Screening high-risk individuals with low dose computed tomography (LDCT) reduces lung cancer deaths by 20%, as per the National Lung Cancer Screening Trial (NLST) published in the New England Journal of Medicine in 2011, and several other trials. Yet, many are not eligible for LDCT screening by current guidelines.
In 2021 the US Preventive Services Task Force (USPSTF) expanded the eligibility criteria for LDCT screening. It currently recommends screening for adults between 50–80 years who have a smoking history of 20 packs a year and are currently smoking or have quit within the past 15 years. The USPSTF recognizes the need to improve the uptake of individuals for LDCT screening through research on biomarkers that enable accurate identification of people who would benefit from the LDCT screening.
“It’s been a longstanding quest for me and my team to come up with blood tests to determine who should be screened for lung cancer,” said Samir Hanash, MD, PhD, professor of clinical cancer prevention and director at the institute for the early detection and treatment of cancer at The University of Texas, MD Anderson Cancer Center.
“We recognize that a small percentage of people who are eligible for lung cancer screening through an annual low-dose CT scan are actually getting screening but CT screening is not readily available in most countries. So, our goal, for many years, has been to develop a simple blood test that can be used first to determine need for screening and make screening for lung cancer that much more effective,” said Hanash. “A blood test would identify people who could benefit from lung cancer screening but are not eligible [for screening] today. Tens of millions of people worldwide could benefit from lung cancer screening. If you can improve screening eligibility by even 5%, that is incredibly impactful.”
In a paper published in the Journal of Clinical Oncology on January 7, titled “Blood-Based Biomarker Panel for Personalized Lung Cancer Risk Assessment” Hanash and his team report they have developed blood test that measures a panel of four biomarkers. When combined with a risk prediction model for smoking history, personalized lung cancer risk assessment based on this new blood test determines more accurately than the current USPSTF recommendations, who is likely to benefit from LDCT lung cancer screening.
“We’ve shown for the first time that a simple, easy-to-implement blood test can improve assessment of lung cancer risk among smokers,” said Hanash.
The researchers conducted a multicenter, blinded validation study on 1,299 serum samples collected from 552 individuals before their lung cancer diagnosis and 8,709 serum samples from 2,193 individuals who did not develop lung cancer. All participants in the study were from the Prostrate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial with a smoking history of at least 10 packs a year.
The four-marker protein panel (4MP) evaluated in the study included the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and a cytokeratin-19 fragment. In earlier studies, Hanash and his team had identified these proteins as predictive of lung cancer risk. The risk prediction model (PLCOm2012) was independently developed and validated to predict a six-year risk for lung cancer in individuals who currently smoke or smoked earlier but had quit.
In the current study, the team compared the sensitivity and specificity of lung cancer prediction through the combined 4MP blood test and risk prediction model to the current USPSTF screening criteria. Among individuals who smoked at least 10 packs for a year, the combined blood test with risk model showed overall improved sensitivity (88.4% versus 78.5%) and specificity (56.2% versus 49.3%), compared to the current USPSTF criteria.
If implemented, the blood test in combination with the risk model would have identified 9.2% more lung cancer cases for screening among PLCO participants and reduced referral to screening among non-cases by 13.7% compared to the 2021 USPSTF criteria. In addition, the combined personalized risk assessment would have identified 105 of the 119 people in the PLCO intervention arm who received a lung cancer diagnosis within one year.
“When we began work on a blood test, there were many different types of markers. We applied in-depth profiling platforms for the discovery of biomarker candidates in the blood. The resulting biomarker panel can be implemented on current clinical platforms,” said Hanash. “We’ve done multiple analyses over the past decade to come up with a cost-effective test that’s simple, yet robust, which has been the guiding principle of our research. The test can be implemented as a lab-developed test (LDT). More validation likely will be needed for FDA approval.”
The study was funded by the National Institutes of Health, National Cancer Institute, the Cancer Prevention & Research Institute of Texas, Lyda Hill Philanthropies and MD Anderson’s Moon Shots Program.