Blood Test Improves Selection for Lung Cancer Screening in Long-Term Smokers

Senior male smoking cigarette on black background

Researchers at The University of Texas MD Anderson Cancer Center have developed a simple blood test that could transform the way people are selected for lung cancer screening.

The current U.S. Preventive Services Task Force (USPSTF) 2021 guidelines recommend screening with low-dose computed tomography (CT) for people who are 50 to 80 years of age, have at least 20 pack–years of smoking history (i.e. they have at least one pack of cigarettes per day for 20 years), and are either current smokers or have quit within the past 15 years.

However, the guidelines were released with a recommendation for further research to improve screening uptake and identify biomarkers that could more accurately detect people likely to benefit from screening.

Sam Hanash, professor of Clinical Cancer Prevention at MD Anderson, and colleagues, have developed one such test.

The four-marker protein panel (4MP) includes four proteins—the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19 fragment—that have previously shown potential to identify people at risk of developing lung cancer.

When used in conjunction with a validated lung cancer prediction model (PLCOm2012), the 4MP shows greater sensitivity and specificity for lung cancer than the USPSTF 2021 criteria, reported Hanash and co-authors in The Journal of Clinical Oncology.

The team tested the performance of the 4MP in 1299 blood samples collected from 552 individuals who developed lung cancer up to 6 years later and 8709 samples from 2193 people who did not and found that the blood test accurately distinguished between the two groups 72% of the time.

This increased to 85% when the 4MP was combined with the PLCOm2012 risk prediction model and tested on samples collected in the year preceding diagnosis from individuals with at least 10 pack–years of smoking (98% of the cohort).

The accuracy of The PLCOm2012 model alone, which predicts a 6-year risk of lung cancer among current or former smoker based on individual characteristics, was significantly lower, at 80%.

Compared with USPSTF 2021 criteria, the combined 4MP plus PLCOm2012 model had greater sensitivity (88.4% versus 78.5%) and specificity (56.2% versus 49.3%) for identifying individuals who would benefit from CT screening.

This improved performance would have resulted in 9.2% more cases being referred to screening as well as 13.7% fewer cases receiving a referral.

Speaking to Inside Precision Medicine, Hanash said that the 4MP test could change the future of lung cancer diagnostics because it means “a blood test would be a prelude to screening for lung cancer among individuals who are not eligible or individuals who are eligible but not sure they want to do CT screening.”

He also noted that in many countries outside of the U.S., CT screening is not typically implemented “so a simple blood test to determine need for screening would justify CT screening for individuals deemed at risk after getting the blood test.”

Hanash and team are now looking into deploying the test more widely but may first need approval from the U.S. Food and Drug Administration. On the basis of previous studies and modelling analyses they believe that a combined biomarker and low-dose CT screening strategy would be cost-effective.

Hanash said that the take home message from the study is that “blood testing can improve lung cancer screening and detection, and more generally, that blood tests can be useful to tailor screening for common cancers based on their blood biomarker profile.”

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