Researchers at the University of Texas MD Anderson Cancer Center have developed a blood-based test that can predict an individual’s risk of dying from lung cancer when combined with a personalized risk model. According to a study “Mortality Benefit of a Blood-Based Biomarker Panel for Lung Cancer on the Basis of the Prostate, Lung, Colorectal, and Ovarian Cohort” in the Journal of Clinical Oncology, a blood-based four-protein panel (4MP), when combined with a lung cancer risk model (PLCOm2012), can better identify those at high risk of dying from lung cancer than the current U.S. Preventive Services Task Force (USPSTF) criteria.
These findings build upon previous MD Anderson research demonstrating the combination test more accurately determined who is likely to benefit from lung cancer screening than the USPSTF criteria.
“When considering cases diagnosed within 1 year of blood draw and all noncases, the area under receiver operation characteristics curve estimate of the 4MP + PLCOm2012 model for risk prediction of lung cancer death was 0.88 (95% CI, 0.86 to 0.90),” write the investigators. “The cumulative incidence of lung cancer death was statistically significantly higher in individuals with 4MP + PLCOm2012 scores above the 1.0% 6-year risk threshold (modified χ2, 166.27; P < .0001). Corresponding subdistributional and lung cancer death–specific HRs for test-positive cases were 9.88 (95% CI, 6.44 to 15.18) and 10.65 (95% CI, 6.93 to 16.37), respectively.
“The blood-based biomarker panel in combination with PLCOm2012 identifies individuals at high risk of a lethal lung cancer.”
“This simple blood test has the potential to save lives by determining the need for lung cancer screening on a personalized basis,” said co-corresponding author Samir Hanash, MD, PhD, professor of clinical cancer prevention. “Given the challenges associated with CT as a frontline screening method for lung cancer and the fact that most individuals diagnosed with the disease do not meet current guidelines, there is an urgent demand for an alternative approach.”
Pre-diagnostic blood samples
For this study, MD Anderson researchers analyzed pre-diagnostic blood samples from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial, including 552 individuals who later developed lung cancer and 2,193 who did not. Of the 552 individuals diagnosed during the six-year study period, 70% (387) died from lung cancer.
Using hazard ratios, the researchers assessed the relationship between the risk scores generated by the combination model (4MP + PLCOm2012) and the incidence of lung cancer death. The combination showed improved sensitivity, specificity and positive predictive value compared to the 2013 and 2021 USPSTF criteria for predicting lung cancer-specific mortality among individuals who smoked at least 10 pack-years (PYs).
The USPSTF recommends that adults at elevated risk for lung cancer receive a low-dose CT scan each year, which was shown to reduce lung cancer deaths in the 2011 National Lung Screening Trial (NLST). The 2021 USPSTF criteria applies to adults aged 50 to 80 who have at least a 20 PY smoking history and currently smoke or have quit within the past 15 years.
“For individuals who currently are not eligible for lung cancer screening, a positive test may help to identify those possibly at risk for lung cancer death,” said co-corresponding author Edwin Ostrin, MD, PhD, assistant professor of general internal medicine. “We envision this as a tool that could be deployed worldwide, as the future of early detection of this disease.”
Lung cancer causes an estimated 25% of cancer deaths. Early detection improves prospects of survival, but most countries do not screen for it. Fewer than half of all U.S. cases are among people who are eligible under USPSTF guidelines.
While the blood test could be implemented as a lab-developed test in the near future, FDA approval likely would require evaluation through a prospective clinical trial.
Hanash is an inventor on a patent application related to the blood test. A complete list of co-authors and their disclosures is included in the paper.
