Exploring Traditional, Experimental Screenings for Colorectal Cancer

March 13, 2023 - Colorectal cancer cases are on the rise, especially among younger patient populations. With that in mind, clinicians are looking to traditional and experimental screening tools to detect the illness with the hopes of finding a minimally invasive, accurate screening tool.

A new report published in CA: A Cancer Journal for Clinicians by the American Cancer Society (ACS) confirms trends in rising rates of early-onset colorectal cancer, or diagnosis before 50. The findings showed that the rate of colorectal cancer in individuals under 55 has increased by 1 to 2% annually since the 1990s, causing the proportion of early onset cases to go from 11% to 20% between 1995 and 2019.

Screening for colorectal cancer is key to diagnosing the condition in time for effective treatment. However, researchers and clinicians have raised additional concerns about colorectal cancer and the efficacy and utility of the current screening methods.

While there are multiple colorectal cancer screenings, including stool-based screening, endoscopy, imaging, and liquid biopsies, additional research is needed to develop accurate, non-invasive diagnostic tools.

Colorectal Cancer

The National Cancer Institute (NCI) defines colorectal cancer as cancer in the colon or rectum, often beginning with lesions in the inner lining of the colon or rectum. In 2022, ASC estimated that there were 106,180 new colon cancer diagnoses and 44,850 new cases of rectal cancer. The average lifetime colorectal cancer risk in the United States is 4 to 4.3%.

A recent statistical analysis by the ACS anticipates that there will be 153,020 new colorectal cancer diagnoses in 2023. Beyond incidence, the organization notes that it is the third deadliest type of cancer, projected to cause 52,550 deaths in 2023.

Risk Factors

The NCI explains that adults between 65 and 74 are at the highest risk of colorectal cancer; however, recent data has suggested that colorectal cancer cases in younger adults have increased across the United States.

Aside from age, multiple other factors can increase the risk of colorectal cancer, including genetic conditions, a family history of illness, obesity, a lack of physical activity, excessive alcohol consumption, tobacco use, and diet. Other conditions associated with an increased risk of colorectal cancer are inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease.

Despite theories that the recent rise in early-onset colorectal cancer cases is due to genetic and hereditary factors, the ACS notes that only 5% of new cases are due to inherited genes. This data suggests that lifestyle factors contribute more significantly to risk.

In his interview with LifeSciencesIntelligence, Mohamedtaki Tejani, MD, oncologist and director of GI Oncology at Advent Health, revealed that some researchers believed dietary patterns and a sedentary lifestyle can have increased the rate of this cancer in the US.

According to a BMJ article published in 2022, eating ultraprocessed food increases men’s risk of colorectal cancer by 29%. Additionally, certain types of processed food, including ready-to-eat/heat-mixed dishes, increased risk by 17% in women.

Colorectal Cancer Screening

Regardless of the cause of colorectal cancer, patient outcomes — like most outcomes in oncology — rely on the early detection and treatment of the condition. Diagnostic and screening tools are critical components of healthcare. This condition can be identified through multiple different screening tools.

The US Preventative Services Task Force (USPSTF) recommends that individuals begin screening for colorectal cancer at 45 if they do not have additional risk factors. Individuals at a high risk of colorectal cancer are advised to be screened earlier, at 35, and more often.

According to the CDC, multiple colorectal cancer screening tests exist; the appropriate screening test may depend on the patient’s risk factors and personal preferences. The screening tools for colorectal cancer can be divided into a few categories: stool-based tests, endoscopies, radiological tests, and blood tests.

Stool Based Screening

Stool tests are one of the least invasive ways to screen for colorectal cancer. Cologuard and other home stool tests have gained popularity for their convenience.

These tests work by detecting blood and other components in the stool, which can be expected in some patients with colorectal cancer, as polyps and other lesions in the colon and rectum can bleed. However, bloody stools may result from another condition, meaning a positive stool test must be followed up with a more accurate — usually more invasive — screening.

The FDA has approved three stool tests for screening for colorectal cancer: the guaiac-based fecal occult blood test (gFOBT), the fecal immunochemical test (FIT), and the FIT-DNA test, a multitargeted stool DNA test.

While the factors and testing protocols vary slightly between the different stool tests, the patient is usually given a stool collection kit and asked to deliver or mail the stool sample to the testing facility within 24 hours of collection. According to StatPearls, earlier delivery of the sample usually yields accurate results. 

gFOBT

The gFOBT test is used to detect heme, a component of hemoglobin, to identify if there is blood in the stool. An article published in Current Treatment Options in Oncology notes that the stool sample is smeared on a card with alpha-guaiaconic acid, oxidized in the presence of heme, yielding a blue color. This screening strategy uses three consecutive samples but only requires one positive reaction to indicate a positive test.

Additionally, since heme can be consumed through food, patients are advised to avoid certain food groups, such as red meat, before completing this test.

The primary benefits of this tool are that it is non-invasive, relatively cost-effective, and does not require uncomfortable bowel preparation. According to StatPearls, gFOBT is a reasonably sensitive test, with sensitivity ranging from 62% to 79%. Additionally, this type of screening has an 87 to 96% specificity when testing for colorectal cancer. 

