Cancer of unknown primary (CUP) mortality as a surrogate for imaging inequity in the United States (1999-2023)

Background: Cancer of Unknown Primary (CUP) remains a major diagnostic and clinical challenge in oncology. Despite advances in imaging, CUP continues to account for a significant number of cancer deaths in the United States. Limited access to high-quality diagnostic imaging may delay identification of the primary tumor and contribute to persistent disparities. This study examines national, regional, and demographic trends in CUP mortality from 1999 to 2023 and evaluates mortality patterns as a potential marker of imaging inequity. We analyzed national mortality data from the CDC WONDER database using ICD-10 code C80. Variables included sex, age group (15+), race, census region, metropolitan status, and state. Age-adjusted mortality rates (AAMR) were calculated for all subgroups. Temporal trends were assessed for 1999-2023. ARIMA forecasting was used to project trends to 2035. A total of 679,020 CUP deaths occurred between 1999 and 2023. The national AAMR declined from 13.24 in 1999 to 7.19 in 2023. Males had higher mortality (AAMR: 11.83) than females (8.82), though both decreased over time. Mortality was concentrated in adults aged 45 years and older. Racial disparities were marked: Black (12.09), White (10.38), and American Indian or Alaska Native populations (9.70) had nearly double the mortality of Hispanic or Latino (6.47) and Asian American or Pacific Islander groups (5.50). Nonmetropolitan areas had higher mortality (9.08) than metropolitan areas (7.84). Among regions, the Northeast (11.18), Midwest (10.55), and South (10.08) showed higher mortality than the West (8.74). ARIMA projections to 2035 suggest rising mortality for males (10.64), females (8.48), the Northeast (10.97), and the West (10.09). CUP mortality has declined nationally but remains uneven across demographic and geographic groups. Higher mortality in rural areas, high-burden regions, and populations with historically limited diagnostic access suggests that imaging inequity may contribute to persistent disparities. The rising projected mortality in select groups and regions underscores the need for targeted investments in diagnostic infrastructure, earlier access to advanced imaging, and equitable oncology services. Future research should integrate imaging and mortality data to refine strategies for early detection and intervention.