Annals of Oncology Advance Access originally published online on January 17, 2007
Annals of Oncology 2007 18(2):211-212; doi:10.1093/annonc/mdl480
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© 2007 European Society for Medical Oncology
editorials |
Follow-up of successfully treated testicular cancer patients: consequences of the metabolic syndrome
Department of Medical Oncology, University Medical Center Groningen, University of Groningen, The Netherlands
* E-mail: j.a.gietema{at}int.umcg.nl
The first reports on the long-term follow-up of testicular cancer patients, including long-term treatment-related toxicity, originate from the late 1980s. Several of these papers report on cardiovascular disease, in particular myocardial infarction and coronary artery disease, after treatment with cisplatin-based chemotherapy [1–3]. With prolonged follow-up and a growing number of these survivors, there is increasing evidence that both chemotherapy and radiotherapy are associated with an increased long-term risk of cardiovascular disease, compared with treatment with orchidectomy only [4–6] and with the general male background population [6, 7]. Development of cardiovascular disease together with secondary malignancies belongs to the most important long-term risks for successfully treated testicular cancer patients [6, 8]. Since the risk of cardiovascular disease seems to be particular high at younger age, the development of cardiovascular disease might represent an important threat to life expectancy and quality of life [6].
Insight into the mechanisms underlying the development of cardiovascular disease after treatment of testicular cancer may contribute to identification of useful targets for intervention. One of the suggested mechanisms is endothelial dysfunction with early atherosclerosis, of which signs are found in testicular cancer survivors treated with cisplatin-based chemotherapy [9]. It is unknown whether the unfavourable influence of chemotherapy on the cardiovascular risk is caused by a direct effect on the vasculature or by an indirect effect, for example, secondary to the development of cardiovascular risk factors.
Since the observation that testicular cancer survivors show an increase in serum cholesterol levels after cisplatin-based chemotherapy [10], several studies on long-term complications have focussed on the prevalence of cardiovascular risk factors, particularly dyslipidaemia, obesity and hypertension [7, 11–13]. These three cardiovascular risk factors represent, together with insulin resistance, the core components of the so-called metabolic syndrome. The metabolic syndrome consists of a combination of cardiovascular risk factors that co-exist more frequently than expected by chance alone. Although the aetiology of this syndrome is unknown, there is evidence that it is associated with an increased risk of cardiovascular morbidity and mortality [14]. This association may render the metabolic syndrome a useful tool to identify persons at increased risk for cardiovascular disease and a target for therapy in clinical practice.
The metabolic syndrome appears to be present in successfully treated testicular cancer patients [15]. Its potential importance is underlined by the article of Haugnes et al. [16] on the metabolic syndrome in long-term testicular cancer survivors, in this issue of the Annals of Oncology.
Haugnes et al. examined the association between the different treatment modalities for testicular cancer [two chemotherapy groups (cumulative cisplatin dose 
850 mg and cumulative cisplatin dose >850 mg), radiotherapy and surgery] and the metabolic syndrome in a large cohort of 1135 testicular cancer survivors. Haugnes et al. show that testicular cancer survivors treated with cisplatin-based chemotherapy, have an increased risk of developing the metabolic syndrome and that its prevalence is negatively associated with total serum testosterone levels. Lower odds were, however, found for the metabolic syndrome in the surgery group, compared with healthy controls. This differs from the data from Nuver et al. [15], who found that stage I patients also have more often a metabolic syndrome. This discrepancy may be partially due to differences in the applied definition. Haugnes et al. applied a modified definition, containing components of different definitions for the metabolic syndrome, formulated by the World Health Organisation (WHO) [17] and The European Group for the Study of Insulin Resistance (EGIR) [18], whereas the earlier report by Nuver et al. used the definition by The National Cholesterol Education Program—Third Adult Treatment Panel (NCEP ATP III) [19]. The use of different definitions for the metabolic syndrome, of which the definitions by the WHO, EGIR and NCEP ATP III are the most widely accepted and used, hampers the comparison between studies on its prevalence.
Regardless of the differences in the applied definitions, the observation of Haugnes et al. underlines the risk of development of cardiovascular risk factors in clusters such as the metabolic syndrome after successful treatment of testicular cancer.
After being treated successfully, a patient with testicular cancer is currently followed 5 years, 10 years or even lifelong by an oncologist [20–22]. However, more than 15 years after the observation of Boyer that elevated serum cholesterol after chemotherapy, might serve as risk factor for future development of cardiovascular disease, none of the recent treatment and follow-up guidelines for testicular cancer patients includes details on how to monitor and treat cardiovascular risk factors [20–22]. In our opinion, accumulating data support the need to address this issue to ensure early detection and, if necessary, treatment of cardiovascular risk factors such as clustered in the metabolic syndrome. In accordance with other groups of cancer survivors, guidelines are needed on the follow-up, including monitoring for late effects of cancer treatment in collaboration with primary care professionals [23, 24].
This implies that the follow-up after successful treatment of testicular cancer, in addition to the early detection of relapse, should be extended with special attention to early detection of metabolic syndrome-like clusters and associated features such as decreased testosterone levels, lifestyle and tobacco smoking [25]. During the follow-up, the oncologist should check for occurrence of cardiovascular risk factors. In case of ending the follow-up, a testicular cancer survivor and his primary care physician should receive an end-of-treatment summary in which the possibilities of developing cardiovascular risk factors such as the metabolic syndrome are described.
In the meantime, research on prospective standardised follow-up of the metabolic syndrome and its components in testicular cancer survivors is warranted and may produce information about its aetiology, the sequence and moment of its development and its predictive value for cardiovascular disease in this specific group. More insight into these kinds of long-term complications will contribute to evidence-based follow-up guidelines with details on how and when to monitor for the metabolic syndrome and associated features. In addition, such research may contribute to the development of prevention and intervention strategies, specifically adjusted to the testicular cancer survivor. For example, the suppletion of testosterone may in future prove to modulate the underlying mechanism of the metabolic syndrome in this group of survivors. Such an approach should be addressed in a randomised controlled trial.
Until data specific for testicular cancer survivors is available, the metabolic syndrome can be treated according to strategies from the general population, consisting of healthy lifestyle promotion and pharmacological therapy of its separate components [26]. In future, guidelines for standardised follow-up, prevention and treatment of cardiovascular risk factors such as the metabolic syndrome and its associated features may contribute to improvement of the life expectancy of successfully treated testicular cancer patients.
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