Mortality Benefit of a Blood-Based Biomarker Panel for Lung Cancer on the Basis of the Prostate, Lung, Colorectal, and Ovarian Cohort
Ehsan Irajizad, Johannes F. Fahrmann, Tracey L. Marsh, Jody V. Vykoukal, Jennifer B. Dennison, James P. Long, Kim‐Anh Do, Ziding Feng, Samir Hanash, Edwin J. Ostrin
Abstract
PURPOSE 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. METHODS 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. RESULTS 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 χ 2 , 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. CONCLUSION The blood-based biomarker panel in combination with PLCO m2012 identifies individuals at high risk of a lethal lung cancer.