Approximately one in six adolescents and young adults who survive cancer will be diagnosed with another cancer within 30 years of their initial diagnosis, making their cancer risk more than double that of the general population, shows data from Canada.
“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,” write Miranda Fidler-Benaoudia, a cancer epidemiologist at the University of Calgary Cumming School of Medicine and Cancer Care Alberta, and co-authors in the Canadian Medical Association Journal.
“Given that subsequent primary neoplasms are major contributors to morbidity and premature mortality, these findings underscore the need for innovative solutions to prevent, detect, and treat subsequent primary neoplasms among survivors of adolescent and young adult cancer,” they say.
Although global data suggest that adolescent and young adult cancer survivors are 1.6 to 4.3 times more likely to develop a subsequent cancer than expected in the general population, data are limited for Canada, where cancer rates among this group increased annually by 1.3% from 1998 to 2012, with an estimated 8739 adolescents and young adults diagnosed with cancer in 2022.
The Alberta Adolescent and Young Adult Cancer Survivor Study retrospectively reviewed data for 24,459 people with a neoplasm first diagnosed between 1983 and 2017 at age 15 to 39 years. Of these, 1442 (5.9%) had subsequent primary neoplasms, 1129 (7.6%) of which occurred among the 14,818 people who were five-year survivors.
The researchers report that, overall, adolescent and young adult cancer survivors were 2.2 times more likely to develop a subsequent primary neoplasm than would be expected in the general population, equating to 31.7 excess neoplasms per 10,000 person–years.
For five-year survivors, the incidence was twofold higher versus the general population with an excess risk of 35.7 per 10,000 person–years.
The greatest excess risks occurred among survivors of breast cancer (85.8 per 10,000 person–years), lymphomas other than Hodgkin lymphoma or non-Hodgkin lymphoma (82.0 per 10,000 person–years), and oral cavity, lip, and pharyngeal cancer (74.7 per 10,000 person–years).
Conversely, no significant excesses were observed for survivors of acute myeloid leukemia, central nervous system cancers, ovarian cancer, nonovarian and nontesticular gonadal and related tumors, stomach cancer, lung, bronchial, and tracheal cancer, and endometrial cancer.
After five-year survival, the 30-year cumulative incidence of a subsequent primary neoplasm was 17.7% overall, with incidence highest among survivors of cancers of the oral cavity, lip, or pharynx (28.9%), breast cancer (27.3%), colon cancer (23.5%), and Hodgkin lymphoma (22.7%).
Importantly, the team found that the absolute difference in cumulative incidence between the survivors and general population grew as time since diagnosis increased; for example, for five-year survivors of breast cancer, the absolute difference was 2.9% at 10 years postdiagnosis compared with 12.7% at 30 years postdiagnosis.
“Although people with nearly all types of adolescent and young adult cancer investigated were at an increased risk of developing a subsequent primary neoplasm, survivors of Hodgkin lymphoma and breast cancer were identified as particularly vulnerable populations, with nearly one-third of subsequent primary neoplasms occurring after five-year survival diagnosed in these survivor groups,” Fidler-Benaoudia et al remark. “These findings are consistent with previous studies and reflect the established late effects of radiotherapy, chemotherapy, and hormone therapy.”
However, they also note that genetic factors may play a role, and that genetic counseling and education on maintaining healthy lifestyles are important in caring for survivors.
The most common subsequent primary neoplasms were breast (27.1%), digestive (11.9%), hematopoietic (10.6%), or respiratory (6.8%) cancers, together accounting for nearly 60% of subsequent primary neoplasms.
Fidler-Benaoudia and colleagues say that their findings “offer valuable directions for research and cancer control.”
They point out that at present there are no risk-based survivorship care guidelines that cover the entire age range of the adolescent and young adult cancer population.
“Although both pediatric and adolescent and young adult cancer survivors are at increased risks for late effects, the magnitude of these risks varies and implications for care can differ; thus, clinical investigations that assess the association of treatment exposures with late effects like subsequent primary neoplasms should be a research priority,” the authors write.
They also stress that further work is needed to expand inclusion criteria for early high-risk screening initiatives and to develop specialized treatment guidelines that balance curing the subsequent primary neoplasm while effectively managing the survivors’ late effects.
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