# Thromboembolic disease in testicular germ cell tumors—real-world evidence of three Portuguese institutions

## TL;DR

This study examines thromboembolic events in testicular germ cell tumors, finding they occur mainly in advanced cases and are linked to tumor burden and catheter use.

## Contribution

The study provides real-world evidence on thromboembolic events in TGCT and identifies risk factors not captured by existing prediction models.

## Key findings

- Thromboembolic events occurred in 5.1% of patients, all in advanced or recurrent disease.
- Visceral metastases and poor IGCCCG prognosis were associated with thromboembolic events.
- Current risk prediction models like Khorana and ONKOTEV did not predict TE in this cohort.

## Abstract

Testicular germ cell tumors (TGCTs) are highly curable malignancies with long-term overall survival (OS) exceeding 90%. Thromboembolic (TE) events are a relevant treatment-related complication, reported in approximately 10% of patients. This study aimed to evaluate the incidence, risk factors, and prognostic impact of TE in TGCT.

We performed a retrospective multicenter cohort study including 136 post-pubertal male patients with histologically confirmed TGCT treated between 2007 and 2021 at three Portuguese centers. The primary endpoint was to characterize the population of TGCT patients with TE. Secondary endpoints included TE incidence and its impact on OS and progression-free survival (PFS). Identification of clinical, pathological, and treatment-related factors associated with increased TE risk was an exploratory endpoint.

Seven patients (5.1%) developed a TE event, all in advanced/recurrent disease (14.6% in this subgroup). No TE occurred in stage I patients, including those treated with adjuvant chemotherapy. Visceral metastases (pulmonary and extra-pulmonary) and poor IGCCCG prognosis were associated with TE (p < 0.05). All TE patients had a central venous catheter (CVC), although only two had catheter-related thrombosis (p = 0.019). For advanced stages, survival outcomes did not differ significantly, with 5-year OS of 71.4% vs. 86.2% (p = 0.22) and PFS of 47.6% vs. 75.5% (p = 0.23) in TE versus non-TE groups, respectively. Most events (86%) occurred within 30 days of chemotherapy initiation, with pulmonary embolism as the most frequent presentation. Neither the Khorana nor the ONKOTEV scores predicted TE.

TE in TGCT occurred only in patients with advanced disease, was linked to tumor burden and CVC use, and was not predicted by current models. These findings highlight the need for TGCT-specific risk tools and prospective studies on risk-adapted prophylaxis.