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Authors Willemse PM, Burggraaf J, Hamdy NAT, Weijl NI, Vossen CY, van Wulften L, van Steijn-van Tol AQMJ, Rosendaal FR, Osanto S
Review Date June 2013
Citation British Journal of Cancer 2013 May 9. doi: 10.1038/bjc.2013.226 [Epub ahead of print]
Testicular cancer is the second most common cancer in young men, diagnosed in about 750 Australian men each year, and has a very high cure rate. However, testicular cancer patients treated with cisplatin-based chemotherapy or radiotherapy have an increased risk for cardiovascular disease (CVD), which might be related to the increased prevalence of the metabolic syndrome (MetS) in this group of patients.
The purpose of this cross-sectional Dutch study was to examine the relationship between MetS and CVD in three patient groups (surgery patients, carboplatin patients and combination-CT patients) and compare these against healthy controls.
This study assessed the prevalence of MetS and calculated the 10-year CVD risk in a cohort of 255 survivors of testicular germ cell tumours (GCT) originating in the testis (median age= 38.7 years) at a mean of 7.8 years after cancer treatment, compared with 360 healthy men. The GCT survivors were recruited from a Clinical Oncology department between 2008 and 2010. Data for controls were obtained from GP health screening records (from 2009) in the same region.
79 patients had stage-I disease; 58 were treated with orchidectomy alone (‘surgery patients’) and 21 seminoma patients also received one adjuvant dose of carboplatin (AUC7; ‘carboplatin patients’). Patients with disseminated disease (n=176) were treated with orchidectomy and combination chemotherapy (‘combination-CT patients’).
Prevalence of MetS was estimated from the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), 2002 (NCEP-ATPIII) criteria and International Diabetes Federation (IDF) risk score charts. The 10-year cardiovascular risk profile was calculated using Framingham Risk Score (FRS) and the Systemic Coronary Risk Score (SCORE).
There were no major differences in age between the different treatment groups of GCT survivors and the controls. BMI and waist circumference were comparable between the groups. Smoking behaviour was comparable in all groups of patients and the controls, with about 40% smokers. There were no major differences in blood pressure and renal function between the groups.
Combination-CT patients had significantly higher fasting serum concentrations of cholesterol, LDL- cholesterol, and triglyceride than that in controls, and higher serum cholesterol and triglyceride concentrations compared with that in surgery patients. Carboplatin patients had higher fasting serum cholesterol (P=0.04) and LDL-cholesterol (P=0.004) concentrations than that in healthy subjects. Survivors treated with surgery only had higher LDL-cholesterol concentrations than that in healthy subjects (P=0.04).
GCT survivors had an age-adjusted increased odds ratio (OR) for MetS (defined by NCEP-ATPIII) of 1.9 (95% CI=1.1 – 3.2) compared with that of healthy controls. The risk for MetS was highest in GCT survivors treated with combination chemotherapy (OR=2.4, 95% CI=1.4 – 4.1). The risk of MetS was especially increased in survivors with testosterone levels in the lowest quartile (OR=2.5, 95% CI=1.3 – 4.7). Ten-year cardiovascular risk as assessed by the FRS (3.0%) and SCORE (1.7%) algorithms was low, independent of treatment, and was comparable to controls.
Testicular germ cell tumour survivors have an increased prevalence of MetS, with hypogonadism and CT treatment being clear associated risk factors. The increased prevalence of MetS was not associated with an increased 10-year cardiovascular risk. The researchers contend that because hypogonadism is associated with increased cardiovascular risk, GCT survivors should have a lower threshold for testosterone supplementation.
The researchers also advocate that guidelines to monitor blood pressure, lipid- and glucose metabolism, and assessment of gonadal hormone status should be introduced in international urology/oncology guidelines rather than focusing only on the detection of tumour recurrence, allowing for evidence-based counselling of GCT survivors regarding modifiable CVD risk factors.
Points to Note
- As has been shown in other studies, the high prevalence of MetS does not necessarily translate into increased cardiovascular risk.
- It is of particular note that in the study cohort all GCT survivors, but in particular combination-CT survivors, had higher BMI and were significantly more overweight than controls.
- In the GCT survivor population, low testosterone concentrations correlated with MetS and the patients treated with combination CT had a lower testosterone measure than those treated with surgery alone. After adjusting for testosterone, there still was a significant difference in MetS prevalence between the two groups, also after adjusting for age and smoking.
- Different definitions are used for MetS worldwide, and depending on the classification that is used, the prevalence of MetS may vary greatly. Within this study, there was an almost twofold higher absolute MetS prevalence when using IDF (26.9%) compared with using NCEP-ATPIII (14.6%). However, the RR for MetS was shown to be independent of the scoring system.
- This study has a short follow-up period and more longitudinal analysis of this cohort may provide additional details of the relationship between MetS and CVD in GCT survivors.
- The findings of this study may not warrant the changes to guidelines suggested by the authors.