Early cancer detection with blood test may change cancer screening paradigms

Prepare for a significant change in early cancer detection that will impact nearly every stage of cancer diagnosis and treatment. Cancer doctors, care providers, and payers need to do this. According to Fabrice Andre, ESMO 2022 Scientific Co-Chair, new data demonstrating the reliability of multi-cancer early detection (MCED) blood tests (1), published at the ESMO Congress 2022, will have a significant impact on how cancer care is provided in the future.

"It is a duty of professional societies like ESMO to raise awareness of the fact that within the next five years, we will need more doctors, surgeons and nurses, together with more diagnostic and treatment infrastructure, to care for the rising number of people who will be identified by multi-cancer early detection tests," explained Andre, Director of Research at Gustave Roussy Cancer Centre, Villejuif, France and newly elected future president of the Society for the years 2025-2026. "We need to involve all stakeholders in deciding new pathways of care. We need to agree on who will be tested and when and where tests will be carried out, and to anticipate the changes that will happen as a result of these tests, for example in the diagnosis and treatment of people with pancreatic and other cancers that are usually diagnosed at a much later stage." Over 50 distinct cancer kinds each have a common cancer signal that new MCED tests being developed will be able to identify and pinpoint where in the body the signal originated. The sign is produced by brief segments of circulating tumour DNA (ctDNA) in the blood, which differ from non-tumour DNA in terms of methylation patterns.

In the PATHFINDER study, which was presented at the ESMO Congress 2022, an MCED test identified a cancer signal in 1.4% of 6621 adults 50 and older who were not previously diagnosed with cancer; 38% of those who had a positive test had cancer confirmed. 99.1% of the 6290 cancer-free individuals obtained a negative test result. When a test result was positive, it took a median of 79 days for a diagnosis to be made (i.e., cancer was discovered or it was determined that there was no sign of malignancy necessitating further research). 73% of participants with a positive screening test had their diagnostic issue resolved within three months.

The results demonstrated a strong detection rate for those who had cancer and a high specificity rate for those who did not, making them an essential first step for early cancer detection tests. "In patients with a positive test, it took less than two months to confirm the diagnosis if they had cancer, and it took a little longer if they did not, mostly because doctors chose to perform imaging studies and then repeat them a second-time several months later to investigate the possibility of a cancer diagnosis," said Deb Schrag, senior author of the study and from Memorial Sloan Kettering Cancer Center in New York, USA.

The fact that few participants with a false-positive screening test needed several invasive procedures like endoscopies and biopsies was a significant discovery. This finding should relieve worries that these diagnostics can hurt by necessitating unnecessary treatments in healthy individuals, continued Schrag.

While MCED tests are being developed and validated for malignancies including pancreatic, small intestinal, and stomach cancer where there are currently no screening alternatives, she emphasised the need of continuing routine screening for tumours like breast and colorectal cancer."This study suggests that there is potential for the detection of tumours that are currently undetectable, but obviously much more effort is needed, and these tests will get better with practice and larger samples. According to Schrag, the tests must be improved in order to better identify tumour DNA from all the other DNA that is circulated in the blood. It is also crucial to remember that cancer screening aims to reduce cancer mortality rather than incidence. Since mortality was not assessed in the PATHFINDER trial and necessitates extensive follow-up, it is premature to draw any conclusions on how MCED testing influences mortality.

Since prior research only employed tests in individuals who were already known to have cancer, the study presented at the ESMO Congress 2022 is the first prospective analysis to demonstrate that an MCED test can detect cancer in patients with undiscovered diseases. More research is currently being conducted, including a significant randomised clinical trial that will enrol 140,000 asymptomatic individuals in England to examine the therapeutic usefulness of MCED testing on cancer outcomes (2).

If an early detection test impacts morbidity and death, we need comparative studies across all cancer types. Additionally, we need to understand how to communicate the results with patients and how the tests help patients, said Andre. We also need to learn more about the small percentage of false positive tests, or MCED results, which suggest the presence of cancer but are not verified by conventional diagnostic techniques. Before we can estimate the financial impact of including MCED testing in standard clinical practice, we need some of these answers, Andre said.