For colorectal cancer, the only good screening test is one that is taken

Tests for detecting hidden (“occult”) blood in stool is widely available

Screenshot from USPSTF CRC screening video

We have discussed before the challenge of raising colorectal cancer screening rates, and the fact that there are many options in addition to the outpatient colonoscopy procedure. A common quote is ‘the best test is the one that gets done’, because it is true. With over dozens fecal immunohistochemical tests (FIT) on the market, and even more guaiac-based Fecal Occult Blood Tests (gFOBT), part of the issue is physician education, and another part is public awareness.

As colorectal cancer is the second-leading cause of cancer death in the United States (140,000 new cases in 2018, and over 50,000 deaths), these numbers could become drastically lower if current screening guidelines were adhered to at higher than the estimated 64-67% in the target group of 50 to 75 years of age. With about 92 million American adults in this age group, about 30 million American adults could be cured of colorectal cancer if found early enough, and the key to early detection is screening.

Colorectal cancer screening does not necessarily involve a colonoscopy. One method is detecting blood in the feces on an annual basis, and one type of test using an antibody-based detection method is called FIT.

Results from a meta-analysis of 120,000 participants

A recent study (Imperiale et al Reference) examined no less than 31 individual studies using FIT and combined their results, with a total of 120,255 participants across 18 FIT test manufacturers. While the performance characteristics of these tests were dependent on the threshold chosen (for FIT this is measured in ugram / gram), when set at a higher level (specifically 20 ug/g) the overall sensitivity was measured to be 0.91 (95% Confidence Interval 0.84 to 0.95).

Sensitivity for advanced adenoma, a precursor to Stage I colorectal cancer in an estimated 85% to 90% of the cases where advanced adenoma is detected, was much lower at 0.40 (95% CI 0.33 to 0.47).

The authors conclude, “Single-application FITs have moderate to high sensitivity and specificity for CRC, depending on the positivity threshold. Sensitivity of 1-time testing for advanced adenomas is low, regardless of the threshold.”

Tests can even be ordered online

One company Biomerica Incorporated has received over-the-counter (OTC) approval from the US FDA for the ‘EZ Detect Colon Disease Test’. What is unique about this test format is its simplicity: it is a package of four test papers and a small packet of a positive control.

The first paper, thrown into an empty toilet, is a negative control to ensure that the water quality will not throw any false-positive result. The next three papers are to be used after three consecutive bowel movements, by simply placing them in the toilet water and looking for a blue indicator to show up with a large ‘plus’ sign (indicating a positive result). After the third presumably negative result, the positive control packet is dissolved into the water, with the bright blue plus sign confirming the test working as it should.

Through ease-of-use (no handling of stool) and widely available through distribution via Walgreen’s pharmacies and even online at Amazon, this is a method that reduces the unpleasantness for other stool-based tests that is a barrier to wider adoption. It is also relatively inexpensive at $12 to $15 per test.

Calling a colonoscopy a gold standard “is not helpful or true”

Writing an editorial in the same Annals of Internal Medicine issue with a piece called “Why what you may not know about fecal immunohistochemical testing matters” < https://www.ncbi.nlm.nih.gov/pubmed/30802903> Dr. James Allison (UCSF) is quoted in a followup interview in Medscape Medical News  https://www.medscape.com/viewarticle/909568#vp_2 with the following.

We've got to get away from the idea that there's only one good test for colon cancer screening. We must increase our national screening for CRC numbers, especially in the vulnerable population — the uninsured, underinsured, poor. Calling a colonoscopy screening test the best, or the gold standard, is not helpful or true. It's a good test, and I'm not saying don't have a colonoscopy. I'm saying don't limit yourself to colonoscopy because it's called the best or gold standard by some.

He continues by pointing out that the current USPSTF guidelines that both FIT and gFOBT screening tests are ‘right up there with colonoscopy’ in terms of recommendations.

A problem of awareness, education, and compliance

For many average-risk individuals age 50 to 75, colonoscopy is often the only recommendation offered by their health-care professional, with non-invasive stool-based testing on offer only if colonoscopy is rejected as an option. Direct-to-consumer marketing, namely Exact Science’s Cologuard Test, does increase awareness of non-invasive options for screening, and outside the United States stool-based testing is preferred but also suffers from low compliance rates.

At Singlera Genomics we are working toward getting a blood-based ColonES colorectal cancer screening assay to market. And we cannot overemphasize the importance of staying current with your individual screening status.

References:

1. Imperiale TF and Monahan PO et al. Ann Intern Med. 2019 Performance Characteristics of Fecal Immunochemical Tests for Colorectal Cancer and Advanced Adenomatous Polyps: A Systematic Review and Meta-analysis. PubMed PMID: 30802902. https://www.ncbi.nlm.nih.gov/pubmed/30802902
2. Allison J. Ann Intern Med. 2019 Why What You May Not Know About Fecal Immunochemical Testing Matters. PMID: 30802903. https://www.ncbi.nlm.nih.gov/pubmed/30802903