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Long-Term Risk of Cardiovascular Disease in 5-Year Survivors of Testicular Cancer

From the Departments of Epidemiology, Radiotherapy, and Medical Oncology, the Netherlands Cancer Institute; Department of Radiotherapy, Academic Medical Center Amsterdam, Amsterdam; Department of Medical Oncology, Erasmus Medical Center-Daniel den Hoed Cancer Center, Rotterdam; the Department of Medical Oncology, University Medical Center Groningen, Groningen; and the Department of Radiotherapy, Dr Bernard Verbeeten Institute, Tilburg, the Netherlands

Address reprint requests to Flora E. van Leeuwen, PhD, Department of Epidemiology, the Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; e-mail: f.v.leeuwen{at}nki.nl

Purpose To evaluate the long-term risk of cardiovascular disease (CVD) in survivors of testicular cancer (TC).

Patients and Methods We compared CVD incidence in 2,512 5-year survivors of TC, who were treated between 1965 and 1995, with general population rates. Treatment effects on CVD risk were quantified in multivariate Cox regression analysis.

Results After a median follow-up of 18.4 years, 694 cardiovascular events occurred, including 141 acute myocardial infarctions (MIs). The standardized incidence ratio (SIR) for coronary heart disease was 1.17 (95% CI, 1.04 to 1.31), with 14 excess cases per 10,000 person-years. The SIR for MI was significantly increased in nonseminoma survivors with attained ages of less than 45 (SIR = 2.06) and 45 to 54 years (SIR = 1.86) but significantly decreased for survivors with attained ages of 55 years or older (SIR = 0.53). In Cox analysis, mediastinal irradiation was associated with a 3.7-fold (95% CI, 2.2- to 6.2-fold) increased MI risk compared with surgery alone, whereas infradiaphragmatic irradiation was not associated with an increased MI risk. Cisplatin, vinblastine, and bleomycin (PVB) chemotherapy (CT) was associated with a 1.9-fold (95% CI, 1.7- to 2.0-fold) increased MI risk, and bleomycin, etoposide, and cisplatin (BEP) CT was associated with a 1.5-fold (95% CI, 1.0- to 2.2-fold) increased CVD risk and was not associated with increased MI risk (hazard ratio = 1.2; 95% CI, 0.7 to 2.1). Recent smoking was associated with a 2.6-fold (95% CI, 1.8- to 3.9-fold) increased MI risk.

Conclusion Nonseminomatous TC survivors experience a moderately increased MI risk at young ages. Physicians should be aware of excess CVD risk associated with mediastinal radiotherapy, PVB CT, and recent smoking. Intervention in modifiable cardiovascular risk factors is especially important in TC survivors. Whether BEP treatment increases CVD risk should be evaluated after more prolonged follow-up.

Supported by the Lance Armstrong Foundation and the Dutch Cancer Society.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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