Comparative evaluation of composite inflammatory indices for predicting prostate cancer risk and mortality: a NHANES-based study with external validation.

Background: Prostate cancer (PCa) is one of the most common malignancies in men, and chronic inflammation has been implicated in its initiation and progression. Composite inflammatory indices, based on routine peripheral blood parameters, reflect systemic inflammatory and immune status. However, their clinical utility for risk stratification and prognostic evaluation in PCa remains unclear. Methods: Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were analyzed, including 14,562 participants. Associations between 14 composite inflammatory indices and both PCa risk and all-cause mortality risk were evaluated using multivariable logistic regression and Cox proportional hazards models. Generalized estimating equations, generalized additive models, and restricted cubic splines were used to explore robustness and nonlinear associations. Kaplan-Meier survival analysis was used to evaluate prognostic associations. Furthermore, a Chinese hospital-based cohort was used for external validation of key inflammatory indices. Machine learning models were used to assess prognostic predictive performance. Results: Several composite inflammatory indices were significantly associated with PCa risk. Increased systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), and neutrophil-to-lymphocyte ratio (NLR) were related to higher PCa risk, while elevated lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), hemoglobin-albumin-lymphocyte-platelet (HALP), and monocyte-to-high-density lipoprotein cholesterol ratio (MHR) were associated with reduced risk. Restricted cubic spline analysis indicated that some inflammatory indices exhibited potential non-linear relationships with PCa incidence and all-cause mortality risk. Regarding prognosis, increased neutrophil-to-platelet ratio (NPR), systemic inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI) were associated with a higher risk of all-cause mortality, while high C-reactive protein-to-albumin ratio (CAR), creatinine-to-lymphocyte ratio (CLR), and inflammatory burden index (IBI) were linked to poorer prognosis. The external cohort further validated the stable association of SII, PLR, and NLR with adverse prognosis. Machine learning analyses yielded consistent discriminatory performance, supporting the prognostic relevance of inflammation-related hematological features. Conclusion: Multiple composite inflammatory indices are associated with the PCa risk and prognosis. Among them, SII, PLR, and NLR demonstrated stable predictive value for adverse prognosis across different populations. Inflammatory indices based on peripheral blood parameters can contribute to risk stratification and clinical decision-making for PCa patients.