National trends in bone-metastatic prostate cancer mortality in the United States, 1999–2024: a multiple-cause-of-death analysis with projections to 2040

Background: Conventional underlying-cause surveillance shows a declining prostate cancer mortality trend in the United States. MCOD analysis, which also includes deaths where bone metastasis was co-documented as a contributing cause, may identify a different trajectory than single-cause coding. Objective: To characterize 25-year trends in prostate cancer mortality with co-documented bone metastasis, quantify divergence from underlying-cause surveillance, and project age-adjusted mortality rates (AAMRs) to 2040 across demographic and geographic subgroups. Methods: We queried CDC WONDER (1999-2024) for deaths with prostate cancer (ICD-10: C61) as the underlying cause and bone metastasis (C79.5) as a contributing cause. Joinpoint regression characterized temporal trends, and ARIMA and exponential smoothing models with RMSE/MAPE-based selection generated stratum-specific projections. Analyses were stratified by age, race/ethnicity, US Census region, and urbanization. Results: In total, 73,429 deaths met the dual-code definition. The overall AAMR rose 93%, from 1.10 to 2.12 per 100,000 [average annual percent change (AAPC): +2.61%; 95% CI: 1.66-3.56; p < 0.000001]; however, this net increase followed an initial decline from 1999 to 2006 [annual percent change (APC): -5.57%] and reflected an acceleration to +12.91% annually during 2013-2018. Conventional underlying-cause surveillance showed an AAPC of -1.55%. Non-Hispanic Black or African American men had a mean AAMR 64% higher than non-Hispanic White men (1.89 vs. 1.15 per 100,000); in model-based projections, this ratio widened from 1.54 (2025) to 1.78 (2040). In 2024, men aged 65-85+ had a 17-fold higher AAMR than those aged 45-64. The overall AAMR is projected to reach 3.65 (95% CI: 0.88-6.43) by 2040, with wide prediction intervals reflecting substantial uncertainty. Conclusions: MCOD surveillance identified a sustained 25-year increase in co-documented prostate cancer and bone-metastasis deaths, diverging from the declining underlying-cause-only trend. The post-2013 acceleration predates the COVID-19 pandemic and persisted in sensitivity analyses. Rates were higher among older men, non-Hispanic Black or African American men, and non-metropolitan residents. As death-certificate-based measures, these estimates reflect documented bone metastasis rather than the true incidence of bone-metastatic disease and may be affected by evolving documentation and coding practices. Findings support incorporating MCOD-based metrics into national prostate cancer surveillance and targeted evaluation of care needs in higher-burden subgroups.