Temporal trends and racial disparities in cancer-related mortality among individuals with substance use involvement in the United States, 1999–2023.

e22630 Background: Cancer-related mortality associated with substance use is an increasing public health concern in the United States and disproportionately affects vulnerable populations. However, national temporal trends and demographic disparities remain poorly defined. We evaluated subgroup-specific mortality patterns to inform targeted prevention strategies. Methods: This retrospective observational study utilized CDC WONDER mortality data from 1999–2023. Cancer-related deaths were identified using ICD-10 codes, categorized by substance use involvement based on multiple cause-of-death drug- and alcohol-induced classifications. Annual mortality counts were calculated, and temporal trends were assessed using linear and log-linear regression models to estimate slopes and annual percent change with 95% confidence intervals. Race-stratified analyses were conducted to evaluate disparities in cancer-related mortality associated with substance use involvement. Results: From 1999 to 2023, 2,179,112 cancer-related deaths involving substance use were identified in the United States. Mortality increased significantly over time. Linear regression demonstrated a strong upward trend with a slope of 6,228.8 deaths per year (95% CI: 4,242.6–8,215.1; p = 1.28×10⁻⁶), corresponding to a 1,459% cumulative increase. Log-linear modeling confirmed this rise with an overall APC of 12.8% (p < 0.001). Race-stratified analyses revealed marked disparities. Asian or Pacific Islander individuals experienced the greatest increase in mortality (APC: 15.97%; 95% CI: 11.90–20.18; p < 0.001), followed by White (APC: 12.97%; 95% CI: 8.89–17.19; p < 0.001), American Indian or Alaska Native (APC: 12.59%; 95% CI: 9.19–16.10; p < 0.001), and Black or African American individuals (APC: 12.40%; 95% CI: 8.87–16.04; p < 0.001). In contrast, White-only and Black-only subgroups demonstrated modest but significant declines (APC: −1.69% and −1.66%, respectively). Substance-specific trends differed substantially. Drug-involved cancer mortality increased most rapidly (APC: 12.40%; 95% CI: 8.56–16.38; p < 0.001), followed by alcohol-involved mortality (APC: 5.78%; 95% CI: 4.32–7.27; p < 0.001), while other substances showed smaller but significant increases (APC: 1.78%; 95% CI: 0.54–3.03; p = 0.007). Period-specific analyses demonstrated accelerated growth during 2011–2019, with no significant change from 2020–2023. Conclusions: Cancer-related mortality among individuals with substance use involvement has risen substantially over the past two decades, with pronounced racial disparities. These findings highlight substance use as a critical driver of inequities in cancer outcomes and support the need for enhanced surveillance, targeted prevention efforts, and integration of addiction-informed care within oncology to mitigate gaps.