Long-term cardiovascular complications in stage I seminoma patients
Long-term cardiovascular complications in stage I seminoma patients
A. Terbuch 0 1 2 3 4 5
F. Posch 0 1 2 3 4 5
L. M. Annerer 0 1 2 3 4 5
T. Bauernhofer 0 1 2 3 4 5
M. Pichler 0 1 2 3 4 5
J. Szkandera 0 1 2 3 4 5
G. C. Hutterer 0 1 2 3 4 5
K. Pummer 0 1 2 3 4 5
R. Partl 0 1 2 3 4 5
K. S. Kapp 0 1 2 3 4 5
H. Sto¨ ger 0 1 2 3 4 5
A. Gerger 0 1 2 3 4 5
M. Stotz 0 1 2 3 4 5
0 Research Unit Genetic Epidemiology and Pharmacogenetics, Medical University of Graz , Graz , Austria
1 Division of Clinical Oncology, Department of Internal Medicine, Medical University of Graz , Auenbruggerplatz 15, 8036 Graz , Austria
2 Department of Therapeutic Radiology and Oncology, Medical University of Graz , Graz , Austria
3 Department of Urology, Medical University of Graz , Graz , Austria
4 Department of Experimental Therapeutics, The University of Texas, MD Anderson Cancer Center , Houston , USA
5 Center for Biomarker Research in Medicine (CBmed) , Graz , Austria
Purpose The cure rate of stage I seminoma patients is close to 100% and so the recent focus of clinical research has shifted onto the prevention of treatment-related complications. We assessed long-term cardiovascular complications and identified risk factors for cardiovascular events (CVEs) in stage I seminoma patients. Methods This retrospective cohort study included 406 consecutive stage I seminoma patients. Primary endpoint was CVE rate. Results During a median follow-up of 8.6 years, we observed 23 CVEs in 406 patients [10-year CVE risk 5.6% (95% CI 3.2 to 8.8)]. In univariable competing risk analysis, higher age, positive smoking status, history of diabetes and hypertension were significantly associated with the occurrence of CVE. In multi-state analysis, new onset of diabetes, hypertension and hyperlipidemia during follow-up predicted for an excessively increased CVE risk. In multivariable analysis adjusting for age and smoking, the development of hypertension and hyperlipidemia after tumor-specific treatment prevailed as risk factors for CVE. Regarding adjuvant treatment modalities, patients receiving adjuvant radiotherapy had a significantly higher probability of CVE than patients receiving adjuvant carboplatin [16% vs. 0%; risk difference (RD) = 16%, 95% CI 6 to 25%, p = 0.001]. This difference prevailed after adjusting for age, follow-up-time, diabetes, hypertension and smoking (RD = 11%, 95% CI 1 to 20%, p = 0.025). Conclusion We identified a panel of baseline risk factors and dynamically, occurring predictors of CVE in stage I seminoma patients. This information may be used for targeting comorbidity management in these patients. The observed association of adjuvant radiotherapy with higher CVE risk warrants further investigation.
Testicular cancer; Seminoma; Cardiovascular risk; Radiotherapy; Carboplatin; Active surveillance
Introduction
Seminoma constitutes 40% of all testicular cancers and
about 80 to 85% of patients are diagnosed with clinical
stage I (CS I) disease. Active surveillance, adjuvant
chemotherapy with one single cycle of carboplatin (at a
dose of 7 9 area under curve) or adjuvant radiotherapy to
paraaortic lymph nodes are treatment options for stage I
seminoma [
1, 2
]. Regardless of treatment strategy, the cure
rate is close to 100% even in case of relapse and so the
recent focus of clinical research has shifted onto the
prevention of treatment-related complications [
3–5
].
Radiotherapy and chemotherapy have both been
associated with an increased risk of long-term cardiovascular
complications when compared with the general population
[
6–10
]. Chemotherapy causes endothelial damage and
might, therefore, increase the risk of cardiovascular events
[
11–13
]. In case of radiotherapy, it has been suggested that
cardiac toxicity might be related to renal
hypertension/diabetes mellitus secondary to partial kidney/pancreatic
irradiation by the para-aortic field [
6, 14
]. In this
retrospective cohort study, we tried to identify risk factors for
the occurrence of cardiovascular complications in stage I
seminoma patients and looked for differences regarding the
three adjuvant treatment modalities, and potential
interaction with general cardiovascular risk factors.
Methods and patients
Patient population
All consecutive patients (n = 950) with histologically
confirmed TGCT, presenting to the Division of Oncology
at the Medical University of Graz between January 1994
and December 2013, were retrospectively reviewed. Out
of the 950 patients, 406 (44.9%) men had a tumor with
seminomatous histology and CS I and were included in
this retrospective cohort study. Patients were initially
staged using computed tomographic (CT) scans of the
abdomen, CT scan or X-ray of the chest and postoperative
tumor markers a-fetoprotein (AFP), human chorionic
gonadotropin (HCG) and lactate dehydrogenase (LDH).
Tumor markers within normal limits after orchiectomy
and the absence of metastases on imaging defined CS I.
Postoperative management options were (...truncated)