Testicular Cancer in the Cisplatin Era: Causes of Death and Mortality Rates in a Population-Based Cohort
Ragnhild Hellesnes, Tor Åge Myklebust, Sophie D. Fosså, Roy M. Bremnes, Ása Karlsdottir, Øivind Kvammen, Torgrim Tandstad, Tom Wilsgaard, Helene F. S. Negaard, Hege S. Haugnes
Abstract
PURPOSE: Using complete information regarding testicular cancer (TC) treatment burden, this study aimed to investigate cause-specific non-TC mortality with impact on previous treatment with platinum-based chemotherapy (PBCT) or radiotherapy (RT). METHODS: Overall, 5,707 men identified by the Cancer Registry of Norway diagnosed with TC from 1980 to 2009 were included in this population-based cohort study. By linking data with the Norwegian Cause of Death Registry, standardized mortality ratios (SMRs), absolute excess risks (AERs; [(observed number of deaths - expected number of deaths)/person-years of observation] ×10,000), and adjusted hazard ratios (HRs) were calculated. RESULTS: Median follow-up was 18.7 years, during which non-TC death was registered for 665 (12%) men. Overall excess non-TC mortality was 23% (SMR, 1.23; 95% CI, 1.14 to 1.33; AER, 11.14) compared with the general population, with increased risks after PBCT (SMR, 1.23; 95% CI, 1.07 to 1.43; AER, 7.68) and RT (SMR, 1.28; 95% CI, 1.15 to 1.43; AER, 19.55). The highest non-TC mortality was observed in those < 20 years at TC diagnosis (SMR, 2.27; 95% CI, 1.32 to 3.90; AER, 14.42). The most important cause of death was non-TC second cancer with an overall SMR of 1.53 (95% CI, 1.35 to 1.73; AER, 7.94), with increased risks after PBCT and RT. Overall noncancer mortality was increased by 15% (SMR, 1.15; 95% CI, 1.04 to 1.27; AER, 4.71). Excess suicides appeared after PBCT (SMR, 1.65; 95% CI, 1.01 to 2.69; AER, 1.39). Compared with surgery, increased non-TC mortality appeared after 3 (HR, 1.47; 95% CI, 0.91 to 2.39), 4 (HR, 1.41; 95% CI, 1.01 to 1.99), and more than four (HR, 2.04; 95% CI, 1.25 to 3.35) cisplatin-based chemotherapy cycles after > 10 years of follow-up. CONCLUSION: TC treatment with PBCT or RT is associated with a significant excess risk of non-TC mortality, and increased risks emerged after more than two cisplatin-based chemotherapy cycles after > 10 years of follow-up.