TY - JOUR
T1 - Platinum exposure and cause-specific mortality among patients with testicular cancer
AU - Groot, Harmke J.
AU - van Leeuwen, Flora E.
AU - Lubberts, Sjoukje
AU - Horenblas, Simon
AU - de Wit, Ronald
AU - Witjes, J. Alfred
AU - Groenewegen, Gerard
AU - Poortmans, Philip M.
AU - Hulshof, Maarten C. C. M.
AU - Meijer, Otto W. M.
AU - de Jong, Igle J.
AU - van den Berg, Hetty A.
AU - Smilde, Tineke J.
AU - Vanneste, Ben G. L.
AU - Aarts, Maureen J. B.
AU - Jozwiak, Katarzyna
AU - van den Belt-Dusebout, Alexandra W.
AU - Gietema, Jourik A.
AU - Schaapveld, Michael
N1 - Funding Information:
This work was supported by the Dutch Cancer Society (grant 2011‐5209).
Publisher Copyright:
© 2019 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - 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/m
2 platinum dose administered (P
trend <.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.
AB - 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/m
2 platinum dose administered (P
trend <.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.
KW - cause-specific mortality
KW - cisplatin
KW - epidemiology
KW - platinum
KW - survivorship
KW - testicular cancer
UR - https://www.scopus.com/pages/publications/85075205019
U2 - 10.1002/cncr.32538
DO - 10.1002/cncr.32538
M3 - Article
C2 - 31730712
SN - 0008-543X
VL - 126
SP - 628
EP - 639
JO - Cancer
JF - Cancer
IS - 3
ER -