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Colorectal Cancer Screening Recommendations

Colorectal cancer is the second-leading cause of cancer death in the United States. Colorectal cancer is most frequently diagnosed among adults aged 65 to 74 years. The median age at death from colorectal cancer is 68 years. In their latest recommendation statement released on June 15, 2016, United States Preventive Services Task Force (USPSTF) found convincing evidence that screening for colorectal cancer accurately detects early-stage colorectal cancer and adenomatous polyps and reduces colorectal cancer mortality in adults aged 50 to 75 years. USPSTF believes that the benefit of early detection of and intervention for colorectal cancer declines after age 75 years. USPSTF does not recommend routine screening for colorectal cancer in adults 86 years and older.

The harms of screening for colorectal cancer in adults aged 50 to 75 years are small. The majority of harms are related to colonoscopy, either as a screening test or as follow-up for positive findings detected by other screening tests. USPSTF estimates there are 4 perforations and 8 major bleeding events per 10,000 colonoscopies. Colonoscopy risks increase with age.

Several options are available for colorectal cancer screening including fecal-based tests, endoscopic tests and imaging. USPSTF did not express a preference for one type of testing over another. Colonoscopy is by far the most commonly used method for colorectal cancer screening in the United States. However, no randomized clinical trial has been published showing that colonoscopy reduces colorectal cancer mortality. In contrast, multiple randomized clinical trials (RCTs) have shown that screening with guaiac-based fecal occult blood test (gFOBT) reduces colorectal cancer deaths.  

FOBT is based upon the principle that advanced adenomas and colorectal cancer are friable lesions that leak trace amounts of blood as a result of stool trauma and contractions of the colon. The overall specificity of guaiac FOBT has varied in the literature, ranging from 88% to 98%. Compared to colonoscopy, sensitivity is only 12% for advanced adenomas and 26% for colorectal cancer.

To improve sensitivity of FOBT, Beckman Coulter developed two newer versions, Hemoccult II and the Hemoccult II SENSA. Hemoccult II has a sensitivity of 25% to 38% and a specificity of 98% to 99% according to the US Preventive Services Task Force. Hemoccult SENSA has a sensitivity of 62% to 79% and a specificity of 87% to 96% for detecting colorectal cancer. Although this test has improved sensitivity over the previous versions, it has lower specificity and, therefore, more false-positive results.

Immunochemical FOBT (iFOBT) or fecal immunochemical test (FIT) were developed to specifically detect intact human hemoglobin. This test uses monoclonal antibodies directed against the globin moiety of human hemoglobin. These antibodies do not react with hemoglobin from nonhuman dietary sources. They also do not detect partly digested human hemoglobin from the respiratory or upper gastrointestinal tract. Thus, FIT is more specific than gFOBT.

Hemoccult ICT (Beckman Coulter) and OC FIT-CHEK by Polymedco are the two most popular brands of FIT available in the United States. According to USPSTF, OC FIT-CHEK has the highest sensitivity and specificity. Using a cutoff of 10 ?g hemoglobin per gram of feces, OC FIT CHEK had a sensitivity that ranged from 79% to 88% and specificity from 91% to 93%. Using the manufacturer’s recommended cutoff of of 20 ?g hemoglobin per gram of feces sensitivity ranged from 73% to 75% and specificity from 91% to 95%.

 Multitargeted stool DNA testing (FIT-DNA) is an emerging screening strategy that combines FIT with testing for altered DNA biomarkers in cells shed into the stool. Cologuard FIT-DNA test by Exact Sciences, is available in the United States. Sensitivity is 92% (95% CI, 84% to 97%) and specificity is 84% (95% CI, 84% to 85%). Its sensitivity to detect advanced adenomas and sessile serrated polyps measuring ?1 cm was 42% and its specificity to detect all nonadvanced findings was 87%. Screening with FIT-DNA is less specific than screening with FIT, resulting in more false-positive results and an increased probability of harm from follow-up colonoscopy.

FDA approved a blood test to detect circulating methylated SEPT9 DNA (Epi proColon; Epigenomics) in April 2016.  A single test characteristic study found the SEPT9 DNA test to have low sensitivity (48%) for detecting colorectal cancer.

References

http://www.uspreventiveservicestaskforce.org/Page/Document/RecommendationStatementFinal/colorectal-cancer-screening2#tab

Lin JS, Piper M, Perdue LA, et al. Screening for Colorectal Cancer: A Systematic Review for the U.S. Preventive Services Task Force. Evidence Synthesis No. 135. AHRQ Publication No. 14-05203-EF-1. Rockville, MD: Agency for Healthcare Research and Quality; 2016.

Imperiale TF, Ransohoff DF, Itzkowitz SH, , et al. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med. 2014;370(14):1287-97.

Premarket approval (PMA) for Epi proColon. US Food and Drug Adminstration. http://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfPMA/pma.cfm?id=P130001This link goes offsite. Click to read the external link disclaimer. Accessed April 21, 2016.

Centers for Disease Control and Prevention. Vital signs: colorectal cancer screening test use--United States, 2012. MMWR Morb Mortal Wkly Rep. 2013;62(44):881-8.

 

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