Long-term outcomes of adolescents and young adults with testicular germ cell tumors: A population-based retrospective matched cohort study.

Abstract

12016 Background: Testicular germ cell tumor (TGCT) survival exceeds 90%, but survivors of adult TGCT are at risk of developing late effects. Little is known about the risk for late effects in survivors of TGCT in children, adolescents, or young adults (CAYA). Methods: We identified all CAYA aged 11-21 years at TGCT diagnosis in Ontario, Canada, between 1992-2021. Those with complete treatment records were matched 1:5 by birth date and postal code at diagnosis to individuals from the general population (controls). Controls’ index date was defined as the diagnosis date of their survivor match. Participants were linked to health administrative databases to identify second malignant neoplasms (SMN); cardiovascular disease (CVD: congestive heart failure [CHF], myocardial infarction, coronary artery disease, pericardial disease, valvular abnormalities, arrhythmia, stroke, hypertension); renal disease (dialysis, kidney transplant); and hearing loss (physician-diagnosed hearing loss, hearing aid use). Cumulative incidences were compared between survivors and controls, and between chemotherapy and surgery treated survivors using Gray’s test. Cox proportional hazard models compared the risk of late effects between survivors and controls. Results: 521 TGCT survivors (296 chemotherapy treated, 225 treated with surgery only) were matched to 2605 controls. Median age at diagnosis/index date was 19 years. Survivors’ median follow-up time was 14.8 years (interquartile range: 10.7-21.7). Compared to controls, survivors had higher 15-year incidence and hazard ratio (HR) of all SMN (5.0% vs 0.5%; HR 8.4, p < .0001), non-testicular SMN (2.1% vs 0.5%; HR 3.8, p = 0.0003), dialysis (1.0% vs 0.04%; HR 12.4, p = 0.003), kidney transplant (0.4% vs 0.0%, p = 0.002), hearing loss (7.1% vs 3.1%; HR 1.8, p = 0.005), and hearing aid use (1.0% vs 0.2%; HR 4.1, p = 0.02). Survivors were at substantially increased risk of any CVD (8.2% vs 5.5%; HR 1.4, p < 0.03), CHF (1.2% vs. 0.2%; HR 5.0, p = 0.006), arrhythmia (1.8% vs 0.5%; HR 3.4, p = 0.002), and stroke (0.8% vs 0.05%; HR 8.7, p = 0.0006) despite no anthracycline exposure. Compared to surgery only treated survivors, chemotherapy treated survivors had higher 15-year incidence of any CVD (13.1% vs 2.0%, p < 0.0001), CHF (2.1% vs 0.0%, p = 0.03), arrhythmia (3.3% vs 0.0%, p = 0.02), stroke (1.4% vs 0.0%, p = 0.02), hypertension (7.4% vs 2.0%, p = 0.009), and hearing loss (10.2% vs 3.0%, p = 0.02). Conclusions: Survivors of TGCT during CAYA are at considerable risk for late effects affecting multiple organ systems. In addition to previously described morbidities like hearing loss, survivors (particularly those who received chemotherapy) are at higher risk of CVD. Despite excellent rates of cure, TGCT survivors diagnosed at a young age require life-long risk-directed follow-up to maximize their long-term health.