Late effects are a source of long term cardiovascular and pulmonary morbidity in testicular cancer (TC) survivors. The objective was to assess vascular damage and pulmonary function in TC survivors more than 20 years after cisplatin-bleomycin combination CT and compare this to age-matched patients treated for TC with surgery only (SU) as well as healthy male controls (CO).
Aortic stiffness was measured by the gold standard of aortic pulse-wave velocity (aPWV) from the carotid to femoral artery. aPWV is considered an accurate predictor of cardiovascular risk. Additional blood markers for vascular damage were assessed, including factor VIII, v-WF and fibrinogen. Pulmonary function including Diffusion Capacity Carbon Monoxide (DLCO) was assessed according to international guidelines using spirometry, body-plethysmography and the single breath-holding method parameters.
After a mean follow-up duration of 28 years (range: 20-42), aPWV and DLCO was assessed in 118 TC survivors (63 CT patients and 55 SU patients) and 56 controls. aPWV (m/s) was higher in the CT group as compared to the SU and CO group (geometric mean 8.49 vs 7.69 and 7.64 respectively, P = 0.005). DLCO (% predicted) was significantly reduced in CT patients compared to SU patients (87% vs 94%, P = 0.02).A significant reduction in DLCO (defined as < 80% of predicted) occurred in 27% and 13% for CT and SU patients, respectively (X2; P = 0.055). In the CT patient group, aPWV and DLCO were associated (r = 0.3, P = 0.03). Furthermore, in the CT patient group, DLCO and endothelial activation markers were associated (vWF r=-0.30, P = 0.02; F-VIII r=-0.31, P = 0.01; fibrinogen r=-0.27, P = 0.03).
TC survivors treated with cisplatin-bleomycin combination chemotherapy have an increased aortic stiffness and reduced DLCO more than 20 years after treatment. This implicates an increased risk of cardiovascular morbidity and impaired pulmonary function. Association between markers for vascular damage and reduced DLCO suggests a role of vascular damage in the etiology of pulmonary dysfunction for TC survivors.
Clinical trial identification
Legal entity responsible for the study
University Medical Center Groningen, The Netherlands (PI: Prof. Dr. J.A. Gietema).
Dutch Cancer Society, Grant no. RUG2011-5267.
J.A. Gietema: Research funding to institute: Roche, Abbvie, Siemens. All other authors have declared no conflicts of interest.