Background: Cancer survivors are at an increased risk of second primary malignancies (SPMs). The risk of SPMs varies by age, with children and adolescent and young adult (AYA; 15-39 years) survivors at a higher risk of SPMs than older adults, and AYAs experiencing the highest numbers of excess cancers compared to other age groups. While prior studies reported increased mortality from SPMs among AYAs, only a few studies compared survival after a SPM to survival of the same cancer occurring as first primary malignancy (PM). We compared survival of patients with SPMs to their corresponding first PM types and determined if there were age-specific differences in survival of SPMs. Further, among AYAs, we examined whether the latency time between the PM and the SPM was associated with cancer survival. Methods: We used data from 13 Regions in the US National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program. Eligible patients were those aged 15–39 years when diagnosed with one of the 14 most common AYA malignancies during 1992–2008, with follow-up through 2013. We also included children (<15 years) and older adults (≥40 years) for comparisons. Five-year relative survival was calculated overall and for each cancer occurring as a PM or SPM by age group. The impact of SPM status on cancer-specific survival was examined using multivariable Cox proportional hazards regression. In AYAs, we also assessed whether the latency time to the development of a SPM (1–5 vs ≥6 years) influenced cancer-specific survival. Results: Across all cancers, 5-year relative survival after a SPM was 20.2% lower for AYAs, 33.1% lower for children, and 8.3% lower for older adults compared with a PM in the same age group. In AYAs, except for melanoma and testicular cancers, 5-year relative survival was worse for all SPMs compared with survival from a corresponding PM. The absolute differences in 5-year relative survival were 41.9%, 18.9%, 15.0%, and 12.6% lower for non-Hodgkin lymphoma, breast cancer, thyroid cancer, and soft-tissue sarcoma, respectively, compared with those cancers that occurred as a PM in AYA patients. In addition, cancer-specific survival was worse in AYAs with a second Hodgkin lymphoma (hazard ratio [HR] and 95% confidence interval [CI] 3.5 [1.7–7.1]); soft-tissue sarcoma (2.8 [2.1–3.9]); breast carcinoma (2.1 [1.8–2.4]); acute myeloid leukemia (1.9 [1.5–2.4]); and central nervous system cancer (1.8 [1.2–2.8]), compared with AYAs with the same PM. Among AYAs, analysis by latency time to SPM development revealed that 72.9% of SPMs were diagnosed 1–5 years after the PM diagnosis. Further, AYAs that developed a SPM within 1–5 years after diagnosis had an over 2-fold increased risk of death from cancer than those with a SPM developed ≥6 years after diagnosis (HR=2.52, 95% CI 1.92–3.29). Conclusion: SPMs adversely impact cancer survival with the risk of death being more pronounced among AYAs and children than older adults. In AYAs, there is approximately a 2-fold greater risk of cancer death in patients with a SPM compared with patients with the same PM, but no prior history of cancer. We also found that AYAs who developed a SPM within 1–5 years of their primary cancer diagnosis, the majority of patients in our study, were at an increased risk of death compared to AYAs who developed a SPM later in survivorship. As the number of young cancer survivors continue to grow, our findings highlight the importance of long-term cancer survivorship care for the prevention and early detection of SPMs. To improve outcomes after SPMs, it is important to better understand contributing factors to these findings, which may include genetic predisposition, second cancers being more biologically aggressive, a worse response to cancer therapies, limitations on the types and intensities of treatment that can be received as a result of prior cancer therapies or impaired physiologic reserves that impact ability to tolerate treatment for a second cancer.

Citation Format: Theresa H.M. Keegan, Melanie Goldfarb, Qian Li, Renata Abrahão. Second cancers and survival in adolescent and young adult cancer survivors [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr IA20.