Second Cancers Produce Poorer Survival Outcomes in Young Adults

The substantial adverse impact of second cancers may explain the lack of improvement in young adult survival compared with older adults.

Second cancer occurrence in children, adolescents, and young adults is far deadlier than in older adults, according to a study published in JAMA Oncology.

For the study, the authors sought to examine the survival impact of second primary malignant neoplasms (SPMs) in adolescents and young adults aged 15 to 39 years compared with pediatric patients younger than 15 years and older adults 40 years and older with the same SPMs.

Included in the retrospective cohort study were patients with cancer in 13 Surveillance, Epidemiology and End Results regions in the United States diagnosed between 1992 and 2008, and followed through 2013.

The 5-year relative survival was calculated overall, and for each cancer that occurred as a primary malignancy (PM) or SPM by age at diagnosis. To examine the impact of SPM status on cancer-specific death, the investigators used multivariable Cox proportional hazards regression.

In total, the study included 15,954 pediatric patients, 125,750 young adult patients, and 878,370 older adult patients who were diagnosed as having 14 cancers occurring as a PM or SPM.

The results showed that the 5-year survival after an SPM was 33.1% lower for children, 20.2% lower for young adults, and 8.3% lower for older adults compared with a PM at the same age.

“Although the increased incidence of second cancers is well known among cancer survivors, less is known about the outcomes of these cancers or the influence of age,” said lead author Theresa Keegan. “Second cancers are a serious late effect of having a prior cancer and, for most cancers, have a substantial impact on survival.”

For the most common SPMs in young adults, the absolute difference in 5-year survival was 42% lower for secondary non-Hodgkin lymphoma, 19% for secondary breast carcinoma, 15% for secondary thyroid carcinoma, and 13% for secondary soft-tissue sarcoma.

Adolescents and young adults with secondary Hodgkin lymphoma, soft tissue sarcoma, breast carcinoma, acute myeloid leukemia (AML), and central nervous system cancer had worse survival outcomes compared with young adults with the same PMs.

“For almost every type of cancer, the [young adult] population did worse with a secondary cancer,” said co-author Melanie Goldfarb. “What struck us was that the second cancer caused such an increased risk of death.”

Young adult patients diagnosed with AML as a first cancer had a 57% chance of surviving 5 years, but that dropped to 29% if it was the second cancer. Furthermore, in young adult patients diagnosed with breast cancer, the 5-year survival was 81% for the first cancer and 63% if it was the second cancer.

The authors noted that although it remains unclear why young patients tend to do worse than older patients with the same second cancers, one possible explanation could be that those with a secondary cancer have a worse response to treatment, limitations in treatments due to their prior cancer treatment, or impaired physiologic reserves that impacts treatment tolerability. Additionally, psychosocial issues may also play a role.

“These younger people don’t have all the support or resources they need,” she said. “They may not have adequate insurance, or they may get lost in the system. They may suffer from depression, which can contribute to their overall health and worsen their cancer outcome.”

Next, the authors plan to investigate the time it takes between getting first and second cancer and the impact on survival, as well as whether the type of treatment for the first cancer influences the outcome of the second cancer.