Blood Test for Colorectal Cancer Screening

As many of you are likely aware, colorectal cancer (CRC) is a major cause of cancer-related death worldwide. According to the NIH, it is the fourth most commonly diagnosed cancer and third cause of cancer death globally. Incidence of CRC cancer increases with age due to accumulation of genetic mutations over long periods of time. Therefore, those at particularly high risk include individuals over the age of 50. Unfortunately, diagnosis of CRC often occurs in late-stage disease, when survival outlook is grim and treatment options are minimal. 

However, on a more positive note, CRC is a highly preventable cancer. As discussed in our previous article on Aspirin for Colorectal Cancer prevention, lifestyle factors, such as obesity, consumption of excess red meats, increased sedentary time, sleep deprivation, smoking, and alcohol can play a major role in either disease progression or prevention. In addition, the recent proliferation of CRC screening has made early disease detection possible. As a result, mortality associated with colorectal cancer has decreased, despite its recent spike in incidence.

Impact of Colorectal Cancer Screening and Guidelines

Colorectal cancer screening has made an extensive positive impact on CRC mortality rates in recent years. According to a 2020 systematic review and meta-analysis, implementation of colonoscopic screening has led to a 62% relative risk reduction in CRC mortality. In addition to colonoscopy, newer screening modalities such as fecal immunochemistry, the guaiac fecal occult blood test, and flexible sigmoidoscopy have also been found to significantly reduce CRC mortality rates. However, 10-yearly colonoscopy currently remains the single most effective screening method for colorectal cancer. 

As a result of this mounting favorable evidence, the US Preventive Services Task Force recommends that all adults age 50-75 receive some method of CRC screening. How often screening is done depends on the modality. Colonoscopy is recommended every 10 years for adults in this age range. Flexible sigmoidoscopy should be done every 5 years. Fecal immunochemistry and guaiac-based fecal occult blood testing should be done annually or every 3 years. 

Adherence to Screening and Barriers

Despite the recent advancements in CRC screening and their positive effects, there is still room for improvement and further CRC mortality reduction with increased adherence to screening protocols. The American Cancer Society has found that over ⅓ of adults age 45 and above are not screened for colorectal cancer as recommended. This leaves immense potential for further mortality reduction. The current goal by the CDC is increasing the screening prevalence to 80% by the year 2030. If successfully accomplished, this could reduce CRC-related deaths in the US by another 33%. 

Barriers to CRC screening adherence are numerous. However, the top reported reasons for foregoing colorectal cancer screening include patient discomfort with colonoscopy procedures and cost. Unfortunately, these barriers are inherent to the procedures of colonoscopy and stool tests and can therefore be difficult to overcome with the current testing methods. 

A New cfDNA Blood Test

A brand-new CRC screening method called cfDNA testing may be the key to increasing colorectal screening adherence. A March 2024 New England Journal of Medicine publication by Chung et al. provides promising preliminary results for this simple blood test in detecting CRC and advanced neoplasia, a category that includes both cancer and precancerous lesions. 

In this study, approximately 8,000 patients from 265 primary care and endoscopy sites at average CRC risk had a blood draw done prior to their CRC screening session. The blood specimens were then analyzed for cell free DNA (cfDNA), which is free DNA in the bloodstream located outside of cells. Cell free DNA can provide insight about the presence of malignancy because cancer causes increased cell turnover, meaning cfDNA levels will be increased in cancer patients. Furthermore, cfDNA analysis can reveal genetic mutations associated with specific cancers, which is helpful in determining their cause and tailoring therapy.

Results of the Chung et al. study indicate that a cfDNA based blood test has a sensitivity, or true positive rate, for colorectal cancer of 83%. The specificity, or true negative rate, for advanced neoplasia, which includes both precancerous lesions and CRC, was found to be 90%. Both of these values are considered acceptable for use of the new screening test. According to William Grady, MD, a gastroenterologist, the cfDNA blood test “has an accuracy rate for colon cancer detection similar to stool tests used for early detection of cancer” and “could offer an alternative for patients who may otherwise decline current screening options.” This could be a huge step forward in increasing CRC screening adherence by directly addressing the barrier of patient discomfort. 

Conclusion

Colorectal cancer remains one of the top causes of cancer-related mortality worldwide, likely because it is often diagnosed in its later stages. However, recent development and implementation of CRC screening methods has helped decrease its mortality, despite spikes in overall disease incidence. Now, the major area of focus is increasing screening adherence among patients, which could further drive mortality rates down. A newly developed blood test that analyzes extracellular DNA can help achieve this goal by addressing the major barrier to screening, patient discomfort. All in all, cfDNA blood testing has comparable sensitivity for CRC and specificity for advanced neoplasia with stool-based testing methods currently in use. The world of gastroenterology looks forward to its likely future release and potential to save patient lives. 

Summary

Colorectal cancer screening protocols have caused incredible strides in decreasing mortality associated with CRC, the third leading cause of global cancer deaths. However, there is still room for improvement in CRC screening impact by increasing patient adherence. Major barriers to CRC screening include patient discomfort with procedures and cost, both of which can be addressed through the recently developed cfDNA blood test. This new screening protocol involves analysis of extracellular DNA through a simple blood draw. It has a sensitivity for CRC of 83%, along with a specificity for advanced neoplasia of 90%, both of which are comparable to stool-based testing methods and are therefore acceptable values for its clinical use. Implementation of this new screening method could help achieve the CDC goal of increasing CRC screening adherence to 80% by 2030, which could bring about a 33% further decrease in mortality rates.