Platinum exposure and cause-specific mortality among patients with testicular cancer

Cancer. 2020 Feb 1;126(3):628-639. doi: 10.1002/cncr.32538. Epub 2019 Nov 15.

Abstract

Background: Although testicular cancer (TC) treatment has been associated with severe late morbidities, including second malignant neoplasms (SMNs) and ischemic heart disease (IHD), cause-specific excess mortality has been rarely studied among patients treated in the platinum era.

Methods: In a large, multicenter cohort including 6042 patients with TC treated between 1976 and 2006, cause-specific mortality was compared with general population mortality rates. Associations with treatment were assessed with proportional hazards analysis.

Results: With a median follow-up of 17.6 years, 800 patients died; 40.3% of these patients died because of TC. The cumulative mortality was 9.6% (95% confidence interval [CI], 8.5%-10.7%) 25 years after TC treatment. In comparison with general population mortality rates, patients with nonseminoma experienced 2.0 to 11.6 times elevated mortality from lung, stomach, pancreatic, rectal, and kidney cancers, soft-tissue sarcomas, and leukemia; 1.9-fold increased mortality (95% CI, 1.3-2.8) from IHD; and 3.9-fold increased mortality (95% CI, 1.5-8.4) from pneumonia. Seminoma patients experienced 2.5 to 4.6 times increased mortality from stomach, pancreatic, bladder cancer and leukemia. Radiotherapy and chemotherapy were associated with 2.1 (95% CI, 1.8-2.5) and 2.5 times higher SMN mortality (95% CI, 2.0-3.1), respectively, in comparison with the general population. In a multivariable analysis, patients treated with platinum-containing chemotherapy had a 2.5-fold increased hazard ratio (HR; 95% CI, 1.8-3.5) for SMN mortality in comparison with patients without platinum-containing chemotherapy. The HR for SMN mortality increased 0.29 (95% CI, 0.19-0.39) per 100 mg/m2 platinum dose administered (Ptrend < .001). IHD mortality was increased 2.1-fold (95% CI, 1.5-4.2) after platinum-containing chemotherapy in comparison with patients without platinum exposure.

Conclusions: Platinum-containing chemotherapy is associated with a dose-dependent increase in the risk of SMN mortality.

Keywords: cause-specific mortality; cisplatin; epidemiology; platinum; survivorship; testicular cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antineoplastic Agents / therapeutic use
  • Cause of Death
  • Cisplatin / adverse effects
  • Cisplatin / therapeutic use
  • Cohort Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms, Second Primary / drug therapy*
  • Neoplasms, Second Primary / mortality*
  • Neoplasms, Second Primary / pathology
  • Neoplasms, Second Primary / radiotherapy
  • Platinum / therapeutic use
  • Proportional Hazards Models
  • Risk Factors
  • Survivorship
  • Testicular Neoplasms / drug therapy*
  • Testicular Neoplasms / mortality*
  • Testicular Neoplasms / pathology
  • Testicular Neoplasms / radiotherapy
  • Young Adult

Substances

  • Antineoplastic Agents
  • Platinum
  • Cisplatin