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

• Published in: Cancer Vol. 126; no. 3; pp. 628 - 639
• Main Authors: Groot, Harmke J., Leeuwen, Flora E., Lubberts, Sjoukje, Horenblas, Simon, Wit, Ronald, Witjes, J. Alfred, Groenewegen, Gerard, Poortmans, Philip M., Hulshof, Maarten C. C. M., Meijer, Otto W. M., Jong, Igle J., Berg, Hetty A., Smilde, Tineke J., Vanneste, Ben G. L., Aarts, Maureen J. B., Jóźwiak, Katarzyna, Belt‐Dusebout, Alexandra W., Gietema, Jourik A., Schaapveld, Michael
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.02.2020; John Wiley and Sons Inc
• Subjects: Bladder; Bladder cancer; Cancer; Cardiovascular diseases; cause‐specific mortality; Chemotherapy; cisplatin; Confidence intervals; Coronary artery disease; Dosage; epidemiology; Exposure; Hazard assessment; Health hazards; Health risk assessment; Heart diseases; Ischemia; Kidney cancer; Leukemia; Mortality; Neoplasia; Neoplasms; Oncology; Original; Pancreas; Pancreatic cancer; Platinum; Radiation therapy; Rectum; Seminoma; Stomach; survivorship; Testes; Testicular cancer; testicular cancer; epidemiology; survivorship; cause-specific mortality; platinum; cisplatin
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.32538

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. Platinum‐containing chemotherapy is associated with a dose‐dependent increase in the risk of cancer mortality among patients with testicular cancer. Patients with testicular cancer experience increased mortality from second malignancies as well as causes other than cancer, particularly ischemic heart diseases.