patient/provider discussions about CRC screening to improve screening rates.
Those with the lowest screening prevalence include per- sons aged 50 to 59 years, Hispanics, persons with lower income, those with less than a high school education, and those without health insurance.3,9 Lack of a primary care provider or adequate health insurance and limited income contribute to the underuse of CRC screening. This may be compounded by the rising use of colonoscopy, the most expensive screening test, as the preferred method of screen- ing.10
In 2001, Medicare approved payment for screening colonoscopy for those of average risk as defined by national guidelines as individuals without a personal or family his- tory of CRC or adenomatous polyps.10 Medicare does not pay for screening by computed tomography (virtual) colonoscopy (CTC).11 Private insurance coverage is vari- able in the United States, resulting in patients with high deductible health plans being screened more often with FOBT testing than with colonoscopy.12
Emmons examined the impact of health insurance on racial/ethnic disparities in CRC screening. A low-income, racial/ethnic minority sample in which 97% had health insurance that covered CRC screening, identified a self- reported 67% screening rate with a 52% adjusted rate based on a validation substudy.13 This rate was higher than among
similar population-based samples that had lower levels of insurance coverage.13 No screening rate differences based on race/ethnicity were identified. This study suggests that insurance coverage for CRC screening should be considered as part of a comprehensive approach to address CRC dis- parities.13
Multiple studies have shown that low rates of cancer screening are associated with socioeconomic status, ethnic origin, age, and gender. Psychological factors such as em- barrassment, fear of cancer, and lack of knowledge may also affect cancer screening rates. More than 44 studies exam- ining factors affecting compliance with CRC screening guidelines found that a positive attitude toward screening was the primary factor in compliance with screening.14
For many women, gynecologists are an important source of primary care. Thirty-seven to 93% of obstetricians/gyne- cologists consider themselves to be primary care provid- ers.15 In a study of gynecologic patients, it was found that having multiple providers recommend colorectal screening improved a patient’s intention to undergo CRC screening. Compliance, however, was primarily driven by primary care provider recommendations.15 Strategies should be in place to prompt gynecologists to discuss CRC screening in eligi- ble patients as part of the annual maintenance examination, which may help to improve screening compliance in female patients.
A recent study published in the British Journal of Cancer found that men, older individuals, and those with South- Asian ethnic backgrounds were more likely to have a neg- ative attitude toward CRC screening. Persons of Caribbean ethnic background and patients experiencing abdominal pain, bleeding, fatigue, or multiple symptoms were more likely to have a positive attitude toward screening.14 Devel- opment of culturally relative screening strategies and in- creasing patient educational materials outlining the symp- toms and signs of CRC may increase adherence in targeted screening populations.
Pathogenesis
More than 95% of CRCs are adenocarcinomas that arise from adenomatous polyps.16 The progression from adenoma to carcinoma is slow and it is believed that the removal of adenomatous polyps is responsible for the decline in CRC in the United States.17 Some CRCs arise from nonpolypoid adenomas that are flat or depressed and account for 22 to 36% of identified adenomas.18 Flat and depressed lesions can be difficult to detect and may be more likely to contain dysplastic changes or cancer than polypoid ones of compa- rable size.18
The risk of developing CRC increases with adenoma size, number, and histology, with villous adenomas having a greater risk than tubular adenomas.19 The finding of a single adenomatous polyp suggests a propensity to form polyps, and the patient should be evaluated for other lesions in the colon and rectum.
Risk factors for colorectal cancer Patients are categorized as either “average risk” or “in- creased risk.” Average-risk individuals are defined as those without a personal or family history of CRC or adenoma- tous polyps and account for the majority of the population. Most cases of CRC occur in average-risk individuals.9 In- creasing age, male sex, black race, and history of smoking are associated with an identified increase in incidence of CRC but are not used in the classification of average-risk versus increased-risk categories.9
Patients are considered to be at increased-risk under the following conditions: (1) A first-degree relative with colon cancer or advanced adenoma (>1 cm, or high-grade dys- plasia or villous elements) diagnosed at age <60 years; (2) two first-degree relatives diagnosed at any age; or (3) per- sonal history of CRC, polyp, inflammatory bowel disease including ulcerative colitis or Crohn’s Disease; Lynch syn- drome/hereditary nonpolyposis colon cancer (HNPCC); or familial adenomatous polyposis (FAP)20 (Table 11,17).
