Can This Biomarker-Based Screening Identify More Early-Stage Lung Cancers?

The EarlyCDT-Lung test of several blood biomarkers was able to reduce the number of late-stage lung cancers compared to standard care in a screening trial of more than 12,000 high-risk individuals in Scotland.

“This is about targeting screening more effectively,” said Frank Sullivan, a professor of primary care medicine at the University of St. Andrews. He presented results of the new study at the International Association for the Study of Lung Cancer’s 2019 World Conference, held September 7-10 in Barcelona, Spain.

The EarlyCDT lung test includes seven antigens. These include p53, NY-ESO-1, CAGE, GBU4-5, SOX2, HuD, and MAGE A4. The trial enrolled individuals who were asymptomatic and considered at high risk for developing lung cancer; this included at least 20 pack-years of smoking history and a family history of lung cancer. All participants were between the ages of 50 and 75 years. Researchers focused on family practices in the most socioeconomically deprived quintile of Scotland. Most patients were invited to participate by their doctors, though some self-referred after learning of the trial.

The trial enrolled a total of 12,215 participants, randomized to undergo either the test (6,088 individuals) or standard care (6,121 individuals). Patients who had a positive test then underwent a CT scan at baseline and then every 6 months for 2 years.

Of the total group that received the EarlyCDT test, 598 had a positive result and underwent follow-up. The trial met its primary endpoint, with fewer late-stage cancers diagnosed in the intervention group. Among those that received the EarlyCDT test, there were 33 late-stage (stage III/IV/unclassified) lung cancers found, accounting for 58.9% of the total. In the standard care group, there were 52 such lung cancers, accounting for 73.2% of the total. This yielded a hazard ratio at 2 years favoring the test of 0.64 (95% CI, 0.41–0.99).

At the 2-year follow-up, the EarlyCDT test had a specificity of 90.4%, and a sensitivity for all cancers of 32.7% and a sensitivity for early cancers of 52.2%.

“We weren’t adequately powered for mortality, but both all-cause and lung cancer-mortality were starting to separate by two years,” Sullivan said, adding that they hope to follow the patients further to further examine mortality outcomes. “There was a 36% reduction in late-stage presentation at two years, which seems worthwhile, clinically and statistically,” he concluded.

Stephen Lam, MD, of the British Columbia Cancer Agency in Canada, who presented results of another lung cancer screening study at the IASLC conference, said that the present guidelines put forth by the U.S. Preventive Services Task Force for screening are increasingly inadequate.

“It is now known that using the U.S. Task Force criteria based on age and smoking history, a decreasing number of people would be eligible for screening, because more people have stopped smoking, and people who are still smoking smoke less than before,” he said during a press conference. “That’s why we need a better prediction model to identify people who would benefit from lung cancer screening.”          

Sullivan agreed, saying that the next steps for lung cancer screening will involve determining what combination of biomarkers - like those used in the EarlyCDT test - and other factors will identify the best group of individuals to benefit from lung cancer screening.