Survivorship after Testicular Cancer in Adolescents and Young Adults- What is Causing Death and When?

Abstract

Testicular germ cell tumor (GCT) is the most common malignancy among adolescent and young adult (AYA) males, yet long-term causes of death beyond primary cancer are not well defined. We evaluated cause-specific mortality in AYA survivors of testicular GCT to identify patterns across histology, stage, and throughout survivorship. This is a population-based analysis using SEER data. Standardized mortality ratios (SMRs) compared observed causes of death among AYA patients with GCT to expected rates in age-, sex-, and year-matched controls. Of 1,870 deaths, 52% were from primary GCT, 15% from non-testis cancers (SMR 4.13), and 32% from non-cancer causes (SMR 1.11). Non-cancer deaths occurred at higher-than-expected rates for chronic liver disease/cirrhosis but were lower for heart disease. Non-seminoma was associated with higher GCT mortality and modestly elevated mortality from liver disease and diabetes.Stage I patients most often died from accidents/suicide/homicide, whereas stage III patients experienced markedly elevated secondary cancer mortality. Mortality patterns shifted over time: GCT deaths predominated in years 0-5; accidents/suicide/homicide, cardiovascular, and liver disease were elevated early. After 10 years, non-cancer deaths predominated but were below expected rates. Limitations include retrospective design, potential misclassification of cause of death, and inability to assess treatment-specific exposures. AYA testicular GCT survivors experience substantial non-cancer and secondary malignancy mortality, with risks varying by histology, stage, and time since diagnosis. Survivorship care should incorporate behavioral health support, comprehensive health monitoring, and secondary cancer surveillance.