Incidence and survival trends in adolescents and young adults with carcinoma of unknown primary: Insights from the SEER database (2000–2021).

e22586 Background: Carcinoma of Unknown Primary (CUP) among adolescents and young adults (AYA, ages 15–39) poses unique challenges due to diagnostic uncertainty and age-specific disparities in outcomes. This study leverages SEER data to evaluate incidence trends, survival outcomes, and mortality risks across AYA cohorts. Methods: SEER*Stat data (2000–2021) were analyzed for CUP incidence and survival in AYAs. Age-stratified cohorts (15–19, 20–24, 25–29, 30–34, and 35–39 years) were assessed for Annual Percent Changes (APC), Percent Changes (PC), and survival probabilities. Cox proportional hazards models quantified mortality risks across age and sex. Results: CUP incidence declined across all age groups, with significant reductions in the 20–24-year (APC: -3.0%, p < 0.05), 30–34-year (APC: -2.7%, p < 0.05), and 35–39-year (APC: -2.6%, p < 0.05) cohorts. Younger patients demonstrated superior survival outcomes, with a 60-month relative survival of 38.4% (15–19 years) compared to 29.7% (35–39 years). Median survival times also declined with age, from 28.0 months in the youngest cohort to 10.0 months in the oldest. Hazard ratios for mortality increased progressively with age, from 2.45 (15–19 years) to 3.59 (35–39 years), with statistically significant trends (p < 0.001). Wide confidence intervals in younger cohorts highlight data variability due to small sample sizes. Conclusions: This study highlights significant age-related disparities in CUP incidence and survival among AYAs. While incidence has declined, older AYAs continue to face poor survival outcomes, emphasizing the need for age-specific diagnostic and therapeutic strategies.