Family history
In the United States, 5% of adults aged 20 to 79 years report a first- or second-degree relative with a history of CRC.21 The incidence is believed to be because families share behaviors and environmental exposures along with their genes. When screening for genetic risks for CRC, the review of family history should include inquiry of blood relatives diagnosed with CRC or polyps (Fig. 222-24). If positive, distinction of first-degree relatives (parent, sibling, or child) versus other relatives (grandparent, cousin, niece, or nephew) should be made for each family member identified along with the age at diagnosis.22Individuals with a sibling who has had CRC diagnosed before the age of 60 are at increased risk for CRC and may derive benefits from screening.
Family history is commonly overlooked. In a survey of patients aged 35 to 55 years enrolled in a group practice, 39% of patients reported that they had not been asked about family history.20 In patients with a strong family history of CRC, 46% of patients did not know they should be screened at an earlier age and 55% had not been appropriately screened.20
Reviewing the family history for CRC or polyps should be part of routine health maintenance and occur at least on a yearly basis because cancers may arise in family members as they age. A positive family history of CRC prompts screening to begin 10 years before the earliest age of diag- nosis in a relative.20 For example, during a routine history and physical examination, your 34-year-old male patient’s family history reveals a brother diagnosed with CRC at 45 years of age. This would prompt CRC screening in your patient to begin at 35 years of age instead of 50 for average- risk patients.
Table 1 Risk factors for colorectal cancer
Personal history of colorectal polyps or colorectal cancer Personal history of inflammatory bowel disease
Family history of colorectal cancer Inherited syndromes including:
Familial adenomatous polyposis (FAP)
Lynch syndrome/Hereditary nonpolyposis colon cancer (HNPCC)
Turcot syndrome
Peutz-Jeghers syndrome African American Race
Jews of Eastern European descent (Ashkenazi Jews) Lifestyle-related factors including:
Diet high in red meats (beef, pork, lamb)
Diet high in processed meats (hot dogs and some luncheon meats)
Physical inactivity Obesity
Smoking
Heavy alcohol use Type 2 diabetes
Screening for a family history of CRC has been found to be cost-effective and has been estimated to save $58,228 per year of life gained.25 The highest risk is seen in people with multiple first-degree relatives or relatives who have devel- oped CRC before the age of 50 years and is greater for relatives of patients with colon, compared with rectal, can- cer.26 People with a family history of CRC are screened at an earlier age than people at average risk because cancer will occur earlier in their life, not uncommonly in the 30s or 40s.26 If a patient has a family history of Lynch syndrome or FAP, aggressive screening consisting of an annual colonoscopy beginning at age 20 to 25, or 10 years before the earliest age of colon cancer diagnosis in the family (whichever comes first) and/or genetic testing should be pursued.27-29
Colorectal cancers occurring in distant relatives or a single first-degree relative after the age of 60 are associated with a small increased risk of developing CRC, which is not large enough to change clinical advice or screening prac- tices from those recommended for the general population.30 Patients who have a family member with an adenomatous colonic polyp may also be at increased risk for CRC but it is uncertain whether an earlier onset of screening is indi- cated in patients whose possible increased risk relates only to a family history of polyps.30
Colorectal cancer screening guidelines
CRC screening recommendations must be first approached by appropriate classification of patients as average-risk or increased-risk (Fig. 2).22-24
Figure 2 Colorectal cancer screening algorithm.
