Microalbuminuria, decreased fibrinolysis, and inflammation as early signs of atherosclerosis in long-term survivors of disseminated testicular cancer

doi:10.1016/j.ejca.2003.12.012

European Journal of Cancer

Volume 40, Issue 5, March 2004, Pages 701-706

https://doi.org/10.1016/j.ejca.2003.12.012 Get rights and content

Abstract

Testicular cancer patients have an increased risk for coronary artery disease more than ten years after cisplatin-based chemotherapy. We investigated whether vascular changes, including endothelial dysfunction, are present earlier. Ninety chemotherapy-treated testicular cancer patients (median follow-up of seven years) were compared with 44 patients after orchidectomy only and 47 healthy men. Microalbuminuria was present in 10 (12%) chemotherapy patients, one stage I patient and none of the controls. Chemotherapy patients had higher levels of fibrinogen, C-reactive protein (hs-CRP), von Willebrand factor (vWF), plasminogen activator inhibitor (PAI-1), and tissue-type plasminogen activator (t-PA). Chemotherapy patients with elevated PAI-1 (25/90) showed clustering of cardiovascular risk factors resembling the metabolic syndrome. In conclusion, cured testicular cancer patients showed a high prevalence of microalbuminuria and increased plasma levels of endothelial and inflammatory marker proteins, which might progress to more severe endothelial dysfunction and overt atherosclerosis.

Introduction

Testicular cancer is the most common malignancy in men between 20 and 40 years of age. Over recent decades, the number of survivors of disseminated testicular cancer has increased, due to an increase in incidence and a decrease in mortality as a result of the introduction of cisplatin- and bleomycin-containing chemotherapy. Testicular cancer patients are assumed to have a normal life expectancy once they reach a durable complete remission. However, several studies have demonstrated treatment-related factors that may affect morbidity and mortality in the long term.

Cardiovascular complications of standard chemotherapy have been reported in testicular cancer patients several years after treatment. Cardiovascular risk factors, like hypertension, hypercholesterolaemia, overweight 1, 2, 3, and insulin resistance [4] occur frequently. Furthermore, recent studies have demonstrated an increased risk for cardiovascular events ten or more years after cisplatin- and bleomycin-containing chemotherapy 4, 5.

Endothelial damage is thought to play an important role in the development of late vascular toxicity following chemotherapy for testicular cancer. In vitro studies have provided some clues for the existence of both bleomycin- and cisplatin-induced endothelial damage 6, 7. Furthermore, Raynaud's phenomenon, occurring in up to 37% following bleomycin- and cisplatin-containing chemotherapy [2], has been associated with endothelial dysfunction.

While an increased risk of cardiovascular events has been established in testicular cancer patients more than ten years after chemotherapy, it is unknown whether atherosclerotic changes are present earlier. Early detection of vascular changes is important for early therapeutic intervention with the aim to reduce cardiovascular risk. We performed a cross-sectional study to investigate whether atherosclerotic changes, endothelial dysfunction in particular, are present in cured testicular cancer patients after cisplatin-based chemotherapy. Chemotherapy-treated patients were compared with stage I testicular cancer patients who had not received chemotherapy, but had been treated with orchidectomy only and with healthy men of comparable age.

Section snippets

Patients

All patients with disseminated non-seminomatous testicular cancer who had been successfully treated with cisplatin-containing chemotherapy at the University Hospital Groningen, The Netherlands, between July 1988 and April 1999 were approached to participate. Radiotherapy, a history of cardiovascular events before diagnosis, and age above 55 years at the start of chemotherapy were exclusion criteria. Patients with stage I non-seminomatous testicular cancer, free of disease after orchidectomy

Results

Ninety chemotherapy patients (89% of 101 eligible patients), 44 stage I patients with a similar follow-up, and 47 healthy male controls participated (Table 1).

Discussion

Patients with disseminated testicular cancer have an increased risk for cardiovascular disease more than ten years after chemotherapy 4, 5. We investigated whether signs of atherosclerosis are present earlier. We found a high prevalence of microalbuminuria and high levels of markers of inflammation and endothelial activation in testicular cancer patients after a median follow-up of only seven years.

Microalbuminuria, an indicator of generalised endothelial dysfunction [12], was present in 12% of

Conflict of interest statement

No conflicts of interest.

Acknowledgments

Supported by grant RUG2000-2177 from the Dutch Cancer Society.

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Microalbuminuria, decreased fibrinolysis, and inflammation as early signs of atherosclerosis in long-term survivors of disseminated testicular cancer

Abstract

Introduction

Section snippets

Patients

Results

Discussion

Conflict of interest statement

Acknowledgments

Atherosclerosis

Lancet

Eur. Urol.

Ultrasound Med. Biol.

Am. J. Cardiol.

Long-term follow-up of cardiovascular risk factors in patients given chemotherapy for disseminated nonseminomatous testicular cancer

Ann. Intern. Med.

Evaluation of long-term toxicity after chemotherapy for testicular cancer

J. Clin. Oncol.

Excessive annual BMI increase after chemotherapy among young survivors of testicular cancer

Br. J. Cancer

Cardiovascular morbidity in long-term survivors of metastatic testicular cancer

J. Clin. Oncol.

Cardiovascular disease as a long-term complication of treatment for testicular cancer

J. Clin. Oncol.

Release of cytokines from human umbilical vein endothelial cells treated with platinum compounds in vitro

Jpn. J. Cancer Res.