Abstract

Background: The value of physical activity for prognosis and its underlying mechanisms in cancer survivors remain incompletely understood. This study aimed to investigate the associations between physical activity and all-cause, cancer-specific, and cardiovascular mortality in cancer survivors, and to assess whether these associations are mediated by a panel of peripheral blood immune/inflammatory markers (PBIMs).
Methods: This population-based cohort study included 2,768 adult cancer survivors from ten cycles (1999-2018) of the National Health and Nutrition Examination Survey (NHANES). Physical activity was quantified from questionnaire data and categorized into low and high levels based on established guidelines. Seven PBIMs were calculated from laboratory data. Weighted multivariable Cox proportional hazards models were used to assess the prognostic value of each indicator. Restricted cubic splines were used to characterize nonlinear relationships, with threshold analysis applied where appropriate. Mediation analyses were conducted to estimate the proportion of the physical activity-mortality relationship explained by the PBIMs.
Results: Compared to the low physical activity group, participants with high physical activity demonstrated significantly reduced risks of all-cause mortality (hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.59-0.79) and cardiovascular mortality (HR, 0.69; CI, 0.50-0.96). High physical activity was significantly associated with favorable levels of most inflammatory markers, including the C-reactive protein-albumin-lymphocyte (CALLY) index, monocyte-to-lymphocyte ratio (MLR), and neutrophil percentage-to-albumin ratio (NPAR). Notably, the CALLY index and MLR significantly mediated the association between physical activity and all-cause mortality, with mediation proportions of 8.95% and 10.49%, respectively.
Conclusion: Higher physical activity is associated with reduced all-cause mortality in cancer survivors, which partially mediated by improved specific inflammatory biomarkers. These findings confirmed the prognostic value of physical activity and revealed the mediating role of PBIMs in a larger cohort of long-term cancer survivors.

Keywords

Physical activity, C-reactive protein-albumin-lymphocyte index, cancer survivors, mediation analysis, NHANES