Subsequent Primary Neoplasms and Mortality Among Survivors of Childhood Cancer in Alberta, Canada

Background: While research shows childhood cancer survivors experience elevated subsequent primary neoplasm (SPN) and premature mortality risks, few studies have included contemporary survivors. Methods: This study quantifies the risk of SPNs and mortality among modern survivors of childhood cancer. Utilizing a retrospective, population-based cohort of individuals diagnosed with cancer before the age of 18 in Alberta, Canada (2001–2018), we evaluated their risks of SPNs and mortality compared to the general population in Alberta, overall and after 5-year survival, using standardized mortality and incidence ratios, and absolute excess risks per 10,000 person-years. Results: Among 2581 survivors, including 1385 5-year survivors, 50 individuals developed at least one SPNs and 408 deaths were observed, with 21 SPNs and 38 deaths occurring after 5-year survival. The SPN incidence was 13.3- (95% CI: 9.8–17.5) and 10.0-fold (95% CI: 6.2–15.2) higher than expected overall and in 5-year survivors, respectively, with risks varying depending on the treatment received. For mortality, survivors experienced 62.5-fold (95% CI: 56.5–68.8) higher mortality than expected overall, equating to 233.9 (95% CI: 210.8–257.0) excess deaths per 10,000 person-years, with corresponding risks among 5-year survivors at 10.9 (95% CI: 7.7–15.0) and 43.8 (95% CI: 28.4–59.1), respectively. The excess deaths were predominantly due to recurrence/progression (89.9% overall, 66.4% in 5-year survivors), with SPNs and non-neoplastic causes contributing more excess deaths with increasing follow-up time. Risks for mortality included treatment and cancer type. Conclusions: Contemporary childhood cancer survivors in Alberta experience substantial excess SPNs and mortality, highlighting the need for long-term surveillance and tailored risk mitigation interventions.