Cardiovascular Disease Mortality After Chemotherapy or Surgery for Testicular Nonseminoma: A Population-Based Study

J Clin Oncol. 2015 Oct 1;33(28):3105-15. doi: 10.1200/JCO.2014.60.3654. Epub 2015 Aug 3.

Abstract

Purpose: Increased risks of incident cardiovascular disease (CVD) in patients with testicular cancer (TC) given chemotherapy in European studies were largely restricted to long-term survivors and included patients from the 1960s. Few population-based investigations have quantified CVD mortality during, shortly after, and for two decades after TC diagnosis in the era of cisplatin-based chemotherapy.

Patients and methods: Standardized mortality ratios (SMRs) for CVD and absolute excess risks (AERs; number of excess deaths per 10,000 person-years) were calculated for 15,006 patients with testicular nonseminoma reported to the population-based Surveillance, Epidemiology, and End Results program (1980 to 2010) who initially received chemotherapy (n=6,909) or surgery (n=8,097) without radiotherapy and accrued 60,065 and 81,227 person-years of follow-up, respectively. Multivariable modeling evaluated effects of age, treatment, extent of disease, and other factors on CVD mortality.

Results: Significantly increased CVD mortality occurred after chemotherapy (SMR, 1.36; 95% CI, 1.03 to 1.78; n=54) but not surgery (SMR, 0.81; 95% CI, 0.60 to 1.07; n=50). Significant excess deaths after chemotherapy were restricted to the first year after TC diagnosis (SMR, 5.31; AER, 13.90; n=11) and included cerebrovascular disease (SMR, 21.72; AER, 7.43; n=5) and heart disease (SMR, 3.45; AER, 6.64; n=6). In multivariable analyses, increased CVD mortality after chemotherapy was confined to the first year after TC diagnosis (hazard ratio, 4.86; 95% CI, 1.25 to 32.08); distant disease (P<.05) and older age at diagnosis (P<.01) were independent risk factors.

Conclusion: This is the first population-based study, to our knowledge, to quantify short- and long-term CVD mortality after TC diagnosis. The increased short-term risk of CVD deaths should be further explored in analytic studies that enumerate incident events and can serve to develop comprehensive evidence-based approaches for risk stratification and application of preventive and interventional efforts.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents / adverse effects*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / mortality*
  • Cause of Death
  • Humans
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasms, Germ Cell and Embryonal / diagnosis
  • Neoplasms, Germ Cell and Embryonal / mortality
  • Neoplasms, Germ Cell and Embryonal / therapy*
  • Orchiectomy / adverse effects*
  • Orchiectomy / mortality
  • Proportional Hazards Models
  • Risk Assessment
  • Risk Factors
  • SEER Program
  • Testicular Neoplasms / diagnosis
  • Testicular Neoplasms / mortality
  • Testicular Neoplasms / therapy*
  • Time Factors
  • Treatment Outcome
  • United States / epidemiology

Substances

  • Antineoplastic Agents

Supplementary concepts

  • Nonseminomatous germ cell tumor