Background/Objectives: This population-based study examined epidemiological trends of primary cancers in adolescents and young adults (AYAs) to enhance the understanding of the specific spectrum of cancers impacting AYAs in Belgium. Methods: Data on incidence, prevalence, mortality, and survival were obtained from the Belgian Cancer Registry (2004–2020, N = 43,535). (A)APC statistics were compared with children (5–14 years) and adults (40–49 years). Results: Cancer incidence increased by 0.4% annually from 66 to 80 per 100,000 person-years (ESR2013) but stabilised after 2015, except for Hodgkin lymphoma, chronic myeloid neoplasms, and testicular and breast cancer, which continued to rise. Mortality decreased by 1% annually, from 10 to 7 per 100,000 person-years (2004–2019). Five-year relative survival (RS) was 87% but remained low for certain cancers, including ovary (78%), central nervous system (67%), precursor haematopoietic neoplasms (64%), gastrointestinal (excl. colorectal) (49%), and lung-bronchus-trachea cancers (42%). Conclusions: From 2004–2020, the cancer burden among AYAs in Belgium increased due to improved survival, while incidence stabilised after 2015. Five-year RS exceeds 80% overall but remains lower for some cancers compared to children (e.g., precursor haematopoietic neoplasms) or older adults (e.g., breast cancer, sarcoma). The Belgian epidemiological trends align with those in neighbouring countries (Netherlands, France, Germany).
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