Predicting Cardiovascular Disease Among Testicular Cancer Survivors After Modern Cisplatin-based Chemotherapy: Application of the Framingham Risk Score

Clin Genitourin Cancer. 2018 Aug;16(4):e761-e769. doi: 10.1016/j.clgc.2018.01.011. Epub 2018 Feb 5.

Abstract

Background: Testicular cancer survivors (TCSs) are at increased risk of cardiovascular disease (CVD) after cisplatin-based chemotherapy (CBCT). Identifying at-risk survivors would allow early intervention, but risk prediction tools such as the Framingham Risk Score (FRS) have not been applied to TCSs given modern chemotherapy.

Methods: TCSs > 1 year post-CBCT were evaluated. Associations between FRS and clinical, socioeconomic, and lifestyle measures and treatment regimen (4 cycles, etoposide and cisplatin [EP × 4]); 3 or 4 cycles, bleomycin plus EP (BEP × 3, BEP × 4) were analyzed with general linear multivariable models. Controls from the National Health and Nutrition Examination Survey were matched 1:1 to TCSs by age, race, and education with differences in mean FRS evaluated with 2-sided t tests.

Results: Of 787 TCSs (median age, 37.3 years; median follow-up, 4.2 years), 284, 342, and 161 received EP × 4, BEP × 3, or BEP × 4, respectively. TCSs had higher median systolic blood pressure (126 vs. 119 mm Hg; P < .001), but fewer were smokers (8.4% vs. 28.2%; P < .001) than controls. In multivariable analysis, no significant differences in FRS between EP × 4, BEP × 3, and BEP × 4 were observed, but less than college education (P < .001) and lack of vigorous exercise (P = .006) were associated with higher FRS. Mean FRS did not differ between TCSs and controls (6.8% vs. 7.3%; P = .67).

Conclusion: This is the first study to apply the office-based FRS to TCSs. Chemotherapy regimen (BEP × 3 vs. EP × 4) was not associated with FRS, but less educated and less vigorously active patients had higher FRS, and present a high-risk subgroup for intense follow-up and counseling.

Keywords: Cytotoxic drugs; Germ cell tumor; Late effects; NHANES controls; Risk model.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bleomycin / adverse effects
  • Bleomycin / therapeutic use
  • Cancer Survivors
  • Cardiovascular Diseases / chemically induced*
  • Cardiovascular Diseases / epidemiology*
  • Cisplatin / adverse effects
  • Cisplatin / therapeutic use
  • Etoposide / adverse effects
  • Etoposide / therapeutic use
  • Humans
  • Male
  • Middle Aged
  • Risk Factors
  • Testicular Neoplasms / drug therapy*
  • Young Adult

Substances

  • Bleomycin
  • Etoposide
  • Cisplatin