Thromboembolic Events During Treatment with Cisplatin-based Chemotherapy in Metastatic Testicular Germ-cell Cancer 2000–2014: A Population-based Cohort Study

Abstract

Background

Cisplatin-based chemotherapy (CBCT) in testicular cancer (TC) is associated with elevated venous thromboembolism (VTE) risk, but trials evaluating the safety and efficacy of thromboprophylaxis are lacking.

Objective

To evaluate the arterial thromboembolism (ATE) and VTE incidence and risk factors during first-line CBCT for metastatic TC, and the effect of thromboprophylaxis on VTE and bleeding.

Design, setting, and participants

In a population-based study, 506 men administered first-line CBCT during 2000–2014 at three university hospitals in Norway were included. Clinical variables were retrieved from medical records.

Outcome measurements and statistical analysis

Patients with ATE and VTE diagnosed at initiation of or during CBCT until 3 mo after completion were registered. Age-adjusted logistic regression was performed to identify possible VTE risk factors.

Results and limitations

Overall, 69 men (13.6%) were diagnosed with 70 thromboembolic events. Twelve men (2.4%) experienced ATE. Overall, 58 men (11.5%) experienced VTE, of whom 13 (2.6%) were prevalent at CBCT initiation, while 45 (8.9%) were diagnosed with incident VTE. Age-adjusted logistic regression identified retroperitoneal lymph node metastasis >5 cm (odds ratio [OR] 1.99, 95% confidence interval [CI] 1.01–3.91), central venous access (OR 2.84, 95% CI 1.46–5.50), and elevated C-reactive protein (>5 mg/l; OR 2.38, 95% CI 1.12–5.07) as incident VTE risk factors. Thromboprophylaxis ( n = 84) did not influence the risk of VTE (VTE incidence with or without prophylaxis 13% vs 8%, p = 0.16). The incidence of bleeding events was significantly higher among those who received thromboprophylaxis than among those without thromboprophylaxis (14.5% vs 1.1%, p < 0.001).

Conclusions

We found a high rate of thromboembolism incidence of 13.6%. Thromboprophylaxis did not decrease the risk of VTE but was associated with an increased risk of bleeding.

Patient summary

We found a high rate of thromboembolism (13.6%) during cisplatin-based chemotherapy for metastatic testicular cancer. Prophylactic treatment against thromboses did not reduce the thrombosis frequency, but it resulted in a high incidence of bleeding events.

Take Home Message

We found a high rate of thromboembolism (13.6%) during cisplatin-based chemotherapy for metastatic testicular cancer. Prevalent venous thromboembolism (VTE) was more frequent in men with retroperitoneal lymph nodes >5 cm, intermediate/poor prognosis disease, poor performance status, and elevated C-reactive protein. Consequently, we advise to examine these patients closely with regard to VTE.

Central venous access and large retroperitoneal lymph node metastases were associated with an increased risk of incident VTE in age-adjusted analysis. Patients without any risk factors had 5% incidence of VTE, indicating a thrombotic potential of cisplatin-based chemotherapy. Prophylactic treatment against thromboses did not reduce the thrombosis frequency, but it resulted in a high incidence of bleeding events.