Colorectal Cancer (CRC) is the third most common cancer in the United States. The majority of CRCs arise from adenomatous polyps, and therefore the removal of these polyps before they become cancerous can prevent the manifestation of CRC. The goal of CRC screening is to detect these precancerous and cancerous lesions at an early stage because early diagnosis results in improved overall prognosis.
Various CRC screening programs have been adopted in the major pharmaceutical markets. The U.S. Preventative Services Task Force (USPSTF) recommends CRC screening should be carried out in men and women between the ages of 50 and 75. The presence of widespread CRC screening in the United States since the 1980s and 1990s as well as the development of more accurate screening technologies led to a decrease in CRC incidence in the 2000s because screening is able to detect nonmalignant lesions that can be removed before they develop into an invasive carcinoma. However, while screening can reduce CRC incidence, overall the effects of the aging population in all major pharmaceutical markets counterbalance this reduction because the risk of CRC increases exponentially with age. Apart from the effect on incidence, CRC screening has led to a shift in the stage distribution at diagnosis; specifically CRC screening has led to a decrease in the proportion of CRC patients diagnosed at advanced stages. From the pharmaceutical industry perspective, because of the strong association between risk of disease recurrence and stage at diagnosis, this shift in stage distribution will limit the growth in the number of drug-treatment opportunities in the advanced disease setting.
The most thorough method of screening is a colonoscopy. This involves using a camera to look at the entire length of colon and rectum, and usually takes around 30 minutes. Any polyps can also be removed during the colonoscopy session. However, the patient must not eat the evening before the test, and the bowel must be cleaned with strong laxatives. Patients are also sedated during the test. There is also a very small risk of bowel perforation during the colonoscopy. Colonoscopies should only need to be carried out in healthy individuals once every 10 years.
A slightly less intrusive method of screening is a flexible sigmoidoscopy. This requires less bowel preparation, and the patient is not sedated during the procedure. However, this test only looks at the lower half of the colon tract, which is the area which is most frequented by polyps, and only some polyps can be removed concurrently. It is recommended that sigmoidoscopies are carried out every five years, however if any adenomatous polyps are detected this is generally followed up with a colonoscopy.
The FDA has recently approved the use of Given Imaging's PillCam Colon, which is a camera inside a pill-sized capsule, for patients who are considered unsuitable for traditional colonoscopies. Whilst some bowel preparation is still needed, it is a much less invasive procedure than colonoscopy and sigmoidoscopy. The video data is automatically stored on a data recorder worn on the patient's waist, and the capsule does not need to be retrieved afterwards. It is however not considered to be a general replacement for colonoscopy, and that if there are any suspicious lesions detected a follow-up colonoscopy will be required.
A non-invasive method for colorectal screening involves testing stools for the presence of blood, as adenomatous polyps typically contain damaged blood vessels, which release blood into the feces. The presence of blood in the stool however may not necessarily be caused by adenomatous polyps. There are many different tests available, but the most common is the fecal immunochemical test (FIT). This test does not require any dietary restrictions; samples can be taken at home and can be posted directed to the laboratory. The sensitivity (ability to detect adenomas) and specificity (the ability to detect patients who do not have adenomas) varies dramatically depending on the type of FIT test used, but a recent study has shown FIT test sensitivity for CRC between 80-100%, sensitivity for advanced neoplasia between 28-42%, with specificity for both at around 95% (Hernandez V, et al.). These tests should be carried out every year, or every five years in combination with a sigmoidoscopy. Any positive tests must be followed up with a colonoscopy.
There are two lab-based CRC screening tests which have FDA hearings this month. Exact Biosciences? Cologuard, a DNA-based stool test, showed sensitivity for CRC at 92%, sensitivity for advanced adenomas at 42%, with an overall specificity of 87%. Although it was noted by Exact Biosciences that Cologuard was superior to FIT for advanced adenomas, this improvement is likely to be quite modest when considering historical FIT data. Due to the likely premium price of Cologuard (around $400, compared to FIT testing of between $25-$100), uptake is likely to be quite low, even if it does gain FDA approval. Epigenomics? Epi proColon test detects methylation of the SEPT9 gene in cell-free DNA, which is present in the blood plasma of colorectal cancer patients. Epi proColon shows slightly inferior results to FIT and Cologuard (sensitivity of 70% for CRC and less than 20% for advanced adenomas, at a specificity ranging from 84-91%), but has the advantage of being a blood-based test rather than a stool-based test. The Epi proColon test has been approved in Europe since 2009.
To conclude, there are many methods used to screen for colorectal cancer, most of which were not included in this post, with colonoscopy being the preferred method by oncologists. However any screening for colorectal cancer is better than no screening because early detection can potentially save your life.