Abstract
BackgroundLate effects of cisplatin-based chemotherapy in testicular cancer survivors (TCS) include cardiovascular morbidity, but little data is available beyond 20 years. The objective was to assess vascular damage in very long-term TCS.MethodsTCS (treated with chemotherapy or orchiectomy only) and age-matched healthy controls were invited. Study assessment included vascular stiffness with ultrasound measurement of carotid-femoral pulse wave velocity (cf-PWV).ResultsWe included 127 TCS consisting of a chemotherapy group (70 patients) and an orchiectomy group (57 patients) along with 70 controls. Median follow-up was 28 years (range: 20–42). The cf-PWV (m/s) was higher in TCS than in controls (geometrical mean 8.05 (SD 1.23) vs. 7.60 (SD 1.21), p = 0.04). The cf-PWV was higher in the chemotherapy group than in the orchiectomy group (geometrical mean 8.39 (SD 1.22) vs. 7.61 (SD 1.21), p < 0.01). In the chemotherapy group cf-PWV increased more rapidly as a function of age compared to controls (regression coefficient b 7.59 × 10−3 vs. 4.04 × 10−3; p = 0.03).ConclusionVery long-term TCS treated with cisplatin-based chemotherapy show increased vascular damage compatible with “accelerated vascular aging” and continue to be at risk for cardiovascular morbidity, thus supporting the need for intensive cardiovascular risk management.Clinical trial registrationThe clinical trial registration number is NCT02572934.
Highlights
Late effects of cisplatin-based chemotherapy in testicular cancer survivors (TCS) include cardiovascular morbidity, but little data is available beyond 20 years
Patients In this analysis we report on two groups of TC survivors—those treated with orchiectomy only and those treated with orchiectomy followed by CT—in comparison with age-matched controls (Fig. 1)
TC survivors were more likely to have hypertension compared to the controls
Summary
Late effects of cisplatin-based chemotherapy in testicular cancer survivors (TCS) include cardiovascular morbidity, but little data is available beyond 20 years. Successful treatment is often accompanied by adverse late treatment effects, resulting in increased morbidity from second cancers,[5] cardiovascular disease (CVD),[6,7,8,9,10] nephrotoxicity,[11,12] pulmonary toxicity[13] and Raynaud’s phenomenon.[14,15] Many of these late treatment effects of CT may be different manifestations of the same underlying vascular damage, possibly induced directly by cisplatin-based CT or indirectly by increased CVD risk factors after CT.[16,17] This increased morbidity coincides with increased long-term mortality: patients treated with CT for TC had a 1.6-fold (95% CI = 1.0–2.5) higher risk of dying from CVD compared to the general population 10 years after treatment.[18] An alarming clinical feature is the relatively young age at which TC survivors develop CVD,[8,10] which led to the hypothesis that TC patients treated with CT show a phenotype resembling accelerated aging.[9,19,20] the mechanisms underlying this cardiovascular morbidity have not been extensively studied.[21] In addition, most data on the incidence of late effects have been collected through questionnaires in large epidemiological studies in TC survivors up to 15 years post-treatment
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