Abstract B022: Trends in the Cumulative Incidence of Second Primary Cancers Among Survivors of Early-Onset Cancer in the United States, 1975-2022

Introduction: Survivors of a first primary cancer (FPC) have a higher risk of developing a second primary cancer (SPC) compared to the general population, potentially driven by shared etiologic factors, genetic susceptibility, treatment-related effects, or heightened surveillance and screening. However, this elevated risk has not been well-characterized in the context of the rising incidence rate of adult early-onset cancers. Methods: Using data from 9 cancer registries in the U.S. from 1975 to 2022 in the Surveillance, Epidemiology, and End Results (SEER) Program, we estimated 5-year cumulative incidence of invasive SPC among those diagnosed with invasive FPC and the average annual percent change (AAPC) by age at FPC diagnosis (18-29, 30-49, 50-59, 60-69, 70-79, 80+), and examined these trends by sex and race/ethnicity. Results: Among FPC survivors, the age-standardized 5-year cumulative incidence of SPC steadily increased from 4.10 [3.90, 4.29]% to 6.54 [6.38, 6.69]% with AAPC of 1.12 [1.03, 1.20]% during the study period. The cumulative incidence increased across all age groups at FPC diagnosis. Among early-onset cancer survivors (i.e., those with FPC diagnosis at age 18-49 years old), female individuals had a higher SPC cumulative incidence than male individuals over the study period. However, the increase over time was steeper among males (e.g., for age 30-49 years old, AAPC: 1.59 [1.20, 1.98]% vs. 0.57 [0.37, 0.78]%), making the cumulative incidences similar in males and females by the end of the study period. Among those with FPC diagnosis at age 30-49 years old, the SPC cumulative incidence increased for all racial/ethnic groups, but the increase was steeper for Hispanic and non-Hispanic (NH) Asian or Pacific Islander (API) individuals compared to NH Black and NH White individuals. Notably, NH API individuals had a higher AAPC at this age group than at older age groups, a pattern unique to this racial/ethnic group. Among those with FPC diagnosis at age 18-29 years old, the trends were inconsistent across racial and ethnic groups, with positive AAPC for NH White individuals (1.93 [1.35, 2.51]%) and negative AAPC for Hispanic individuals (-2.59 [-4.26, -0.89]%). Conclusion: For nearly five decades, the burden of SPC following early-onset cancer has risen steadily across demographic groups. These trends suggest a compounded burden of cancer for more recent generations, who face an elevated risk of both an early-onset first cancer and a subsequent cancer, which may also occur at a young age. Potential drivers of these patterns, including improved survival, harmful treatment effects, and other etiologic factors, should be investigated in future research. Citation Format: Sunyeop Lee, Erica J. Lee Argov, Parisa Tehranifar. Trends in the Cumulative Incidence of Second Primary Cancers Among Survivors of Early-Onset Cancer in the United States, 1975-2022 [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr B022.