Adding a yearly liquid biopsy to standard cancer screenings could substantially cut advanced-stage diagnoses but give only a modest boost to early detection rates, according to a new simulation study.

The study, published in Cancer, estimated that — in over 10 years — annual screening with a multicancer early detection (MCED) test could lead to a 45% reduction in stage IV diagnoses of 14 cancers among Americans aged 50-84.

Many of those advanced-stage cases would shift to stage III, as the study predicted a 34% increase in stage III diagnoses. Stage I and II diagnoses would rise by an estimated 10% and 20%, respectively.

The findings suggest that routine MCED testing could “transform cancer care by reducing the number of patients diagnosed at an advanced stage,” said lead author Jagpreet Chhatwal, PhD, director of the Institute for Technology Assessment at Massachusetts General Hospital in Boston.

However, many questions remain, cautioned Carmen E. Guerra, MD, professor of medicine at the Abramson Cancer Center, University of Pennsylvania, in Philadelphia.

Guerra, who was not involved in the study, pointed to the limitations of simulation models: For one, they make assumptions about patients — such as their willingness or ability to stick with routine screening — that may not reflect reality, she said.

The estimated 45% reduction in stage IV diagnoses assumed 100% uptake and 100% adherence to yearly MCED testing for 10 years. When the researchers assumed uptake and adherence rates of 50%, the stage IV reduction was knocked down to about 24%.

But the major bigger-picture question is whether adding MCED tests to routine screening would ultimately save lives.

“That’s something we don’t really know,” Guerra told Medscape Medical News.

MCED tests detect biological signals in the blood, such as tumor DNA and DNA methylation patterns, that suggest the presence of cancer, Currently, no MCED test is approved by the FDA, but some are commercially available as laboratory developed tests, including Galleri and Cancerguard. The latter, which entered the market in September priced at $689, was the subject of the new study.

Chhatwal’s team created a simulation model to estimate the impact of adding Cancerguard testing to standard cancer screenings, using annual cancer incidence rates from the Surveillance, Epidemiology, and End Results database. While the test is designed to detect 50 cancers, the researchers focused on 14 solid tumor types that account for roughly 80% of cancers among Americans.

The analysis was designed to track a decade’s worth of simulated cancer detection results among 5 million initially cancer-free US adults aged 50-84.

Overall, the model estimated that annual MCED testing would reduce the 10-year incidence of stage IV cancer diagnoses from 2108 per 100,000 to 1159 per 100,000, relative to standard screening alone.

That would result in a small change in stage 1 diagnoses, which would rise from 3068 to 3364 cases per 100,000. Stage II diagnoses would go up from 2079 to 2491 per 100,000, while stage III diagnoses would increase the most, from 1414 to 1896 cases per 100,000. 

As for individual cancer types, the model predicted the largest absolute reductions in stage IV diagnoses would be for lung (400 vs 765 per 100,000), colorectal (96 vs 236), and pancreatic (89 vs 211) cancers. That, the researchers say, points to the potential clinical utility of MCED tests, as those cancers are among the most aggressive types.

To Chhatwal, MCED testing represents a “potential game changer in cancer screening.”

But he also acknowledged the concerns around routine use of such tests, including false positives. Even a low rate of false-positive results, Chhatwal told Medscape Medical News, could lead to “non-trivial numbers” of follow-up exams.

Guerra agreed that MCED testing holds promise. “We do know that this test can identify cancers that we have never been able to screen for before,” she said. “And that’s a big leap in the paradigm of cancer screening.” 

However, she noted that — even with the addition of MCED testing — the model suggests that many people would still be diagnosed with stage 3 or 4 cancers. And, Guerra cautioned, it cannot be assumed that a shift toward earlier detection necessarily prolongs people’s lives.

“That has been the case for the cancers we have long been able to screen for,” she said. “But more recently — with respect, for example, to ovarian cancer — we have found that not to be the case.”

“To know what this may all mean,” Guerra said, “we really need a randomized controlled trial.”

The study was funded by Cancerguard manufacturer Exact Sciences Corporation, and several co-authors are employees of the company. 

Alan Mozes is a medical journalist with 25 years of experience as a reporter for HealthDay, Reuters Health, Gannett News, and others.