Subsequent cancer risk elevated in young survivors

Adolescent and young adult cancer survivors face a substantially increased long-term risk of developing new primary malignancies, according to a population-based cohort study published in the Canadian Medical Association Journal.¹ The findings highlight the importance of sustained surveillance strategies in survivorship care, particularly beyond the 5-year postdiagnosis benchmark.

In this retrospective analysis of registry data from Alberta, Canada, investigators reported that survivors aged 15 to 39 years at initial diagnosis were twice as likely as the general population to develop a subsequent primary neoplasm. The elevated risk persisted decades after the initial cancer diagnosis and varied by cancer type and treatment exposure, underscoring the need for risk-adapted follow-up.

“When combined with the relatively high survival rates in this age range, at approximately 86%, there is a growing population of young cancer survivors that will be adversely affected by their cancer diagnosis and its treatment even decades later,” said Miranda Fidler-Benaoudia, PhD, cancer epidemiologist at the University of Calgary Cumming School of Medicine.²

Population-based data show persistent long-term risk

The Alberta Adolescent and Young Adult Cancer Survivor Study included 24,459 individuals diagnosed with a first primary malignancy between 1983 and 2017.¹ Data were derived from the Alberta Cancer Registry, which captures all incident cancers in the province. Patients were followed for a median of 7.4 years, contributing more than 250,000 person-years of observation.

The primary outcome was the development of a subsequent primary neoplasm, defined using Surveillance, Epidemiology, and End Results criteria. Synchronous cancers diagnosed within 6 months of the initial malignancy were excluded. Investigators calculated standardized incidence ratios (SIRs) and absolute excess risks (AERs) compared with the general population.

Among the full cohort, 5.9% developed at least 1 subsequent primary neoplasm. In the subset of 14,818 individuals who survived at least 5 years, 7.6% experienced a subsequent malignancy. Follow-up for this group began at the 5-year mark and continued until diagnosis of a new cancer, death, emigration, or study end.

Increased risk across cancer types and over time

After 5-year survival, the risk of a subsequent primary neoplasm was significantly elevated, with an SIR of 2.0 (95% CI, 1.9-2.2), corresponding to 35.7 excess cases per 10,000 person-years. The cumulative incidence at 30 years reached 17.7%, compared with 11.2% expected in the general population.

Breast, digestive, hematopoietic, and respiratory cancers accounted for nearly 60% of subsequent malignancies. Breast cancer was the most frequent, representing more than 1 in 4 cases. Risk patterns varied by initial cancer type. Survivors of acute lymphoblastic leukemia had the greatest relative risk, with an SIR of 4.5, while survivors of breast cancer and lymphoma had among the greatest absolute excess risks.

Treatment exposures were associated with differential risk. Regimens that included radiotherapy were linked to greater AERs, consistent with prior evidence on treatment-related carcinogenesis. Risk also increased at diagnosis and attained age, suggesting cumulative susceptibility over time.

Cumulative incidence analyses demonstrated widening gaps between survivors and the general population as time from diagnosis increased. For example, among breast cancer survivors, the absolute difference in risk grew from 2.9% at 10 years to 12.7% at 30 years.

Clinical implications for survivorship care

These findings reinforce the need for long-term, individualized surveillance in adolescent and young adult cancer survivors. Current survivorship guidelines recommend risk-based screening tailored to prior treatment exposures and cancer type. The observed heterogeneity in risk by primary diagnosis and treatment supports this approach.

The study also highlights the burden of second cancers as a leading cause of nonrecurrence mortality in this population. Clinicians should incorporate counseling on long-term risks and ensure adherence to screening recommendations.

“These findings underscore the need for innovative solutions to prevent, detect, and treat subsequent primary neoplasms among survivors of adolescent and young adult cancer,” wrote investigators.

Reference

1. Alam AU, Tchir D, McKillop S, et al. Subsequent primary neoplasm risk among survivors of cancer in adolescence and young adulthood: a population-based study from Alberta, Canada. CMAJ. 2026;198(14):E535-E549. doi:10.1503/cmaj.251381
2. Survivors of adolescent, young adult cancers at double the risk of future cancers. News release. Canadian Medical Association Journal. April 13, 2026. Accessed April 14, 2026. https://www.eurekalert.org/news-releases/1123172