Guardant Health's Shield: A Superior Colorectal Cancer Screening Test?

The surge in non-invasive colorectal cancer screening modalities in the past few years has been driven by the need to lower the barriers to screening that affect patient compliance. Fear, pain, discomfort — which are often unintentional — and the lack of knowledge are among the many reasons why patients delay or avoid doing a screening colonoscopy, especially if symptoms are not present.

However, it is well established that early detection and diagnosis improve the chances of successful treatment, especially if the colorectal cancer detected is still localized. While improving overall survival is a key motivation, ensuring that patients are not unnecessarily taxed mentally and emotionally is also something to strive towards.

As such, an important hallmark of a good cancer screening test is high sensitivity and specificity to the disease that the patient is being screened for. The sensitivity of a test refers to the ability to designate an individual with disease as positive. A highly sensitive test means that there are few false negative results, and thus fewer cases of disease are missed. Specificity, on the other hand, is concerned with the ability of a test to correctly identify people without the disease. A highly specific test would eliminate the likelihood of false positive results, where patients who do not have the disease are misidentified. Reducing the likelihood of false positive or negative results can benefit patients as it curbs any unnecessary anxiety or stress.

With regards to colorectal cancer screening tests that are non-invasive and high in sensitivity and specificity, Guardant Health’s Shield has recently made waves for excelling in these areas. How good is Shield as a colorectal cancer screening test, and is it the superior test compared to others?

Currently pending FDA approval, Shield is a liquid biopsy that detects the circulating tumor (sometimes called cell-free) DNA (ctDNA or cfDNA) fragments in a blood sample to screen for colorectal cancer.

ctDNA are DNA fragments that are released by tumor cells that have been shed into vascular systems and undergo apoptosis or cell death. The ctDNA found and isolated from the blood sample is then analyzed for specific DNA markers that are indicative of colorectal cancer. Guardant Health, the company behind Shield, recommends the test to asymptomatic and average-risk adults.

Compared to other screening tests like stool-based ones or scope-based visual tests, Shield has a few advantages.

For one, the test can be easily conducted during a visit to the doctor, and no preparation is required on the patient’s part. Unless one is squeamish about needles or blood, the test requires only a blood sample and is generally considered minimally invasive.

In addition, the patient does not need to handle the sample themselves, unlike the case of at-home stool test kits where patients need to collect their own stool samples for analysis.

Finally, Shield removes the need for bowel preparation or dietary restrictions. Dietary restrictions are required for stool-based tests to ensure that the compounds found in certain food do not contribute to false positive results. Meanwhile, both bowel preparation and dietary restrictions are required for colonoscopies that require the bowels to be emptied before the procedure.

While the test has not yet made its rounds with outpatient practices, the results from a pivotal study have so far been promising.

Guardant Health’s ECLIPSE (Evaluation of ctDNA LUNAR Assay In an Average Patient Screening Episode) study of 20,000 patients reported an overall 83% sensitivity. While 83% might not sound impressive — it does mean that 17% of colorectal cancer cases were not detected — the results, at more a granular level, have greater implications.

When the results are stratified by cancer stages 1 to 4, local stage 1 cancers had a reported sensitivity of 55%, while the sensitivity was 100% for stages 2, 3 and 4. This means that all the patients who had regional or advanced metastatic cancer were correctly identified. In addition, the study also reported a 90% overall specificity (i.e. 10% false positive results).

Compared to a fecal immunochemical test (FIT), which is considered the leading non-invasive colorectal cancer screening test, the overall results of the ECLIPSE study prove that Shield is potentially comparable.

Given the high sensitivity to higher-stage colorectal cancers, one might assume that Shield could potentially replace the more invasive colonoscopy procedure. However, Shield is intended as a complement to a colonoscopy. Given that the risk of false positive or negative results is not completely eliminated, a follow-up colonoscopy to verify the presence of cancer or precancerous growth is still required.

Is Guardant Health’s Shield superior to other screening tests? While the present results are promising and are shown to be comparable with other existing tests, how Shield will perform once it has been approved for outpatient use remains to be seen. Nonetheless, with high sensitivity and specificity, patients can rest assured that the likelihood of accurate results remains high, even if the outcome is not an altogether welcome one.