The burden of long-term complications among adolescent and young adult cancer survivors: An international comparison of two large cohorts.

Background: There is a paucity of information on health outcomes of adolescent and young adult (AYA) cancer survivors outside of Northern Europe or North America. We compared long-term health outcomes of Israeli AYA cancer survivors to non-cancer individuals with similar demographics and access to healthcare, estimated the risk of developing chronic health conditions by cancer type, and compared the comorbidity burden in Israeli AYA survivors to AYA cancer survivors from the U.S. Methods: This was a retrospective cohort of 2-year cancer survivors diagnosed with invasive cancer between 15 to 39 years of age from 2000 to 2018 in Clalit Health Services (CHS), the largest payer-provider healthcare organization in Israel. Non-cancer CHS participants were matched 4:1 to cancer survivors on age, sex, ethnicity, and membership duration. Health conditions were limited to those requiring medical intervention. Incidence rates for health conditions were determined for the two cohorts, and Poisson regression was used to determine the incidence rate ratio (IRR) with associated 95% confidence intervals (CI). A sub-population of CHS AYA survivors was used to compare the incidence of chronic health conditions from the Israeli cohort to AYA cancer survivors from Kaiser Permanente Southern California (KPSC), using Standardized Incidence Rate (SIR). Results: There were 12,674 CHS AYA cancer survivors and 50,696 non-cancer participants. Among survivors, the mean age at diagnosis was 31.02 years (SD: 6.2), 61.7% were female, and 78.4% were Jewish. The most common cancer diagnoses were lymphoma (16.5%), breast (16.4%), and thyroid (14.0%). Cancer survivors were significantly more likely to have any (IRR 1.60 95%CI: 1.54-1.67) or multiple (IRR 1.82 95%CI: 1.72-1.94) chronic health conditions compared to non-cancer participants. Survivors had an increased risk across nearly all examined outcomes, with an especially higher risk for premature ovarian failure (IRR 6.02 95%CI: 2.14-16.91), osteoporosis (IRR 4.74 95%CI: 4.06-5.53), and cardiomyopathy (IRR 4.20 95%CI: 3.35-5.27). We also found clear differences in the risk of specific health conditions by cancer type. Compared to the KPSC cohort, CHS cancer survivors had an overall lower (SIR 0.82 95%CI: 0.79-0.84) incidence of developing any health condition, with noticeably lower incidences of hypertension, hyperlipidemia, chronic liver disease, but higher incidences of cardiopulmonary diseases and osteoporosis. Conclusions: AYA cancer survivors in Israel are at increased risk for developing chronic conditions, compared matched non-cancer individuals, but the overall incidence of was lower when compared to survivors living in the U.S. These findings may allow for refinement of surveillance recommendations for AYA survivors, taking into consideration regional differences in socio-demographics and cancer care.