Mortality Benefit of a Blood-Based Biomarker Panel for Lung Cancer on the Basis of the Prostate, Lung, Colorectal, and Ovarian Cohort.

Abstract

To investigate the utility of integrating a panel of circulating protein biomarkers in combination with a risk model on the basis of subject characteristics to identify individuals at high risk of harboring a lethal lung cancer. Data from an established logistic regression model that combines four-marker protein panel (4MP) together with the Prostate, Lung, Colorectal, and Ovarian (PLCO) risk model (PLCO_m2012) assayed in prediagnostic sera from 552 lung cancer cases and 2,193 noncases from the PLCO cohort were used in this study. Of the 552 lung cancer cases, 387 (70%) died of lung cancer. Cumulative incidence of lung cancer death and subdistributional and cause-specific hazard ratios (HRs) were calculated on the basis of 4MP + PLCO_m2012 risk scores at a predefined 1.0% and 1.7% 6-year risk thresholds, which correspond to the current and former US Preventive Services Task Force screening criteria, respectively. When considering cases diagnosed within 1 year of blood draw and all noncases, the area under receiver operation characteristics curve estimate of the 4MP + PLCO_m2012 model for risk prediction of lung cancer death was 0.88 (95% CI, 0.86 to 0.90). The cumulative incidence of lung cancer death was statistically significantly higher in individuals with 4MP + PLCO_m2012 scores above the 1.0% 6-year risk threshold (modified χ², 166.27; <i>P</i> < .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 PLCO_m2012 identifies individuals at high risk of a lethal lung cancer.