Survival After Secondary Primary Malignant Neoplasms Significantly Poorer in Children and AYAs versus Older Patients

Second cancers are deadlier in patients under age 40 than in older adults

An analysis of more than one million cancer patients of all ages revealed that a diagnosis of second primary malignant neoplasms (SPMs) carries a far greater risk of death from cancer for children or adolescents and young adults (AYAs) than older adults.

AYAs that experienced a second Hodgkin lymphoma (HL), sarcoma, or breast, thyroid, or testicular cancer faced a risk of cancer-specific death that was increased by more than 2-fold over a cohort of similarly aged patients with no prior history of cancer who were diagnosed with the same cancers.

Among patients in all age groups, patients had an 80% chance of 5-year survival after diagnosis of the first cancer. However, when the same cancer type reappeared as an SPM, the 5-year survival rate dropped to 47% in children, and 60% in AYAs.

This study was recently published online in JAMA Oncology.

First author Theresa H. M. Keegan, PhD, of the Center for Oncology Hematology Outcomes Research and Training, Division of Hematology and Oncology, University of California, Davis, School of Medicine, Sacramento, USA and colleagues wrote that data from studies comparing survival in the same cancers diagnosed as an SPM with those diagnosed as first primary malignant neoplasm (PM) according to age were lacking, although an increased incidence of SPMs is a well documented late effect following cancer.

Better survival was observed across all age groups when the cancer occurred as a primary versus a secondary malignancy

In order to determine the impact of SPMs on survival in AYAs, a research team in the United States (US) compared the survival risk following diagnosis of an SPM in children, AYAs, and older adults. The investigators reviewed 13 US regions contained in the Surveillance, Epidemiology and End Results (SEER) database to identify patients diagnosed with cancer from 1992 to 2008 who were followed through 2013. Analysis of data compiled in this population-based, retrospective cohort study was performed between June 2016 and January 2017. The analysis evaluated the impact of SPMs on survival in AYAs aged 15 to 39 years as compared with paediatric patients aged <15 years and older adult patients aged ≥40 years patients and with patients in the same age groups experiencing the same cancers as a primary malignant neoplasm.

This analysis used multivariable Cox proportional hazards regression on data from 15’954 paediatric, 125’750 AYAs, and 878’370 older adult patients who were diagnosed with 14 types of cancer either as a PM or SPM.

Patients diagnosed with cancer as a SPM showed poorer survival outcomes as compared to patients with the same cancer that occurred as a PM; furthermore, these survival differences were greater in patients aged 39 and younger.

Patients with a SPM had a 5-year survival following diagnosis that was decreased by 33.1% in children, 20.2% in AYAs, and by 8.3% in older adults compared with similarly aged patients diagnosed with the same cancers as a PM.

Poorer survival in AYAs was consistent across several cancer types

The investigators stratified the data according to the most commonly occurring SPMs, including secondary non-Hodgkin lymphoma (NHL), secondary breast carcinoma, secondary thyroid carcinoma, secondary soft-tissue sarcoma (STS), HL, acute myeloid leukaemia (AML), and central nervous system (CNS) cancer.

A comparison of survival according to age in patients with SPMs revealed that younger patients had a significantly worse outcome for thyroid, HL, NHL, AML, STS, and CNS cancer than older patients with the same secondary cancers.

The investigators found an absolute difference in 5-year survival in AYAs with SPMs versus PMs that was 42% decreased for secondary NHL, 19% for secondary breast carcinoma, 15% for secondary thyroid carcinoma, and 13% for secondary STS.

Across the types of cancer studied, the AYA population did worse with a secondary cancer. The hazard ratios (HR) for risk of death from cancer in AYAs with an SPM versus AYAs with the same cancer diagnosed as a PM were higher: in secondary HL the HR was 3.5 (95% confidence interval [CI] 1.7, 7.1), STS, HR 2.8 (95% CI 2.1, 3.9), secondary breast carcinoma, HR 2.1 (95% CI 1.8, 2.4), AML HR 1.9 (95%CI 1.5, 2.4), and CNS cancer, HR 1.8 (95%CI 1.2, 2.8) experienced worse survival compared with AYAs with the same PMs.


The authors wrote that the greater adverse impact of a SPM on survival seen in children and AYAs may partially explain the relative lack of survival improvement in AYAs compared with other age groups. These findings suggest that the impact of a particular SPM diagnosis on survival may inform age-specific prevention, screening, treatment, and survivorship recommendations.


Keegan THM, Bleyer A, Rosenberg AS, et al. Second Primary Malignant Neoplasms and Survival in Adolescent and Young Adult Cancer Survivors. JAMA Oncol. Published online April 20, 2017. doi:10.1001/jamaoncol.2017.0465