Physical morbidities in survivors of testicular germ cell tumors during childhood, adolescence, and young adulthood: a population-based retrospective matched cohort study

Background — While testicular germ cell tumors (TGCT) survival exceeds 90%, many survivors of adult TGCT are at risk for treatment toxicities. Less is known about physical morbidities in children, adolescents, and young adults (CAYA) with TGCT.

Methods — We used the Pediatric Oncology Group of Ontario Networked Information System, the Initiative to Maximize Progress in Adolescent and Young Adult Cancer Therapy, and the Ontario Cancer Registry to identify all CAYA males diagnosed with TGCT from 1992 to 2021 at age 11–21 years in Ontario, Canada. We matched patients at TGCT diagnosis (one-to-five ratio) to cancer-free males from the general Ontario population who were identified from the Registered Person Database. We linked CAYA to health administrative databases to identify subsequent malignant neoplasms (SMN) and hearing loss/aid use after TGCT diagnosis. We assessed cardiovascular disease (CVD), dialysis, and kidney transplant that occurred <five years (early effect) and ≥five years (late effect) from TGCT diagnosis. We used the cumulative incidence function and cause-specific hazard models.

Findings — We identified 748 patients (404 chemotherapy-treated) and 3740 controls. Median age at diagnosis was 19.0 years [interquartile range (IQR): 18.0–21.0] and 29.7 years (IQR: 25.0–37.6) at the end of follow-up. Chemotherapy-treated patients had higher risk than controls for non-TGCT SMN [hazard ratio (HR) = 4.5, 95% CI: 1.8–11.4], hearing loss/aid (HR = 2.7, 95% CI: 1.8–4.2), early dialysis (HR = 7.7, 95% CI: 1.3–46.8), any early CVD (HR = 7.3, 95% CI: 4.1–13.0), and any late CVD (HR = 1.6, 95% CI: 1.1–2.4), particularly late stroke (HR = 7.4, 95% CI: 1.2–44.6). Compared to their controls, non-chemotherapy-treated patients had higher risk for late dialysis (HR = 10.5, 95% CI: 1.1–103.8), and lower risk for late hypertension (HR = 0.4, 95% CI: 0.2–1.0). Non-chemotherapy-treated patients had higher cumulative incidence of second contralateral TGCT than chemotherapy-treated patients (15-year incidence = 4.6% vs. 0.9%, p = 0.0049).

Interpretation — Chemotherapy-treated CAYA with TGCT are at elevated risks for non-TGCT SMN, hearing loss, and early CVD compared to the general population. The long latency for certain outcome risks indicate further research is needed to characterize the health outcomes of these survivors as they age.