Mortality benefit of a blood-based biomarker panel for lung cancer and the PLCO cohort.

Abstract

8560 Background: A 4-protein biomarker panel (4MP) combined with the validated PLCOm2012 clinical risk model has been shown to improve lung cancer risk estimation over either metric alone. We investigated whether these panels in combination could also identify individuals at high risk of harboring a lethal lung cancer. Methods: We used data from an established logistic regression combining the 4MP and the PLCOm2012 risk model, which were assessed in pre-diagnostic sera from 552 lung cancer cases and 2,193 non-cases from the Prostate Lung Colorectal and Ovarian (PLCO) cohort. Of the 552 lung cancer cases, 387 (70%) died from lung cancer. Cumulative incidence of lung cancer death as well as sub-distributional and cause-specific hazard ratios were calculated based on 4MP+PLCOm2012 risk scores at a pre-defined 1.0% and 1.7% 6-year risk thresholds, which correspond to the 2013 and 2021 US Preventive Services Task Force lung cancer screening criteria, respectively. Results: When considering cases diagnosed within 1 year of blood draw and all non-cases, the AUC estimate of the 4MP+PLCOm2012 model for risk prediction of lung cancer death was 0.88 (95% CI: 0.86-0.90). Among cases, 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: 5.42, P: 0.02). Corresponding sub-distributional and lung cancer death-specific hazard ratios for test-positive cases were 1.69 (95% CI: 1.07-2.66) and 1.80 (95% CI: 1.15-2.82), respectively. Conclusions: The blood-based biomarker panel in combination with PLCOm2012 identifies individuals at high risk of a lethal lung cancer.