Second Cancers May Be Deadlier in Child, Adolescent, and Young Adult Patients

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Second cancers in children and adolescents and young adults (AYAs) are far deadlier than they are in older adults and may partially account for the relatively poor outcomes of cancer patients between the ages of 15 and 39 overall, a new study by researchers at the University of California, Davis has found.

The study also found that survival after almost all types of cancer is much higher when the cancer occurs as a primary malignancy than as a second cancer, and these survival differences are most pronounced in patients younger than age 40. The findings were published by Keegan et al in JAMA Oncology.1

Theresa Keegan, PhD

Theresa Keegan, PhD

Based on an analysis of more than 1 million cancer patients of all ages from throughout the United States, the study is the first to compare survival after a second cancer to survival of the same cancer that occurs as the first primary malignancy, by age. Researchers hope the findings help guide clinicians in providing age-specific recommendations on cancer prevention, screening, treatment, and survivorship, especially among the AYA population, for whom survival rates have not improved to the same extent as they have for children and older adults.

“Although the increased incidence of second cancers is well known among cancer survivors, less is known about outcomes of these cancers or the influence of age,” said Theresa Keegan, PhD, a cancer epidemiologist at the University of California Davis Comprehensive Cancer Center and the study’s lead author. “Second cancers are a serious late effect of having a prior cancer and, for most cancers, have a substantial impact on survival.”

Study Findings

Dr. Keegan and colleagues identified all patients diagnosed with only one or a first and second malignancy during 1992 through 2008 using Surveillance, Epidemiology, and End Results (SEER) program data collected from 13 cancer registries. The researchers were careful not to capture recurrences of the same cancer when identifying secondary malignancies.

The authors collected data on the 14 most common cancer types that affect AYAs: female breast, thyroid, testicular, Hodgkin lymphoma, non-Hodgkin lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, soft-tissue sarcoma, bone sarcoma, colorectal, central nervous system, cervical, and ovarian.

Overall, children and AYAs had an 80% chance of surviving 5 years after a diagnosis of a first cancer. But if the same cancer occurred as a secondary malignancy, 5-year survival dropped to 47% for children and 60% for the AYA population. The differences in survival were not nearly as marked in the older adult population, who had a 70% chance of surviving 5 years overall for a first cancer and 61% for a new, second malignancy.

When the researchers looked at 5-year survival by age and individual cancer types, they found striking differences depending on whether it was a first or secondary malignancy in all but 2 of the 14 cancer types—testicular and melanoma.

“For almost every type of cancer, the AYA population did worse with a secondary cancer,” said Melanie Goldfarb, MD, an endocrine surgeon at John Wayne Cancer Institute and coauthor on the study. “What struck us was that the second cancer caused such an increased risk of death.”

For almost every type of cancer, the AYA population did worse with a secondary cancer. What struck us was that the second cancer caused such an increased risk of death.
— Melanie Goldfarb, MD

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For example, AYA patients diagnosed with acute myeloid leukemia as a first cancer had a 57% chance of surviving for 5 years, but that dropped to 29% if it was the second cancer. For AYA patients diagnosed with breast cancer, the 5-year survival was 81% for a first cancer but 63% if it was a second cancer.

Why younger patients tend to fare worse than older patients with the same second cancers is not fully understood or specifically addressed in the current study, the authors said. Dr. Keegan said a possible explanation for worse outcomes may be that those with a secondary cancer have a worse response to treatment, limitations on the types or doses of treatments they can receive as a result of their prior cancer treatment, or impaired physiologic reserves that impact their ability to tolerate treatment.

Dr. Goldfarb added that psychosocial issues may play an important role or combine with other factors such as an underlying biologic condition that predisposes someone to cancer.

“These younger people don’t have all the support or resources they need,” she added. “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.”

The authors plan next to examine how the time between getting a first and second cancer affects survival and whether the type of treatment for the first cancer influences the outcome of a second cancer. ■

Disclosure: For full disclosures of the study authors, visit


1. Keegan THM, Bleyer A, Rosenberg AS, et al: Second primary malignant neoplasms and survival in adolescent and young adult cancer survivors. JAMA Oncol. April 20, 2017 (early release online).