A New Blood Test Detects Precancerous Colorectal Adenomas

A new blood test shows promise for the early diagnosis of colorectal cancer(cancer of the large bowel).

The "multinomic" test being developed by the biotechnology company Freenome has previously been shown to detect early-stage (stages I and II) colorectal cancer with 94% sensitivity and 94% specificity.

A new study shows that it can also detect precancerous lesions, colorectal advanced adenomas (advanced adenomas = AA).

What Is a Colorectal Adenoma?

Colorectal adenomas are progressive premalignant (precancerous) epithelial lesions that may show low- or high-grade dysplasia. Colorectal cancers spread beyond the muscularis mucosae, at least into the submucosa, and arise from adenomas with high-grade dysplasia.

Advanced adenomas are defined by any of the following features:

• ≥ 1 cm,
• multiple (≥ 3),
• high-grade dysplasia or
• any villous structure

People with advanced adenomas have a 3-5-fold higher risk of colorectal cancer than the population average.

Early Diagnosis of Advanced Colorectal Adenomas with a Blood Test

Being able to detect advanced adenomas is incredibly important because it allows us to remove them before they become cancerous.

At the Gastrointestinal Cancers Symposium (GICS) 2021, data were presented showing that the new test could detect advanced adenomas with 41% sensitivity and 90% specificity.

This sensitivity of the new test is better than or similar to currently available stool tests (see 7 Alternatives to Colonoscopy for the Early Diagnosis of Colon and Rectal Cancer).

The new test had almost twice the sensitivity of the fecal immunochemical test (FIT) for detecting advanced adenomas (41% versus 24%), and its sensitivity was comparable to that of the FIT-DNA test (41% versus 42%).

What makes this technique special is the use of a multinomic technology; in other words, DNA, RNA, proteins and other biomarkers are examined together.

This omic technique provides a multidimensional view of both tumor- and immune-derived biomarkers that enables early cancer detection, using advanced computational biology and machine learning techniques to integrate assays for cell-free DNA, methylation and circulating proteins.

Unlike other approaches being developed for early cancer detection, including some claiming to detect several common cancer types with liquid biopsy tests, Freenome focuses solely on colorectal cancer. Other companies also work in early detection, but some screen for multiple cancers and have a generalized product. This new approach targets early diagnosis of colorectal cancer, the 3rd most common cancer worldwide, in order to focus on a particular cancer type, and the company says it will subsequently expand to other types.

Better Sensitivity in Early Diagnosis

The study presented at the meeting evaluated the new multiomic blood test for detecting advanced adenomas.

Blood samples were taken from participants in AI-EMERGE, a prospectively collected multicenter study involving average-risk screening patients at 30 hospitals in the United States and Canada. The study included a total of 542 samples, comprising 122 histopathologically confirmed advanced adenomas and 420 colonoscopy-confirmed negative control samples.

The new test's sensitivity for detecting advanced adenomas was higher than that of the mSEPT9 test, currently the only blood test available for colorectal cancer screening. Its sensitivity was much higher than FIT's and comparable to FIT-DNA's. In the abstract, the authors described increasing sensitivity with increasing lesion size and consistency across location and histology, except for serrated lesions.

By combining biological signatures (markers) from both tumor and non-tumor sources, the multinomic approach detects twice as many advanced adenomas as methylation-only or single-protein approaches. It has now been shown that sensitive detection of advanced adenomas can be achieved in blood at a level similar to or better than currently available stool testing, which is necessary for effective early detection and prevention of colorectal cancer.

The company has begun the regulatory process to have the test approved by the FDA. Its goal is to enroll 14,000 participants and collect data prospectively.