A Blood Test Predicting Who May Benefit More From Lung Cancer Screening

Leading scientific oncology journal Journal of Clinical Oncology reported findings from a study published on 7 January 2022 showing that, when a model assessing lung cancer risk factors was combined with a new blood-based biomarker panel, lung cancer screening benefits could be predicted more specifically for individuals.

For people who have smoked for a long time and are at high risk of lung cancer, the current standard recommendation for early detection is annual low-dose computed tomography (DDBT). Previously, annual scans were recommended for people who had reached age 55 and had a 30 pack /year smoking history. With the 2021 update, everyone aged 50 with a 20 pack/year history was considered at high risk of lung cancer and recommended low-dose lung CT (US Preventive Services Task Force= USPSTF criteria).

Note: A pack-year is defined as the equivalent of smoking an average of 20 cigarettes (or one pack) a day for a year. For example, smoking 1 pack daily for 20 years equals 20 pack-years, while smoking 2 packs daily for 10 years also equals 20 pack-years. 

Among people with at least a 10 pack-year smoking history, this new combined model for predicting lung cancer risk showed sensitivity (the cancer detection rate) of 88.4%, compared with 78.5% for USPSTF criteria. Specificity was also better with the combined model (56.2% versus 49.3%).

Prof. San Hanash of the McCombs Institute for the Early Detection and Treatment of Cancer at the University of Texas MD Anderson Medical Center said, "For the first time, our study offers a blood test that may be useful in predicting who could benefit more from lung cancer screening."

The US National Lung Screening Trial previously reported that screening high-risk people with low-dose computed tomography (DDBT) reduces lung-cancer-related deaths by up to 25% (see the related study). The updated USPSTF 2021 guideline recommends DDBT screening for people between ages 50 and 80 with at least a 20 pack-year smoking history who currently smoke or stopped within the past 15 years.

Experts also emphasized that more work is needed to develop biomarkers to improve DDBT screening and better identify people who could benefit.

Hanash said, "We know that only a small percentage of people who should undergo lung cancer screening with annual low-dose CT actually do so; moreover, CT screening is not even available in most countries. For years, our goal has been first to identify the need for lung cancer screening by developing a simple blood test, thereby making lung cancer screening much more effective."

The risk model known as the control group of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial (PLCOm2012) can predict the 6-year risk of lung cancer among current or former smokers. To improve risk profiles, Hanash and the team used the 4-marker protein panel (4MP). This panel includes:

• the precursor form of surfactant protein B (Pro-SFTPB),
• cancer antigen (CA) 125,
• carcinoembryonic antigen (CEA), and
• a cytokeratin-19 fragment.

Researchers found that this 4-marker protein panel could potentially identify people at risk of developing lung cancer better than Pro-SFTB alone.

In the current study, researchers explored whether combining the blood-based 4-marker protein panel with the PLCOm2012 model could better identify people who would benefit from lung cancer screening than USPSTF criteria. They performed a validation study using data and biospecimens from the PLCO Cancer Screening Trial to assess the performance of the four biomarkers.

The combined model showed improved sensitivity with high specificity. Compared with USPSTF 2021 criteria, it showed statistically significant improvements in both sensitivity (88.4% versus 78.5%) and specificity (56.2% versus 49.3%). Among participants with at least a 10 pack-year smoking history, the 4MP + PLCOm2012 model identified 9.2% more lung cancer cases for annual screening than USPSTF 2021 criteria.

Hanash says the blood test will identify people who could benefit from lung cancer screening but are not eligible today. “Tens of millions of people worldwide could benefit from lung cancer screening. If you can improve screening eligibility by even 5%, that would have an incredibly large impact.”

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