Arterial thromboembolic events in testicular cancer patients: Short- and long-term incidence, risk factors and impact on mortality.

Abstract

Background: Patients with testicular germ cell tumors (TGCT) have a high cancer-specific survival rate. We aimed to determine the short- and long-term risk of arterial thromboembolic events (ATE), their impact on mortality, and risk factors for ATE in TGCT patients.

Methods: Patients with TGCT treated between 1994-2020 were included in a single-center retrospective cohort study. The primary outcome was ATE (i.e., acute coronary syndrome, ischemic stroke, acute peripheral arterial occlusion). Cumulative incidences were obtained in competing risk analysis. The impact of ATE on mortality was analyzed in a multi-state model. Cox-regression was used to explore short-and long term ATE-risk factors.

Results: Overall, 1,277 patients were included (median age: 35 years; seminoma: 56%, 44% cisplatin-based chemotherapy). Cumulative ATE-incidences at 1-, 10-, and 25-years were 0.6% (95% confidence interval [CI]: 0.3-1.1), 2.6% (1.8-3.7), and 12.0% (8.7-15.9). ATE diagnosis was independently associated with increased all-cause mortality (age-adjusted transition hazard ratio: 4.61 [95%CI: 2.40-8.85], p<0.001). Cisplatin-based chemotherapy was associated with ATE-risk within 1 year after TGCT diagnosis (1.4% vs 0%, p<0.001), whereas no differences were observed thereafter. Regarding long-term ATE-risk, a point-based risk score was derived (age ≥35, smoking, LDH ≥250IU/L), which efficiently stratified ATE risk (Harrel´s C: 0.71 [95% CI: 0.63-0.78]), with cumulative ATE-incidences in low-, intermediate- and high-risk patients of 3.9%, 11.4%, and 22.7%, respectively.

Conclusions: ATE represent a common complication in TGCT survivors and are associated with increased mortality. A simple point-based score efficiently stratifies long-term ATE-risk, whereas cisplatin-based chemotherapy increased short-term ATE risk.