Early Detection of Cancers Is Feasible with Blood-Based Tests

August 2020 Vol 11, No 8

Categories:

Early Detection

Two studies presented at the 2020 virtual meeting of the American Association for Cancer Research confirm the value of liquid biopsy in the early detection of cancer.

In one of the studies, a cell-free DNA (cfDNA) test in persons with suspicion of cancer yielded a negative (for cancer) result for all participants in the noncancer group, and a positive (for cancer) result in 40.2% of the participants in the cancer group. In addition, the test was efficient in identifying the tissue of origin in the cancer group.

In a separate first-of-its-kind prospective study of a multicancer blood test (DETECT-A) to screen 10,000 women with no history of cancer, the test identified 10 different cancer types, and 65% of the cancers detected by the test were early stage. When combined with standard-of-care screening, the number of cancers detected could be doubled, according to the investigators.

cfDNA Detects >50 Types of Cancers

The Circulating Cell-free Genome Atlas (CCGA) study is a multicenter, case-control, observational study of a cfDNA multicancer early detection test with longitudinal follow-up of 15,254 participants with a clinical suspicion of cancer who did not yet have a confirmed diagnosis. Planned follow-up is 5 years.

A single blood sample is collected at the point of care. The test is designed to detect the presence or absence of multiple lethal cancer types, including cancer types without screening paradigms, as well as to predict the tissue of origin appropriately to direct the diagnostic workup.

The study was divided into 3 substudies: a discovery substudy (substudy 1), an assay refinement substudy (substudy 2), and further assay validation (substudy 3).

In CCGA substudy 1, a methylation-based assay was found superior to targeted sequencing and whole genome sequencing approaches and was therefore selected for further development.

David D. Thiel, MD

CCGA substudy 2 was conducted with the methylation assay in patients with confirmed pathologic diagnosis or a high suspicion of cancer. In this substudy, “more than 50 cancers were detected at a specificity of over 99%,” said lead investigator David D. Thiel, MD, urology specialist at Mayo Clinic Florida, Jacksonville. “Tissue of origin was predicted in 96% of samples with cancer-like signal. Of those, the tissue of origin localization was accurate in 93% of the cases.”

The performance of the test was then evaluated in a subgroup of 303 patients from CCGA substudy 2 with a high clinical suspicion of cancer but without a confirmed pathologic diagnosis at the time of enrollment. Cancer status was confirmed within 6 weeks after study blood draw by evaluating a pathologic specimen. Those confirmed to have cancer included participants with multiple types of cancers across all cancer stages. In this subgroup, specificity of the multicancer early detection blood test was 100%. “High specificity, although with small sample size, suggests that the false-positive rate was not elevated in individuals with high risk versus the enrolled population,” he said.

In the subgroup with high clinical suspicion, sensitivity for all cancers was 40.2% in the training set and 46.7% in the validation set. The tissue of origin prediction accuracy in this subgroup was 85.5% in the training set and 97.1% in the validation set. Both sensitivity and prediction of tissue of origin were comparable to the sensitivity and tissue of origin prediction found in CCGA substudy 2.

“This test is intended to be used alongside guideline-recommended screening and not replace it,” said Dr Thiel.

DNA and Protein Test Doubles Cancer Detection When Used with Screening

The DETECT-A multicancer liquid biopsy test incorporates DNA and protein markers to detect cancer. It was evaluated in 10,006 women 65 to 75 years old who had no history of cancer. All patients with blood tests positive for cancer underwent diagnostic PET-CT scans to detect and localize the putative cancer.

An interim analysis showed that DETECT-A could identify 10 different cancer types, and 65% of the cancers detected were classified as local or regional disease, reported Nickolas Papadopoulos, PhD, professor of oncology and pathology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore. The positive predictive value of the blood test alone was 19%, which is higher than existing noninvasive screening tests for individual cancers. When combined with standard-of-care screening, the number of cancers detected was doubled.

Of the 10 different cancer types detected, 7 do not have standard-of-care screening, he said. Furthermore, performing the blood test did not incur a large number of futile invasive follow-up tests as “close to 99% of individuals did not undergo any procedure.”

Dr Papadopoulos concluded that “it is feasible for a minimally invasive blood test to safely detect several types of cancers in patients not previously known to have cancer, enabling treatment with intent to cure in at least a subset of individuals.”

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Last modified: August 10, 2023

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