Inflammation Signature Shifts Lung Cancer Screening from Smoking History to Proactive Molecular Risk

The Cell study (observational UK Biobank cohort, n=48,000, validated in eight external datasets) identifies a 14-protein plasma signature reflecting pre-malignant lung inflammation rather than tumor-derived signals, extending prediction up to five years. This builds on the 2017 CANTOS RCT (n=10,061) where canakinumab reduced lung cancer incidence but showed only modest population-level benefit; re-analysis here demonstrates benefit concentrated in high-signature individuals, dropping NNT to 55. Unlike age- and smoking-based eligibility that excludes never-smokers exposed to air pollution, the signature captures shared inflammatory states preceding lung cancer, IPF, and COPD. Limitations include reliance on observational data with potential unmeasured confounding and lack of prospective RCT validation for screening use. No conflicts disclosed in the primary report. This advances a precision-prevention paradigm but requires larger trials to confirm clinical utility.