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

Harmke J Groot, Flora E van Leeuwen, Sjoukje Lubberts, Simon Horenblas, Ronald de Wit, J Alfred Witjes, Gerard Groenewegen, Philip M Poortmans, Maarten C C M Hulshof, Otto W M Meijer, Igle J de Jong, Hetty A van den Berg, Tineke J Smilde, Ben G L Vanneste, Maureen J B Aarts, Katarzyna Jóźwiak, Alexandra W van den Belt-Dusebout, Jourik A Gietema, Michael Schaapveld*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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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.

Original languageEnglish
Pages (from-to)628-639
Number of pages12
JournalCancer
Volume126
Issue number3
Early online date15-Nov-2019
DOIs
Publication statusPublished - 1-Feb-2020

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