Deficit accumulation as a predictor of lung cancer risk in older adults

Introduction: Lung cancer affects older adults, with a median age at diagnosis of 71. While low dose CT screening is recommended for high-risk smokers, 25% of cases occur in non-smokers, and few risk factors can be repeatedly assessed for early detection, especially in older adults. Age is a major cancer risk factor, and many cancer patients show accelerated biological or epigenetic aging before diagnosis, but chronological age may not reflect their true physiological condition. Deficit accumulation-a geriatric index of multisystem decline and vulnerability-may better reflect overall health than chronological age and has been reported to signal risk for age-related chronic diseases. However, its role in predicting lung cancer is unclear. We examined whether deficit accumulation predicts lung cancer beyond established predictors. Methods: We analyzed data from the linked SEER-Medicare Health Outcomes Survey (MHOS), including adults aged ≥65 who completed at least one MHOS survey between 1998-2011, followed via 2020. Incident lung cancer was identified using SEER registry data, and all-cause deaths were treated as competing events. Deficit accumulation was measured using a validated 25-item deficit accumulation index for cancer patients (range 0-1), categorized as robust (0-0.2), frail (0.2-0.5), and severely frail (>0.5). For individuals who later developed lung cancer, deficit accumulation was assessed within one year prior to diagnosis. Cause-specific Cox models estimated hazard ratios (HRs) for the association between deficit accumulation and incident lung cancer, adjusting for established predictors including age at survey, sex, smoking, body mass index (BMI), education, and prior cancer history. Variable importance metrics were used to quantify the relative contribution of model features to lung cancer risk. Results: Among 11,440 older adults, 1,011 developed lung cancer and 115 had a competing event of death before lung cancer diagnosis during follow-up. Frail and severely frail individuals had 1.45 (95% CI: 1.27-1.66) and 1.72 (95% CI: 1.40-2.12) times higher risk of developing lung cancer, respectively, compared with robust older adults. Other established predictors performed as expected, with increased risk associated with smoking and prior cancer history, and decreased risk associated with higher BMI and education. The pre-diagnostic deficit accumulation measure ranked as the third most influential predictor of lung cancer, followed by smoking history and prior cancer history. The predictive effect of deficit accumulation on lung cancer risk was more intensified among non-smokers (vs. active smokers), but interaction terms were not statistically significant. Conclusions: The 1-year pre-diagnostic deficit accumulation measure was predictive of lung cancer risk in older adults. This finding may help identify high-risk individuals who could benefit from early detection efforts.