What is the clinical evidence from this study?

Study design: Cohort. Population: Testicular germ cell tumors (TGCT) (n=1277). Intervention: Cisplatin-based chemotherapy vs. No cisplatin-based chemotherapy. Primary outcome: Arterial thromboembolic events (ATE) within 1 year (95% CI 0.5-2.5, p=0.003).

February 14, 2025Open Access

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

Q: What does this research mean for the field?

Arterial thromboembolic events occur in 12.0% of testicular cancer patients at 25 years and are independently associated with a significantly increased risk of all-cause mortality. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Key Result

Arterial thromboembolic events occurred in 12.0% of testicular cancer patients at 25 years and were independently associated with a significantly increased risk of all-cause mortality (HR 4.61).

Study Design

Type

Cohort (n=1,277)

Multicenter

Structured PICO

What is the incidence, impact on mortality, and risk factors for arterial thromboembolic events in patients with testicular germ cell tumors?

Population

1277 patients with testicular germ cell tumors (TGCT) treated between 1994 and 2020, median age 35 years, 56% seminoma, 44% received cisplatin-based chemotherapy.

Intervention

Cisplatin-based chemotherapy and clinical risk factors (age ≥ 35, smoking, and lactate dehydrogenase ≥ 250 IU/L)

Comparator

No cisplatin-based chemotherapy and lower risk strata

Outcome

Arterial thromboembolic events (ATE) defined as acute coronary syndrome, ischemic stroke, and acute peripheral arterial occlusioncomposite

Arterial thromboembolic events are a common long-term complication in testicular cancer survivors, are associated with increased mortality, and can be risk-stratified using a simple point-based score.

Main Result

Absolute Event Rate: 1.3% vs 0%

p-value: p=0.003

Limitations

Retrospective study design might affect the quality of follow-up data
No comparative effect estimates of ATE risk in TGCT patients compared with the general population due to the lack of an adequate control group
Variables included in risk factor evaluations were limited by data availability, precluding the assessment of novel biomarkers or established cardiovascular risk scores
Medical comorbidities at study inclusion were defined based on treating physicians and might be subject to misdiagnoses
Longitudinal changes in risk factors and health behavior were not assessed
Decreases in sample sizes over the duration of long-term follow-up led to lower statistical precision for late time points

Abstract

BACKGROUND: Patients with testicular germ cell tumors (TGCT) have a high cancer-specific survival rate. OBJECTIVES: 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 and 2020 were included in a single-center retrospective cohort study. The primary outcome was ATE (ie, acute coronary syndrome, ischemic stroke, and acute peripheral arterial occlusion). Cumulative incidences were obtained in competing risk analysis. The impact of ATE on mortality was analyzed in a multistate model. Cox regression was used to explore short- and long-term ATE risk factors. RESULTS: Overall, 1277 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% CI, 0.3%-1.1%), 2.6% (95% CI, 1.8%-3.7%), and 12.0% (95% CI, 8.7%-15.9%), respectively. ATE diagnosis was independently associated with increased all-cause mortality (age-adjusted transition hazard ratio, 4.61; 95% CI, 2.40-8.85; P < .001). Cisplatin-based chemotherapy was associated with ATE risk within 1 year after TGCT diagnosis (1.4% vs 0%, P < .001), whereas no differences were observed thereafter. Regarding long-term ATE risk, a point-based risk score was derived (age ≥ 35, smoking, and lactate dehydrogenase ≥ 250 IU/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. CONCLUSION: ATE represents a common complication in TGCT survivors and is associated with increased mortality. A simple point-based score efficiently stratifies long-term ATE risk, whereas cisplatin-based chemotherapy increases short-term ATE risk.

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