Screening for average-risk patients
Table 2 Colorectal cancer screening test options and frequency of evaluation
Tests that primarily Tests that find polyps and cancer find cancer (preferred)
Fecal occult blood test Colonoscopy/every 10 years (gFOBT)/yearly
Fecal immunochemical test (FIT)/yearly
Stool DNA test (sDNA)/interval uncertain
Flexible sigmoidoscopy/every 5 years
Double-contrast barium enema (DCBE)/every 5 years
CT colonography (CTC)/every 5 years
For average-risk individuals, both men and women should begin screening for CRC at age 50. Frequency of testing is based on the method of screening used. Testing options are divided into two categories: tests that primarily find cancer and those that find polyps and cancer (Table 2).31-33 The tests that are designed to find both early cancer and polyps are preferred if these tests are available and the patient is willing to have one of these more invasive tests. Multiple guidelines for CRC screening have been pub- lished. The United States Preventive Services Task Force (USPSTF) recommends three screening options for adults ages 50 to 75 years, which have been found to be roughly equivalent in screening for CRC31 (Table 331-33). These guidelines did not weigh the value of identifying premalig- nant lesions (prevention) over the detection of cancer (screening). The National Comprehensive Cancer Network (NCCN) issued revised guidelines in January 2010 that recommend colonoscopy every ten years when available, as
the preferred screening method beginning at age 5032 (Table 331-33). The NCCN did not come to consensus regarding CTC or fecal DNA as screening modalities. The American College of Gastroenterology (ACG) 2008 guidelines recom- mend colonoscopy as the preferred screening/prevention test (Table 331-33). The ACG recommends initiating screen- ing at age 45, rather than 50, for African Americans.33
Table 3 Colorectal cancer screening guideline comparison
United States Preventive Services Task Force Options 2008
Colonoscopy every 10 years
Flexible sigmoidoscopy every 5 years, with sensitive FOBT every 3 years Annual fecal occult blood test (FOBT)
with a sensitive test
National Comprehensive Cancer Network (NCCN), 2010
Colonoscopy every 10 years (preferred)
Sigmoidoscopy every 5 years with or without annual stool testing
Annual stool testing with guaiac or immunochemical reagent
Barium enema is only recommended when a colonoscopy cannot be performed
American College of Gastroenterology (ACG) 2008
Colonoscopy (preferred)
Fecal immunochemical test preferred for patients who decline colonoscopy
Screening for increased-risk patients
The ACG recommends the following guidelines for screening patients at increased risk for CRC because of a family history33:
Screen with colonoscopy
If a single first-degree relative was diagnosed at age 60 years or older with CRC or an advanced adenoma (>1 cm, or high-grade dysplasia or villous elements), screen- ing with colonoscopy is recommended every 10 years beginning at age 50
If a single first-degree relative was diagnosed before 60 years with CRC or an advanced adenoma, or two or more first-degree relatives had CRC or advanced adenomas at any age, screening with colonoscopy is recommended at age 40 or 10 years before the youngest relative’s diagno- sis, and should be repeated every five years.
Screening in the elderly
The decision whether to recommend screening for a patient over 70 years of age should depend on the patient’s health status, anticipated life expectancy, risk for CRC, and personal values.34,35 The following factors should be con- sidered in this decision:
Patients with a life expectancy less than five years would not be expected to benefit from colorectal screening.
The risks associated with the performance of a colonos- copy increase with age and comorbidities, including car- diopulmonary disease, diabetes mellitus, and history of stroke.36 If the patient is expected to live long enough to benefit from screening, CTC should be considered.
Sigmoidoscopy has reduced sensitivity in the elderly be- cause advanced neoplasias tend to occur more proximally as patients age.
Most guidelines recommend that screening for CRC stop if the patient’s life expectancy is less than 10 years.16,31 The USPSTF guidelines recommend that patients over age 85 not be screened, and recommends against screening in adults 76 to 85 years, unless there are individual consider- ations that favor screening.31 Overuse of screening in this population of advanced age and comorbidities and limited benefit remains a concern.
Screening modalities
There are advantages and disadvantages to each of the tests used in CRC screening (Table 4).2,22,31 Screening with FOBT, flexible sigmoidoscopy, or colonoscopy reduces CRC mortality in adults age 50 to 75 years.7,31 Follow-up of positive FOBT, sigmoidoscopy, or CTC requires colonos- copy. Misuse occurs when abnormal results are not appro- priately followed up or inadequate testing is performed, such as FOBT performed only on a stool sample taken during digital rectal examination at an office visit. The multiple stool take-home test should be used. A single sample performed at the office is not adequate for testing.2 The benefit of less invasive screening tests is that they may reduce the number of colonoscopies required and their related risks. The benefits of detection decrease once a patient reaches 75 years of age. Competing causes of mor- tality make it less likely that the benefit of early detection will be realized with advancing age.31
Patient preferences have also been evaluated. One of the largest studies to evaluate procedure preferences in detail involved 614 increased-risk patients who underwent colonoscopy, CTC, and double-contrast barium enema (DCBE).37 Patients preferred colonoscopy to the former two procedures and were least satisfied with DCBE.
Increasing colorectal screening rates
Current CRC screening rates range from 45 to 60% in the United States, which is lower than the 80% screening rates for breast cancer.2 If everyone aged 50 years or older had regular screening tests, 60% or more of deaths from CRC could be avoided.38 To continue to increase CRC screening, financial barriers will need to be eliminated and appropriate follow-up adhered to. Health reform is anticipated to reduce the financial barriers to CRC screening, but multiple factors influence screening.
