Colorectal cancer is the second leading cause of cancer-related death in the United States. Accurate and early detection of CRC and precancerous lesions is critical for reducing incidence and preventing deaths from this disease.
Through the tremendous creativity and tireless efforts of many, substantial progress has been made over recent years. Advances in the awareness, adoption, and performance of average-risk screening have also contributed meaningfully to reducing the CRC burden over the last 20 years.
But there is more to do. Today, nearly one in three adults ages 45-74 is not up to date with current guideline recommendations for CRC screening.
To close this gap, continued advancement and acceleration of screening test innovation is needed to address the unmet needs of patients who have not yet found an acceptable option among the established, existing strategies.
To make a real impact on cancer outcomes, a patient-centric approach is needed, one that includes new screening innovations that improve our ability to accurately detect not just early-stage cancers but also advanced precancers while also being acceptable, accessible and easy for patients to use.
The introduction of Cologuard, the first non-invasive multi-target stool DNA (mt-sDNA) test, a decade ago, illustrates what this approach to screening innovation can achieve.
The Cologuard test transformed CRC screening access, reaching more average-risk adults of screening age than screening colonoscopy and other available tests could do alone.
According to the Centers for Disease Control and Prevention, use of the Cologuard test was the primary contributor to the increase in colon cancer screening rates in adults ages 50 to 75 from 63% in 2015 to 72% in 2021.
In the last 10 years, more than 17 million screenings were completed with the Cologuard test. More importantly, modeling studies suggest that 80% of the cancers detected by the Cologuard test in that time were early stage, including 42,000 people with stage 1 CRC and 525,000 people with advanced precancerous lesions.
Recent U.S. Food and Drug Administration approvals of new screening tests for CRC—including Cologuard Plus, a next generation mt-sDNA test, and a new blood-based screening test—have generated headlines and discussion about their potential to further improve screening rates.
As we consider adoption of new tests into clinical practice, there are key questions we must ask. How should new screening tests be assessed? How should they be applied? And will they advance or reverse U.S. public health goals for reducing cancer incidence and mortality?
Understanding how to compare new screening tests versus existing tests is key to making an informed choice for both patients and clinicians.
Simulation models are one approach that can help assess the comparative effectiveness of different screening options. Research using a validated simulation model to assess the benefit-to-burden ratio of the Cologuard Plus test as compared to several stool- and blood-based CRC screening options was presented recently at the American College of Gastroenterology Annual Meeting.
Broad adoption of new testing strategies without a clear understanding of their limitations has the potential to reverse the progress we’ve made in advancing early detection and improvements in CRC incidence and mortality.
Paul J. Limburg
Benefit was defined as life-years gained and burden as the lifetime number of colonoscopies.
The modeling analyses show that Cologuard Plus is expected to be a highly efficient form of non-invasive CRC screening for adults ages 45-75 at average risk differentiated by its high sensitivity and specificity for both cancer and precancer.
In these analyses, blood-based screening strategies were shown to be not efficient or near-efficient at any screening interval or age-range.
It’s also important for clinicians to be familiar with the clinical trial data—including the study design—supporting each new test, and to be aware of any differences between peer-reviewed data and that used by FDA as the basis for an approval.
Best practices for study design as set forth by FDA, the National Comprehensive Cancer Network and others suggest clinical trials for new screening tests should include real-world applicability and a non-invasive test comparator.
These measures provide critical data to help determine if a new test will increase our ability to detect early-stage cancers and precancers and how it will be used or accepted by patients.
The development of innovative and accessible at-home cancer screening for patients and clinicians must begin with designing high-quality, rigorous clinical trials that produce robust results and progress the quality, accuracy, and anticipated outcomes.
Put simply, each new test needs to perform at least as well as existing options in order to have an appreciably positive impact on population health.
Broad adoption of new testing strategies without a clear understanding of their limitations has the potential to reverse the progress we’ve made in advancing early detection and improvements in CRC incidence and mortality.
Such risk is evident with any emerging test that is seen as a “replacement” for existing strategies, but without the ability to adequately detect early-stage CRCs and/or advanced precancers.
Ultimately, the goal of screening is to prevent CRC in the first place or to catch it early, when it can be treated most effectively. Blood-based test options may have the potential to expand the pool of people who are screened—though this has yet to be rigorously studied.
But the clinical data show that these tests are not as accurate as other existing non-invasive options—particularly in the detection of precancers.
Blood tests may have a role to play in closing the CRC screening gap for certain populations, but they should be applied as a second-line option.
Many experts concur, as evidenced by the multi-author commentary resulting from an expert workshop convened by the American Gastroenterology Association, which states that “while the convenience of a blood test could potentially encourage more people to get screened, expert consensus is that blood tests can’t prevent CRC… Modeling studies and expert consensus published… in Gastroenterology and Clinical Gastroenterology and Hepatology shed light on the perils of liquid biopsy.”
As new tests receive FDA approval for average-risk CRC screening, we need clear guidance from authoritative groups such as the U.S. Preventive Services Taskforce, American Cancer Society, NCCN, primary and specialty care professional organizations, advocacy groups and others to help inform and advance clinical practice.
Compared to many cancer types, we are fortunate to have effective tests for CRC screening, detection, and prevention. We must continue to innovate, while ensuring that new tests meet and improve on the current standard of care. This is how we keep moving forward, never backward.
The information provided is not clinical, diagnostic, or treatment advice. You should consult with a qualified health care professional about any questions you may have regarding a medical condition or treatment. Never disregard professional medical advice or delay in seeking it because of something you have read in this article
