Second Primary Malignancies More Deadly in Younger Cancer Patients

Younger cancer survivors experience worse survival outcomes following a second primary malignancy diagnosis than their older counterparts, according to a study published recently in JAMA Oncology. This was seen in both pediatric patients as well as adolescent and young adult (AYA) patients. The study also found a more pronounced reduction in survival for patients under 40 when a cancer occurs as a secondary malignancy vs a primary cancer.

“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 lead study author Theresa Keegan, PhD, a cancer epidemiologist at the UC Davis Comprehensive Cancer Center in Sacramento, California, in a press release.

Researchers conducted a population-based, retrospective cohort study of patients diagnosed with either one or two primary cancers between 1992 to 2008 using the Surveillance, Epidemiology, and End Results (SEER) database. Patients were followed through 2013. Fourteen different types of cancer were diagnosed among the patients studied, including lymphoma, leukemia, sarcoma, breast cancer, thyroid cancer, and central nervous system (CNS) tumors, among others.

A total of 15,954 pediatric patients (< 15 years of age), 125,750 AYA patients (15–39 years of age), and 878,370 older adult patients (≥ 40 years of age) were included in the study.

Compared with outcomes for a primary cancer at the same age, the 5-year survival after a secondary primary cancer diagnosis was 33.1% lower for children, 20.2% lower for AYAs, and 8.3% lower for older adults. For example, AYAs diagnosed with acute myeloid leukemia as a first cancer had a 57% chance of surviving for 5 years, but that decreased to 29% if it was their second primary malignancy.

Among the most common secondary primary malignancies in AYAs, the absolute difference in 5-year survival was 42% lower for non-Hodgkin lymphoma, 19% lower for breast cancer, 15% lower for thyroid cancer, and 13% lower for soft-tissue sarcoma compared with primary cancers diagnosed at the same age.

Survival after a second primary cancer appeared to be much worse in younger vs older patients with regard to acute myeloid leukemia, soft-tissue sarcoma, thyroid cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, and CNS cancers. Children and AYAs had an 80% chance of surviving 5 years after a primary cancer diagnosis, but if the same cancer occurred as a secondary cancer, the 5-year survival rate dropped to 47% for children and 60% for AYAs. Older adult patients had a 70% chance of surviving 5 years after a first cancer diagnosis and 61% after a second primary cancer diagnosis.

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

Why the AYA population may fare worse compared with older patients is not fully understood. A few reasons could be that younger patients may not respond to treatment as well the second time around, dose limitations due to already receiving treatment for a primary cancer, biological factors, or even psychosocial issues (lack of insurance, mental health issues).

Considering secondary primary cancer survival rates have not improved among the AYA population, researchers hope that these kinds of studies will help guide clinicians on age-specific recommendations when it comes to cancer prevention, screening, treatment, and survivorship.