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.