Table 4 Advantages and disadvantages of colorectal cancer screening tests
Test Advantages Disadvantages
Fecal occult blood test (FOBT)
No bowel preparation is necessary Samples can be collected at home Low cost
No risk of colon perforation/bleeding Minimal discomfort
Low detection rate for polyps False-positive results are possible.
Dietary restrictions include avoiding: red meat, certain vegetables, vitamin C, iron supplements, and aspirin. (These restrictions and changes are not required for immunochemical FOBT.)
Colonoscopy may be necessary if the test is positive
Sigmoidoscopy Minimal discomfort
Biopsy and removal of polyps during the test may be possible
Less bowel preparation than for a colonoscopy
Colonoscopy The entire colon and the rectum can be
visualized
Diagnostic and therapeutic Highly accurate
Biopsy and removal of polyps can be performed
Covered by most insurance plans Cost-effective
Virtual colonoscopy The entire colon and the rectum can be
visualized Therapeutic only Highly accurate
Risk of bleeding or tearing/perforation of the colon is very rare
No sedation needed
May detect clinically important extracolonic pathology
Cost-effective in some analyses
Only the rectum and the lower part of the colon can be viewed
Serious complications* are estimated to be 3.4 per 10,000 procedures
Colonoscopy may be necessary if the test is positive
Not all polyps (up to 27% are missed), nonpolypoid lesions, and cancers are detected
Bowel preparation is necessary Sedation is required
Perforation is estimated to occur in 3.8 per 10,000 procedures Serious complications* are estimated to occur in 25 per
10,000 procedures Absence from work
Poor patient acceptance in some instances Up to 50% of polyps <5 mm are missed Bowel preparation is necessary
Detection of a polyp or nonpolypoid lesion 6-9 mm or larger requires optical colonoscopy to remove the polyp or lesion or perform a biopsy
Extracolonic findings are found in 7% to 16% of cases requiring further testing, adding expense and morbidity
Radiation exposure
Limited insurance coverage (not covered by Medicare or Medicaid)
Double-contrast barium enema (DCBE)
Digital rectal examination (DRE)
The entire colon and rectum can be visualized
Therapeutic only Complications are rare No sedation needed
Part of physical examination after age 50 No bowel prep required
Test is quick and painless
Small polyps and cancers may be missed Bowel preparation is necessary
Optical colonoscopy is required to remove polyps or perform a biopsy
False positives are possible
Detection of abnormalities in the lower part of the rectum A colonoscopy may be necessary if the test is positive
*Serious complications include death, perforation, major bleeding, severe abdominal pain, cardiovascular events, or an event requiring hospitalization.
Interventions that have proven effective at increasing CRC screening—including electronic medical records with patient reminder systems, one-on-one education, decision aids, referrals by providers and organization of office staff to support a program of patient education, monitoring, out- reach, and follow-up—should be implemented along with systems to ensure appropriate compliance and follow-up of positive results of CRC screening.5,39
In a recent randomized, controlled trial conducted at Kaiser Permanente Northwest, it was found that automated telephone calls increased completion of FOBT over the traditional approach of mailing reminders.40 Public education should be continued to help the public understand the benefits of colorectal screening.3
Risk factor modification
Patients should be encouraged to stop smoking and increase their intake of dietary fiber and increase their physical activity. Although there is some evidence that postmeno- pausal hormone therapy, aspirin, or nonsteroidal antiinflam- matory drugs can decrease the risk for CRC, the risks of long-term use of these drugs outweigh the benefits, even for persons with a family history of CRC.41
Conclusion
CRC is the second leading cause of death among North Americans of both sexes.1-3 Screening rates for CRC have increased over the past decade but remain below appropriate levels.2,5 Improvement must be made through physician and patient education, patient reminders, and the use of elec- tronic medical records. Providers should incorporate family history for CRC such as through a screening algorithm (Fig. 2) more frequently in patient encounters, and they should be able to correctly categorize patients as average-risk or in- creased-risk to provide screening options that include risks and required frequency of testing. Screening for average- risk individuals should begin at age 50 and continue until age 75. African-American men should begin CRC screening at age 45. Individuals at increased risk should begin screen- ing at age 40 or 10 years before the earliest age of diagnosis in a family member. Colonoscopy has been recognized as the preferred method for CRC screening in the United States, and with regular screening, more than 60% of deaths from CRC can be prevented.
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