Vascular aging in long-term survivors of testicular cancer more than 20 years after treatment with cisplatin-based chemotherapy

Abstract

Background: Late 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.

Methods: TCS (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).

Results: We 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).

Conclusion: Very 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 registration: The clinical trial registration number is NCT02572934.

Conflict of interest statement

J.A.G. received grants from Abbvie, Roche and Siemens, paid to the institution. All other authors declare no competing interests.

Figures

Fig. 1. Consort diagram.

The institutional database of testicular cancer patients was used to identify testicular cancer survivors (TCS) treated with chemotherapy (CT). Patients were randomly selected and screened for inclusion. Eligible CT patients were approached if they were still alive and met the inclusion criteria:

Fig. 2. Pulse wave velocity (cf-PWV) for all TC survivors (TCS), controls (CO) and for separate study groups.

Pulse wave velocity (cf-PWV) as biomarker for vascular stiffness for all TC survivors (TCS), controls (CO) and for separate study groups. Bars represent median values and interquartile range. Corresponding geometrical means are reported. P values were obtained by students T-test of the logarithmic transformation.

Fig. 3. Pulse wave velocity (cf-PWV) as biomarker for vascular stiffness as a function of age for the chemotherapy (CT) group and the control group.

Orange line represents the CT group and blue line the control group. Corresponding linear regression lines were based on regression coefficients for age calculated in the multivariate model correcting for other predictive variables. ∆cf-PWV at age 70 amounts to 2.03 m/s. For CT: 10(0.475 + (7.590 × 10–3 × Age)). For CO: 10(0.627 + (4.035 ×10–3 × Age)). Slopes differ significantly (p = 0.03).

Fig. 4. Raynaud Phenomenon tested by cooling digits.

Mean number of digits with perfusion at each time point during PPG-test. The first 36 min represent the cooling period. Next, 10 min of recovery time at room temperature is shown. Mean ischaemic and recovery times for each study group are reported in Supplementary Table 3.