Early Detection of Colorectal Cancer with a Blood Test

Tests such as collecting a stool sample or preparing the bowel before colonoscopy that people find uncomfortable, avoid and postpone may be replaced in the future by a simple blood test. The new test, known as LUNAR-2, is an assay that measures circulating tumor DNA (ctDNA), and a simple blood draw is sufficient for this analysis.

At the latest annual meeting of the American Society of Clinical Oncology (ASCO 2021), researchers reporting new results said that the test could detect early-stage colorectal cancer with high sensitivity.

The results came from a study of 434 patients newly diagnosed with colorectal cancer. Overall, the blood test has 91% sensitivity and 94% specificity for colorectal cancer.

Study author Dr. Hee Cheol Kim of Samsung Medical Center, Sungkyunhkwan University School of Medicine in Seoul, South Korea, said these data were consistent with previously reported data for this blood test. "What is most notable is that there was no difference in sensitivity for detecting colorectal cancer in asymptomatic individuals compared with symptomatic patients, despite the lower cell-free DNA tumor fractions observed in asymptomatic individuals."

Current colorectal cancer screening is below the desired level

Although everyone over the age of 45 is recommended to undergo colon and rectal cancer screening such as colonoscopy or fecal occult blood testing (FOBT), awareness of this issue is not at the desired level.

Dr. Kim pointed out that current adherence to colorectal cancer screening is lower than recommended and that simpler methods are needed. "LUNAR-2 is emerging as a suitable alternative for general screening of average-risk individuals. Incorporating a blood test conducted and completed during a routine doctor’s visit into the current screening model will provide an additional screening option and will particularly encourage people who ignore or miss screening recommendations to be screened."

This prospective registration study, called ECLIPSE, is currently ongoing in the United States. Kim also added: "The primary aim is to evaluate the performance characteristics of the LUNAR-2 test for detecting colorectal cancer in average-risk individuals. Enrollment is expected to be completed at the end of 2021."

High accuracy

The LUNAR-2 test detects somatic mutations, tumor-derived epigenetic changes (such as methylation) and fragments of genetic material from cancer cells. It is a blood-based multimodal colorectal cancer detection test that uses circulating tumor DNA (ctDNA) to identify their presence.

In the study presented at ASCO 2021, the test was investigated in a group of patients already diagnosed with colorectal cancer (stages 1. - 3.) between 2013 and 2016. These individuals had agreed to provide blood samples before surgery. Neoadjuvant chemotherapy recipients were not included in the study. Control samples were obtained from 271 age-matched cancer-free individuals.

A trained model generated a dataset labeled “ctDNA detected” and “ctDNA not detected” from both people with colorectal cancer and people without cancer.

The test’s overall sensitivity is 91%. It correctly detected colorectal cancer in 393 of 434 patients; for colorectal cancer at stage 3., sensitivity was 93%, but for stages 1. and/or 2., sensitivity fell to 88%. No difference in sensitivity was observed when patients with early-onset (<45 years) or late-onset (>84 years) colorectal cancer were excluded from the analysis (90% sensitivity).

No significant difference in sensitivity was observed for asymptomatic (88%) compared with symptomatic (91%) colorectal cancer. However, higher cell-free DNA tumor fractions were detected in symptomatic patients. In addition, sensitivity was similar for right-sided and left-sided colorectal cancer (93% vs. 90%).

Validation studies are needed: Sensitivity for colorectal cancer should be higher

Commenting on the study, ASCO expert Dr. Muhammed Shaalan Beg said that although the test had very good sensitivity and specificity and there was no difference between symptomatic and asymptomatic cancer patients, "we must be very careful when generalizing these findings to healthy patients without symptoms". Dr. Beg is chief of gastrointestinal medical oncology at the University of Texas Southwestern Medical Center in Dallas. "Validation studies in large numbers of healthy people are necessary before making any claims about this blood-based colon cancer detection test" he said. "When adopting a blood-based biomarker for cancer detection, it is natural to think about sensitivity because, ultimately, we do not want to miss a cancer diagnosis."

However, Beg pointed out that in studies like these, what determines the value of the test is specificity – that is, how often is disease absent in people whose test result is negative? What other noncancerous conditions could make the test positive?

In conclusion, the value of a blood-based cancer detection tool is undeniable, but the bar is very high for colorectal cancer, especially when sophisticated stool-based tests with good sensitivity already serve this purpose. A future using both blood and stool to accurately determine personal risk can be imagined.