Physical activity and cancer survival: the role of peripheral blood immune and inflammatory markers in reducing mortality-a retrospective cohort study based on NHANES 1999-2018.

Background: Although clinical guidelines recommend physical activity to improve quality of life during cancer treatment, evidence regarding its association with survival-particularly cancer-specific and cardiovascular mortality-remains limited. Moreover, whether peripheral blood immune and inflammatory markers (PBIMs) are associated with this association has not been adequately explored in large, real-world cancer survivor populations. This study examined the associations between physical activity and all-cause, cancer-specific, and cardiovascular mortality in cancer survivors, and the potential role of PBIMs. Methods: This retrospective cohort study used data from 10 cycles [1999-2018] of the National Health and Nutrition Examination Survey (NHANES), linked to mortality data from the National Death Index through December 31, 2019. A total of 2,768 adult cancer survivors were included after excluding participants aged <20 years and those with missing data. Physical activity was quantified from self-reported questionnaires as metabolic equivalent (MET) minutes per week, participants were then categorized into low (<500 MET-min/week) and high (≥500 MET-min/week) physical activity levels according to the United States national physical activity guidelines. Seven PBIMs [e.g., monocyte‑lymphocyte ratio (MLR), neutrophil percentage‑albumin ratio (NPAR), and C-reactive protein-albumin-lymphocyte (CALLY) index] were calculated from routine blood tests. Weighted multivariate Cox regression, restricted cubic splines, threshold analyses, and formal mediation analyses incorporating NHANES survey weights were applied. Results: The weighted mean age was 61.9 [standard error (SE), 0.38] years; 56.9% were female. Over a median follow‑up of 100 months, 831 deaths occurred (255 cancer‑specific). After full adjustment for covariates, high ( Conclusions: Higher physical activity was associated with reduced all-cause mortality in cancer survivors, an association that was partially mediated by certain inflammatory biomarkers. These findings support the prognostic relevance of physical activity and provide preliminary evidence for the mediating role of PBIMs in long-term cancer survivors. However, causality cannot be inferred from this cross-sectional assessment of physical activity and PBIMs; prospective studies are needed to confirm these findings.