Despite this screening tool's higher sensitivity and specificity, there is a major drawback. There is a risk of false positives and negatives, as the test cannot detect all polyps or cancers.

FIT

The FIT stool test builds on the gFOBT test, detecting hemoglobin in the stool. According to a publication in Nature, this type of test uses antibodies to detect human hemoglobin in the stool. The increased sensitivity and specificity of the test — 79 to 88% and 91 to 93%, respectively — allow the tests to use one sample instead of the three required for gFOBT. 

Similar to gFOBT, the benefits of FIT are that it is less invasive, cost-effective, and does not require bowel preparation. In addition, because this stool test uses a different mechanism to detect blood, it does not require that the patient restrict their diet before testing.

FIT-DNA

The FIT-DNA test, sometimes called an MT-sDNA test (multitargeted stool DNA test), is what most advertised at-home screening tests are. It is the most sensitive stool test for colorectal cancer because it looks at two components. While using FIT testing to detect blood, this screening tool also detects DNA biomarkers from cells shed and collected in the stool.

The sensitivity of this test ranges from 92% to 95%, and the specificity is  84–95%. While the FIT-DNA tests are more sensitive, it is also significantly more likely to yield a false positive. Any patient with a positive colorectal cancer stool test is advised to do follow-up testing, such as a colonoscopy.

Liquid Biopsy

The FDA has also approved a liquid biopsy to detect a SEPT9 mutation, often found in patients with colorectal cancer, to screen for colorectal cancer in adults over 50. This diagnostic tool is not recommended for patients at high risk of colorectal cancer.

Although the tool is a simple blood test, making it more convenient, there is conflicting data on its benefits. According to Nature, this screening tool is rarely used and is often a last resort screening for patients who declined other screening modalities.

Radiology

Another class of colorectal cancer screening tools is the radiological tools which require some form of imaging to detect polyps and other characteristics of colorectal cancer.

Virtual Colonoscopy

A computed tomographic (CT) colonography, also called a virtual colonoscopy, uses a CT scan to visualize the colon and rectum. After taking multiple images, the provider reviews the CT scan to identify polyps or other abnormalities.

While presenting another non-invasive solution to colorectal cancer screenings, this diagnostic tool requires colon cleansing and can miss smaller polyps. Despite the benefit of being a non-invasive procedure, if CT colonography yields a positive result, patients are typically advised to get a colonoscopy.

Double-Contrast Barium Enema

Another screening tool highlighted by the NCI is a double-contrast barium enema (DCBE). The patient is given an enema with a barium solution, and x-rays are taken to visualize the colon. The NCI notes, “The barium helps to outline the colon and the rectum on the images. DCBE is rarely used for colorectal cancer screening; however, it may be used for people who cannot undergo standard colonoscopy—for example, because they are at particular risk for complications.”

Endoscopy

While stool tests and other less disruptive tests are advantageous, endoscopy is one of the essential classes of colorectal cancer screenings.

Sigmoidoscopy

A sigmoidoscopy uses a flexible sigmoidoscope to examine the rectum and sigmoid colon. The scope is a long flexible tube with a lens inserted into the anus and rectum. After expanding the colon by pumping air into it, the provider uses the lens to visualize the lining of the colon and rectum. If the provider sees growth, they can use the tool at the end of the scope to collect a sample for biopsy.

Colonoscopy

Colonoscopies are the gold standard for colon cancer screening but are one of the most invasive screening tools. Like sigmoidoscopy, a colonoscopy uses a scope to visualize the rectum and colon. While the scope is also inserted through the anus, this screening tool allows providers to visualize the entire colon instead of just the sigmoid colon.

Ongoing Research

Although many screening tools are available for colorectal cancer, the international screening rate for those who should be screened ranges from 19 to 69%. Many clinicians and researchers attribute the low screening rate to the intensity required for accurate screening.

CTDNA Testing

One of the proposed alternatives to colonoscopy is circulating tumor DNA testing (ctDNA), a blood-based test that detects tumor DNA circulation in the blood. In an interview with LifeSciencesIntelligence, Tejani explained that there are two approaches to ctDNA testing: tumor-informed and tumor-agnostic.

The tumor-informed approach requires sequencing the tumor’s genome and detecting ctDNA based on the patient’s tumor. The tumor-agnostic method detects common mutations found in colorectal cancer.

While this tool has not been widely used, ongoing research is exploring the benefits and efficacy of using this tool to screen for colorectal cancer and monitor treatment progression.

MRI Colonography

MRI colonography has also been considered for detecting colorectal cancer. According to an article published in Nature, MRI colonography requires a patient to have bowel preparation, like CT colonography.

The MRI allows providers to visualize colorectal polyps and track metastasis in other body areas without exposing the patient to ionizing radiation. Some studies suggest that it can accurately detect colorectal cancer 98.2% of the time.

Despite the efficacy, there are some contraindications for MRI colonoscopy. Additionally, it could be a rather costly option for screening. Nature notes that additional research using larger sample sizes is needed before conclusive decisions are made on this screening tool.