CRC Screening in the United States: To Detect or Prevent

By J. Ryan Cunningham, MD
Friday, December 14, 2018

Colorectal cancer (CRC) remains a major cause of morbidity and mortality in the U.S. with approximately 140,000 new cases diagnosed annually. This prevalent disease, affecting males and females equally, is the second leading cancer killer and causes nearly 50,000 deaths per year despite highly effective screening tests.

Over the past two decades, there has been an aggressive campaign spearheaded by the National Colorectal Cancer Roundtable (NCCRT) to increase the percentage of age-appropriate individuals screened for CRC. In 2014, the NCCRT announced a goal to achieve 80 percent of the population screened by 2018. At the outset of the 80 percent by 2018 campaign, approximately 60 percent of the population had undergone some type of CRC screening. If the NCCRT’s goal of having 80 percent of the appropriate individuals screened was accomplished, an estimated 277,000 CRC cases and 203,000 CRC deaths would be avoided by 2030.

Screening for CRC is based on detecting early-stage cancer, or better yet, preventing CRC altogether by identifying precancerous lesions in asymptomatic individuals and removing the lesions. Roughly 20 percent of females and 30 percent of males will develop precancerous polyps and the lifetime risk of being diagnosed with CRC is between 4–5 percent in the average-risk population.

The US Multi-Society Task Force (MSTF) on Colorectal Cancer, along with numerous other professional organizations, continues to recommend screening average-risk individuals (no personal or family history of CRC) beginning at age 50. African-Americans should start screenings at age45.

When counseling patients about the different screening tests available, it is imperative to understand the difference between tests designed to prevent CRC and those targeting the detection of CRC. Prevention tests include optical colonoscopy, CT colonography (also known as virtual colonoscopy), flexible sigmoidoscopy and pill-based capsule colonoscopy. CRC detection tests include stool-based fecal immunochemical testing (FIT), combination FIT-stool DNA (Cologuard; Exact Sciences; Boston), and the serum Septin9 assay (Epigenomics; Seattle). The Septin9 assay is not currently recommended by the MSTF and will not be further discussed.

Optical colonoscopy is the only MSTF Tier 1 prevention exam (Table 1) and remains the most widely used CRC screening tool in the US. Colonoscopy is preferred because it is the only screening test available that allows direct visualization of the entire colon, identification of precancerous polyps and removal of lesions in one exam. A single colonoscopy with polypectomy can reduce the incidence and mortality of CRC by more than 70 percent. Patients may voice concerns regarding the invasiveness of the exam, obligation to perform a laxative bowel cleanse and risks of sedation or anesthesia. Other recognized limitations include increased cost compared to other screening options, a lack of availability of high-quality endoscopists in rural areas and a very small risk of procedural complications, including perforation and bleeding. Because of this, physicians and other primary care providers should be prepared to discuss alternative screening options if their patients are hesitant or unwilling to proceed with colonoscopy.

Tier 2 prevention tests include CT colonography (CTC) and flexible sigmoidoscopy. CTC is performed in the radiology suite after an overnight bowel cleanse, does not involve procedural sedation and is recommended every five years for negative findings. This exam is limited in its ability to detect polyps of less than 6 mm or flat lesions of any size. CTC is associated with the risk of cumulative radiation exposure and can result in additional evaluation of incidental radiographic findings outside the colon. Patients must also be made aware of the limited ability to schedule same-day colonoscopy for positive CTC findings. When diagnostic colonoscopy has to be scheduled at a later date, repeat laxative bowel prep will be required as well.

Flexible sigmoidoscopy can be accomplished without an oral bowel cleanse. Enema preparation is performed immediately before the exam and most cases are completed without procedural sedation. Unfortunately, flexible sigmoidoscopy is limited by nonvisualization of the proximal colon where nearly 30 percent of all colon cancers develop. Increased sensitivity of CRC detection can be achieved by combining flexible sigmoidoscopy with annual FIT.

The only Tier 1 cancer detection test recommended by the MSTF is FIT. Noninvasive FIT has a one-time sensitivity for detecting CRC of 79percent, specificity of 96 percent and a low cost of approximately $20. No bowel prep is required and a single sample is sufficient, compared to guaiac-based fecal occult tests, which require up to three separate stool samples. The recommendation to repeat FIT annually can lead to screening fatigue and patients must be counseled on the necessity to follow through with diagnostic colonoscopy for a positive FIT.

The newest FDA approved stool-based cancer detection screening test is Cologuard. This test combines FIT with multitarget fecal DNA analysis of four molecular assays (KRAS, NDRG4, BMP3 and ß-actin) shed in the stool from cancerous or advanced precancerous lesions. Cologuard outperforms FIT with a one-time sensitivity for CRC of 92 percent, but is limited by a significantly lower specificity of 87 percent. It also carries a much larger price tag of $600 for privately insured patients and approximately $500 for Medicare patients. The false positive rate of 13 percent leads to a larger number of diagnostic colonoscopies compared to FIT, but available data suggests that asymptomatic patients with a positive Cologuard and negative complete colonoscopy do not require immediate repeat colonoscopy or additional evaluation of the remainder of the GItract.

The only Tier 3 exam recognized by the MSTF is capsule colonoscopy. The FDA approved this procedure for imaging the proximal colon in previously incomplete optical colonoscopies and more recently for patients who need colorectal imaging but are not candidates for colonoscopy or sedation. Bowel preparation is more extensive than colonoscopy, and the limited ability to perform colonoscopy on the same day as capsule ingestion for positive findings makes this option even less attractive for high-volume screening.

An additional consideration for counseling patients on the most appropriate screening test revolves around emergence of the serrated class of precancerous lesions in the colon. Serrated polyps are associated with approximately 30 percent of all CRCs. This class of lesions consists of hyperplastic polyps, sessile serrated polyps (SSPs or sessile serrated adenomas), and traditional serrated adenomas. Hyperplastic polyps are not currently considered precancerous, are most commonly found in the distal colon and do not require abridged screening intervals. Sessile serrated polyps are more commonly found in the proximal colon, typically flat lesions with few to no surface blood vessels and more difficult to detect on noninvasive screening exams (Cologuard outperforms FIT in detecting SSPs). Traditional serrated adenomas are the rarest of the serrated class. They are most commonly found in the left side of the colon and are frequently misinterpreted as conventional tubulovillous adenomas. Because SSPs are less likely to bleed, typically flat and commonly located in the proximal colon, colonoscopy gains its greatest advantage over all other screening exams in identifying these lesions.

At the end of the day, the best CRC screening test is the one that gets done. Using a tiered approach to screening recommendations focuses patient/provider discussions on fewer options and avoids overwhelming the patient with five or more tests to choose from. Colonoscopy has the highest sensitivity for CRC of all available screening options. It also affords the advantage of diagnosis and treatment in a single session with the longest interval between screening for negative exams. In fact, one or two negative high-quality colonoscopies may signal protection against CRC over the patient’s lifetime. Incorporating FIT as a viable alternative to colonoscopy establishes a foundation for screening that is straightforward and accommodates nearly every screening scenario.

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